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h
84.224 776.746 m
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h
85.8 776.988 m
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86.487 775.348 86.525 775.59 86.525 775.788 c
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85.8 776.988 l
h
88.467 775.907 m
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89.678 774.752 89.719 774.629 y
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88.708 773.913 88.467 773.951 88.346 773.951 c
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88.467 775.907 l
h
90.326 775.71 m
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90.285 776.027 90.406 776.347 90.568 776.627 c
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91.899 776.746 91.779 776.627 91.741 776.548 c
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91.699 775.628 91.779 775.468 91.82 775.348 c
91.899 775.188 92.061 775.031 92.224 774.949 c
92.306 774.949 92.386 774.871 92.465 774.871 c
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92.91 774.83 93.072 774.871 93.155 774.871 c
93.234 774.908 93.355 774.99 93.438 775.069 c
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93.355 774.193 93.114 774.07 92.872 774.032 c
92.627 773.951 92.386 773.913 92.182 773.913 c
92.023 773.913 91.861 773.951 91.699 773.951 c
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90.971 774.312 90.73 774.551 90.568 774.83 c
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90.326 775.71 l
h
95.011 775.669 m
95.294 776.306 l
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96.022 777.547 l
96.142 777.547 96.304 777.465 96.467 777.346 c
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94.245 774.39 94.324 774.472 94.366 774.472 c
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95.011 775.669 l
h
96.184 775.389 m
96.266 775.389 96.346 775.43 y
96.346 775.468 96.304 775.59 96.225 775.71 c
96.142 775.829 96.063 775.948 96.022 775.989 c
95.984 776.068 95.901 776.109 95.859 776.109 c
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95.618 775.628 l
95.577 775.549 l
95.577 775.43 l
95.659 775.389 95.739 775.389 v
96.184 775.389 l
f*
62.751 782.494 m
64.816 783.084 l
62.946 783.998 l
62.978 784.36 l
65.695 783.008 l
63.642 782.417 l
65.567 781.489 l
62.647 780.62 l
62.679 780.984 l
64.681 781.565 l
62.751 782.494 l
h
65.574 787.367 m
63.807 787.212 l
63.972 787.562 l
65.306 787.675 l
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65.717 787.67 l
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66.647 786.873 l
65.574 787.367 l
h
66.226 791.601 m
66.582 792.036 l
66.701 792.181 66.831 792.306 66.972 792.413 c
67.125 792.521 67.284 792.599 67.449 792.644 c
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68.339 789.91 l
66.226 791.601 l
h
66.68 791.669 m
68.312 790.364 l
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66.68 791.669 l
h
70.767 796.057 m
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72.439 794.575 l
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70.767 796.057 l
h
71.162 795.431 m
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72.157 794.762 l
71.162 795.431 l
h
76.274 798.458 m
77.542 796.743 l
77.77 798.792 l
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76.506 797.604 l
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76.051 796.348 l
76.274 798.458 l
h
81.311 799.125 m
83.197 796.864 l
83.338 798.851 l
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81.589 798.29 l
81.447 796.288 l
81.112 796.312 l
81.311 799.125 l
h
86.804 797.988 m
87.126 797.884 l
86.286 795.329 l
85.964 795.432 l
86.804 797.988 l
h
90.579 793.643 m
90.367 793.308 l
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89.039 794.283 88.984 794.527 88.994 794.79 c
89.002 795.021 89.066 795.231 89.185 795.42 c
89.206 795.453 89.219 795.474 89.225 795.484 c
89.308 795.614 89.406 795.724 89.521 795.814 c
89.627 795.896 89.748 795.962 89.881 796.011 c
90.131 796.1 90.369 796.126 90.595 796.091 c
90.821 796.056 91.013 795.989 91.172 795.891 c
91.393 795.754 91.561 795.582 91.674 795.375 c
91.464 795.043 l
91.381 795.304 91.224 795.506 90.992 795.649 c
90.91 795.699 90.825 795.737 90.738 795.762 c
90.651 795.787 90.559 795.8 90.462 795.8 c
90.273 795.801 90.091 795.756 89.915 795.664 c
89.74 795.572 89.605 795.453 89.513 795.306 c
89.396 795.122 89.334 794.932 89.326 794.736 c
89.316 794.546 89.355 794.365 89.443 794.194 c
89.488 794.108 89.54 794.031 89.6 793.964 c
89.661 793.898 89.732 793.839 89.815 793.788 c
89.84 793.772 l
90.043 793.647 90.289 793.603 90.579 793.643 c
h
94.176 792.73 m
93.749 793.215 l
93.983 793.416 l
95.056 792.196 l
94.822 791.995 l
94.395 792.48 l
92.577 790.918 l
92.358 791.168 l
94.176 792.73 l
h
97.551 788.271 m
96.061 786.739 l
98.143 786.873 l
98.298 786.543 l
95.26 786.371 l
96.74 787.897 l
94.604 787.75 l
96.692 789.945 l
96.848 789.614 l
95.409 788.121 l
97.551 788.271 l
h
98.729 782.13 m
98.716 782.28 98.677 782.415 98.612 782.534 c
98.547 782.653 98.459 782.759 98.345 782.852 c
98.232 782.945 98.106 783.013 97.967 783.054 c
97.823 783.099 97.677 783.115 97.531 783.102 c
97.337 783.085 97.159 783.022 96.997 782.911 c
96.835 782.8 96.713 782.659 96.63 782.486 c
96.547 782.314 96.514 782.132 96.53 781.94 c
96.548 781.748 96.612 781.574 96.725 781.417 c
96.837 781.26 96.981 781.141 97.158 781.061 c
97.335 780.98 97.522 780.948 97.72 780.965 c
97.873 780.978 98.016 781.019 98.148 781.086 c
98.272 781.147 98.382 781.233 98.477 781.346 c
98.568 781.451 98.636 781.571 98.681 781.708 c
98.726 781.843 98.742 781.984 98.729 782.13 c
h
99.038 782.157 m
99.055 781.967 99.034 781.784 98.975 781.606 c
98.917 781.429 98.831 781.271 98.716 781.133 c
98.601 780.995 98.46 780.881 98.292 780.791 c
98.123 780.702 97.943 780.648 97.75 780.632 c
97.555 780.615 97.372 780.635 97.198 780.692 c
97.025 780.748 96.863 780.838 96.714 780.961 c
96.573 781.078 96.457 781.217 96.37 781.379 c
96.283 781.542 96.23 781.719 96.213 781.912 c
96.19 782.168 96.233 782.408 96.341 782.632 c
96.449 782.856 96.606 783.039 96.812 783.18 c
97.02 783.328 97.251 783.412 97.502 783.434 c
97.753 783.455 97.995 783.413 98.225 783.306 c
98.455 783.199 98.643 783.046 98.787 782.846 c
98.931 782.647 99.015 782.416 99.038 782.157 c
f*
67.912 769.034 m
70.123 769.806 l
68.426 767.49 l
68.185 767.746 l
69.293 769.196 l
67.362 768.527 l
68.179 770.387 l
66.626 769.398 l
66.394 769.644 l
68.849 771.157 l
67.912 769.034 l
h
71.809 768.337 m
73.034 767.551 l
72.865 767.294 l
71.924 767.897 l
71.51 767.267 l
72.427 766.679 l
72.258 766.422 l
71.341 767.01 l
70.781 766.158 l
71.722 765.555 l
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70.328 766.083 l
71.809 768.337 l
h
74.637 766.729 m
75.173 766.547 l
75.35 766.486 75.514 766.409 75.664 766.314 c
75.819 766.209 75.947 766.088 76.047 765.95 c
76.153 765.802 76.222 765.633 76.256 765.443 c
76.272 765.349 76.274 765.249 76.263 765.145 c
76.252 765.041 76.227 764.932 76.187 764.819 c
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76.102 764.573 75.984 764.386 75.825 764.226 c
75.66 764.064 75.449 763.958 75.192 763.906 c
74.934 763.855 74.643 763.885 74.318 763.996 c
73.751 764.188 l
74.637 766.729 l
h
74.857 766.33 m
74.173 764.369 l
74.369 764.303 l
74.736 764.178 75.051 764.172 75.313 764.287 c
75.568 764.398 75.745 764.597 75.845 764.882 c
75.852 764.902 l
75.905 765.056 75.927 765.201 75.917 765.338 c
75.907 765.475 75.865 765.605 75.791 765.727 c
75.646 765.967 75.388 766.149 75.017 766.276 c
74.857 766.33 l
h
78.891 764.126 m
78.224 765.75 l
78.612 765.697 l
79.111 764.469 l
79.938 765.513 l
80.319 765.459 l
79.226 764.079 l
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78.727 762.967 l
78.891 764.126 l
h
84.123 763.667 m
84.178 763.276 l
83.974 763.12 83.749 763.024 83.503 762.99 c
83.248 762.955 83.001 762.985 82.764 763.082 c
82.526 763.179 82.326 763.332 82.163 763.539 c
82.018 763.721 81.931 763.923 81.899 764.144 c
81.894 764.182 81.89 764.207 81.889 764.218 c
81.867 764.369 81.871 764.516 81.901 764.658 c
81.928 764.789 81.978 764.916 82.048 765.038 c
82.182 765.265 82.347 765.437 82.543 765.553 c
82.739 765.669 82.929 765.74 83.115 765.766 c
83.374 765.802 83.614 765.777 83.835 765.69 c
83.89 765.303 l
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83.039 765.453 82.95 765.428 82.866 765.392 c
82.783 765.356 82.705 765.307 82.63 765.245 c
82.485 765.127 82.375 764.976 82.3 764.794 c
82.225 764.612 82.2 764.435 82.224 764.264 c
82.254 764.05 82.331 763.865 82.452 763.709 c
82.569 763.557 82.716 763.443 82.893 763.368 c
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83.71 763.33 83.927 763.453 84.123 763.667 c
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86.782 766.387 m
85.685 765.948 l
85.569 766.233 l
87.18 766.876 l
86.803 764.158 l
88.083 764.669 l
88.199 764.385 l
86.41 763.67 l
86.782 766.387 l
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88.638 767.675 m
91.554 767.141 l
90.369 768.753 l
90.649 768.954 l
92.314 766.69 l
89.394 767.212 l
90.587 765.588 l
90.315 765.393 l
88.638 767.675 l
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92.051 770.215 m
92.989 771.32 l
93.227 771.123 l
92.506 770.274 l
93.088 769.791 l
93.791 770.619 l
94.028 770.422 l
93.326 769.594 l
94.114 768.941 l
94.834 769.79 l
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94.134 768.488 l
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BT
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(Robert M. Proczka)Tj
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(The formation of new vessels is a complex problem. In this process the key role is played by the vascular-)Tj
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(receptory dla naczyniowo-rdbonkowego czynnika wzrostu, VEGF)Tj
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(www.angiologia.pl)Tj
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(high prevalence of )Tj
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(arterial hypertension, and the)Tj
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[(addiction to )]TJ
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[(development. In case of full patients compliance and)]TJ
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-0.0003 Tc
-0.0644 Tw
(przyjto wskanik kostkowo-ramienny poniej 0,9\) [1].)Tj
0 -1.4467 TD
0.0653 Tw
(W Polsce okoo 30 000 rocznie pacjentw zgasza si)Tj
0 -1.4433 TD
-0.0008 Tc
0.0556 Tw
(po raz pierwszy do lekarza z objawami niedokrwienia)Tj
T*
0.0001 Tc
-0.0528 Tw
(koczyn dolnych, a spord nich u okoo 10% koniecz-)Tj
0 -1.4467 TD
-0.0003 Tc
0.0013 Tw
(na jest amputacja koczyny [2].)Tj
1.5733 -1.4433 TD
-0.0101 Tc
0.0722 Tw
(Leczenie choroby niedokrwiennej koczyn dolnych)Tj
-1.5733 -1.4433 TD
-0.0106 Tc
-0.0028 Tw
(jest bardzo trudne. W przypadku pojedynczych zwe)Tj
0 -1.4467 TD
-0.0102 Tc
-0.0305 Tw
(naczy dobre wyniki przynosi leczenie chirurgiczne \(po-)Tj
0 -1.4433 TD
-0.0218 Tc
-0.0694 Tw
(mostowanie lub udranianie naczy\). Ostatnio istotn rol)Tj
T*
-0.0107 Tc
0.0811 Tw
(zaczy odgrywa metody przezskrnej plastyki naczy-)Tj
0 -1.4467 TD
-0.0102 Tc
0.0022 Tw
(niowej. Gdy zmiany s rozsiane lub co gorsze do-)Tj
0 -1.4433 TD
-0.0105 Tc
0.0037 Tw
(tycz take maych naczy, leczenie chirurgiczne czsto)Tj
T*
-0.0044 Tw
(jest niemoliwe. Prby leczenia farmakologicznego pre-)Tj
0 -1.4467 TD
-0.0107 Tc
0.0685 Tw
(paratami naczyniorozszerzajcymi lub/i poprawiajcymi)Tj
0 -1.4433 TD
-0.0103 Tc
0.0037 Tw
(plastyczno ciany krwinek niestety nie przynosz spo-)Tj
T*
-0.0106 Tc
-0.0232 Tw
(dziewanych efektw u pacjentw z zaawansowan cho-)Tj
0 -1.4467 TD
-0.0104 Tc
0 Tw
(rob niedokrwienn serca. Rwnie dottnicze lub pre-)Tj
0 -1.4433 TD
-0.0102 Tc
0.0138 Tw
(ferowane przez innych autorw doylne wlewy prosta-)Tj
T*
-0.0105 Tc
-0.0532 Tw
(glandyn PGE1 \(preparaty stosowane w Polsce to Prosta-)Tj
0 -1.4467 TD
0.1194 Tw
(vasin i Iloprost\) okazay si niewystraczajce. Leczenie)Tj
0 -1.4433 TD
-0.0155 Tw
(zachowawcze spowalnia jednak postp choroby, umo-)Tj
T*
-0.0556 Tw
(liwiajc wytworzenie krenia obocznego. W przypadku)Tj
0 -1.4467 TD
-0.065 Tw
(penej wsppracy z pacjentem, jeli podejmuje on syste-)Tj
0 -1.4433 TD
-0.0269 Tw
(matyczny wysiek fizyczny, wykazano, e dziki rehabili-)Tj
T*
-0.0101 Tc
-0.0023 Tw
(tacji dystans chromania wyduy si o 122% [1].)Tj
1.5733 -1.4467 TD
-0.0061 Tc
-0.0689 Tw
(Mechanizm powstawania nowych naczy jest zagad-)Tj
-1.5733 -1.4433 TD
0.0118 Tc
0.1389 Tw
(nieniem zoonym, w ktrym prawdopodobnie klu-)Tj
T*
0.0097 Tc
(czow rol peni naczyniowo-rdbonkowy )Tj
20.84 0 TD
-0.0099 Tc
0 Tw
(czynnik)Tj
-20.84 -1.4467 TD
-0.0201 Tc
0.0479 Tw
(wzrostu \(VEGF,)Tj
/F5 1 Tf
6.8733 0 TD
-0.0185 Tc
0.0457 Tw
[( vascular endothelial growth factor)]TJ
/F2 1 Tf
13.9933 0 TD
-0.015 Tc
0.0472 Tw
(\) [3, 4].)Tj
-20.8667 -1.4433 TD
0 Tc
-0.025 Tw
[(N)21(a)10(ley on do grupy angiogennych czynnikw wzrosto-)]TJ
T*
-0.0016 Tc
-0.0691 Tw
(wych i jest specyficznym mitogenem dla komrek rd-)Tj
0 -1.4467 TD
-0.0019 Tc
-0.0694 Tw
(bonka. Jest wydzielany przez makrofagi, komrki rd-)Tj
0 -1.4433 TD
-0.0004 Tc
-0.0611 Tw
(bonka naczyniowego, komrki mini gadkich naczy,)Tj
T*
-0.0001 Tc
-0.0629 Tw
(fibroblasty oraz komrki nowotworowe [5, 6]. Wartio-)Tj
0 -1.4467 TD
-0.0031 Tc
-0.0691 Tw
(vaara i wsp. [7] odnotowali wzmoon produkcj VEGF)Tj
0 -1.4433 TD
-0.0001 Tc
0.0833 Tw
(w miej)Tj
3.0567 0 TD
0.0144 Tc
0.0856 Tw
(scu aktywacji pytek oraz moliwo magazy-)Tj
-3.0567 -1.4433 TD
0.0074 Tc
-0.0664 Tw
(nowania i )Tj
4.3998 0 TD
-0.0081 Tc
-0.0691 Tw
(uwalniania VEGF przez pytki krwi [8]. Zwik-)Tj
-4.3998 -1.4467 TD
0.0133 Tc
0.2 Tw
(szanie przepuszczalnoci naczy indukowane przez)Tj
0 -1.4433 TD
-0.002 Tc
0 Tw
[(VEGF )]TJ
2.9197 0 TD
-0.0152 Tc
0.0846 Tw
(\(ok. 50 000 razy wiksze w porwnaniu z hista-)Tj
-2.9197 -1.4433 TD
-0.0154 Tc
-0.0472 Tw
(min\) sprawio, e pocztkowo nazywano go czynnikiem)Tj
0 -1.4467 TD
-0.0158 Tc
-0.0037 Tw
(przepuszczalnoci naczy \(VPF, )Tj
/F5 1 Tf
13.7467 0 TD
-0.0162 Tc
-0.0056 Tw
(vascular permeability fac-)Tj
-13.7467 -1.4433 TD
0 Tw
(tor)Tj
/F2 1 Tf
1.1567 0 TD
-0.0184 Tc
-0.0689 Tw
(\) [9]. Naczyniowo-rdbonkowy czynnik wzrostu wy-)Tj
-1.1567 -1.4433 TD
-0.0174 Tc
-0.0691 Tw
(wouje rwnie uwalnianie czynnika von Willebranda i ak-)Tj
0 -1.4467 TD
-0.0153 Tc
0.0578 Tw
(tywatora plazminogenu typu tkankowego oraz urokina-)Tj
0 -1.4433 TD
-0.027 Tc
-0.069 Tw
[(zowego, a take dziaa chemotaktyczni)-15(e)0( na makrofagi [10].)]TJ
1.89 -1.4433 TD
-0.0007 Tc
-0.0127 Tw
(Informacja genetyczna dla VEGF w postaci 8 ekso-)Tj
-1.89 -1.4467 TD
-0.0003 Tc
0.0852 Tw
(nw zlokalizowana jest na ramieniu krtkim chromo-)Tj
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BT
/F2 1 Tf
10 0 0 10 501.99 40.175 Tm
0 g
/GS2 gs
0.0045 Tc
0 Tw
(145)Tj
ET
0 G
0 J 0 j 0.24 w 10 M []0 d
1 i
62.34 768.395 m
518.76 768.395 l
S
BT
/F3 1 Tf
8 0 0 8 336.66 772.535 Tm
-0.0014 Tc
0.0062 Tw
(The role of VEGF in angiogenesis, )Tj
/F2 1 Tf
16.7663 0 TD
-0.0016 Tc
(Proczka et al.)Tj
-26.6925 -91.3463 TD
0.0094 Tc
0 Tw
(www.angiologia.pl)Tj
9 0 0 9 62.34 734.015 Tm
-0.0001 Tc
0.1139 Tw
[(this regulatory protein formed. They consist of 121,)]TJ
0 -1.4433 TD
0.0001 Tc
0.0047 Tw
(165, 189, 206 amino acids. The biologic importance of)Tj
T*
-0.0004 Tc
0.0629 Tw
(expression most isoforms hasnt been discovered yet.)Tj
0 -1.4467 TD
-0.0161 Tc
-0.0695 Tw
(It is assumed that VEGF 165 is the most common product)Tj
0 -1.4433 TD
-0.0104 Tc
0.113 Tw
(of the VEGF gene and has the highest biologic activity)Tj
T*
0.0039 Tc
0.1415 Tw
[([11]. VEGF 121 )]TJ
7.6452 0 TD
0.0132 Tc
0.1416 Tw
(and VEGF 165 are mainly secreted)Tj
-7.6452 -1.4467 TD
0.0137 Tc
0.4833 Tw
(outside the cells, where they are found in an)Tj
0 -1.4433 TD
0.1786 Tw
(unconjugated form. The isoforms 189 and 206 are)Tj
T*
-0.0003 Tc
-0.0321 Tw
[(combined with heparan sulfate inside the cell. They do)]TJ
0 -1.4467 TD
-0.0001 Tc
0.073 Tw
(not probably play any role in neoangiogenesis [5, 12].)Tj
0 -1.4433 TD
-0.0003 Tc
0.0493 Tw
(The authors underline, though, that all forms are very)Tj
T*
-0.0005 Tc
0.0461 Tw
(active in the process of increasing vessel permeability.)Tj
0 -1.4467 TD
-0.0103 Tc
0.0315 Tw
(An additional form VEGF 145 has been identified in the)Tj
0 -1.4433 TD
0.0038 Tc
0.2583 Tw
(human endometrium. The biologic )Tj
16.78 0 TD
0.0147 Tc
0.2611 Tw
(function of this)Tj
-16.78 -1.4433 TD
-0.0022 Tc
-0.0695 Tw
(substance has not been identified yet. All these isoforms)Tj
0 -1.4467 TD
0 Tc
0.1389 Tw
(are the product of the VEGF-A gene. The additional)Tj
0 -1.4433 TD
-0.0004 Tc
-0.0545 Tw
[(types are: VEGF-B, C, D, E. Isoform C is also important)]TJ
T*
-0.0002 Tc
0.1229 Tw
(in the angiogenesis. It is responsible for regulation of)Tj
0 -1.4467 TD
-0.0015 Tc
0 Tw
(limfangiogenesis.)Tj
1.5733 -1.4433 TD
-0.0004 Tc
0.1124 Tw
(Hypoxia is a mandatory signal for the start of the)Tj
-1.5733 -1.4433 TD
0.0006 Tc
0.1389 Tw
(angiogenesis process and the expression of the gene)Tj
0 -1.4467 TD
-0.0004 Tc
-0.0063 Tw
[(which codes VEGF. This brings about the transcription)]TJ
0 -1.4433 TD
-0.0007 Tc
-0.0694 Tw
(of special substances known as the hypoxia induced fac-)Tj
T*
-0.0259 Tw
(tors such as HIF-1)Tj
/F6 1 Tf
7.9567 0 TD
0 Tc
0 Tw
(a)Tj
/F2 1 Tf
0.5933 0 TD
-0.0006 Tc
-0.0278 Tw
(, HIF-1)Tj
/F6 1 Tf
3.0833 0 TD
0 Tc
0 Tw
(b)Tj
/F2 1 Tf
0.5167 0 TD
-0.0009 Tc
-0.0278 Tw
(, HIF 2)Tj
/F6 1 Tf
2.9633 0 TD
0 Tc
0 Tw
(a)Tj
/F2 1 Tf
0.5933 0 TD
0.0002 Tc
-0.0278 Tw
[( [14, 15]. Activated)]TJ
-15.7067 -1.4467 TD
-0.0001 Tc
-0.0327 Tw
(through hypoxia HIF proteins move to the cell nucleus,)Tj
0 -1.4433 TD
-0.0003 Tc
0.066 Tw
(where they take part in formation of regulatory com-)Tj
T*
0.0018 Tc
0.1389 Tw
(plexes of the expression of VEGF. These complexes)Tj
0 -1.4467 TD
0.0134 Tc
0.1771 Tw
(consist of the HIF and the HRE \(hypoxia response)Tj
0 -1.4433 TD
-0.0002 Tc
0.0833 Tw
(element located on the 5 region of the VEGF coding)Tj
T*
-0.0074 Tc
-0.069 Tw
[(gene\). Through the HIF activation hypoxia also increases)]TJ
0 -1.4467 TD
-0.0003 Tc
-0.0049 Tw
(the stability of the VEGF mRNA through an increase in)Tj
0 -1.4433 TD
0.0401 Tw
(its halftime [16]. It is highly probable that hypoxia also)Tj
T*
0.0001 Tc
0.0263 Tw
(leads to production of VEGF not only directly through)Tj
0 -1.4467 TD
0.0138 Tc
0.1764 Tw
(activation of the VEGF gene, but also inducing the)Tj
0 -1.4433 TD
-0.0039 Tc
-0.069 Tw
(transcription of gene which codes COX-2 and increases)Tj
T*
0.0138 Tc
0.237 Tw
(the concentration of prostoglandins. This in effect)Tj
0 -1.4467 TD
0.0012 Tc
0.1389 Tw
(increases the expression of VEGF in fibroblasts [17].)Tj
0 -1.4433 TD
-0.0004 Tc
0.0094 Tw
(Kappel et al [18] has proven the positive effect of HIF-)Tj
T*
0 Tc
0 Tw
(2)Tj
/F6 1 Tf
0.5633 0 TD
(a)Tj
/F2 1 Tf
0.6033 0 TD
0.0108 Tc
0.1389 Tw
[( on the transcription of VEGFR-2 \(explanation of)]TJ
-1.1667 -1.4467 TD
-0.0001 Tc
-0.0161 Tw
(importance of this fact further in the text\) Vincent et al)Tj
0 -1.4433 TD
0.0001 Tc
0.1266 Tw
([19] noticed the influence of this protein also on the)Tj
T*
-0.0002 Tc
0.0028 Tw
(IGF-2 and erythropoetin.)Tj
1.5733 -1.4467 TD
-0.0041 Tc
-0.0694 Tw
(Hypoxia is also responsible for the synthesis of other)Tj
-1.5733 -1.4433 TD
0.0095 Tc
0.0587 Tw
(growth factors such as basic fibroblast growth factor)Tj
T*
0.1222 Tw
(\(bFGF\), platelet derived growth factor \(PDGF\), pla-)Tj
0 -1.4467 TD
0.0062 Tc
-0.0694 Tw
[(centa growth factor \(PlGF\). It also indirectly causes the)]TJ
0 -1.4433 TD
0.0098 Tc
0.0299 Tw
(synthesis of Nitric oxide \(NO\) [20, 21]. The increase)Tj
T*
0.0095 Tc
0.1069 Tw
(in expression of the VEGF caused by these cytokins)Tj
0 -1.4467 TD
0.0097 Tc
-0.0247 Tw
[(underlines the key role of vascular endothelial growth)]TJ
0 -1.4433 TD
0.001 Tw
(factor in the process of vessel formation.)Tj
1.5733 -1.4433 TD
0.01 Tc
-0.0019 Tw
(Endothelial cells are the main, but not the only ef-)Tj
-1.5733 -1.4467 TD
0.0093 Tc
-0.0408 Tw
(fector cells for VEGF. They have three kinds of recep-)Tj
26.6167 73.6667 TD
-0.0117 Tc
-0.0695 Tw
(somu 6. Pierwszy ekson genu dla VEGF zawiera sekwen-)Tj
0 -1.4433 TD
-0.0008 Tc
-0.0315 Tw
(cj sekrecyjn pozwalajc na naturalne wydzielanie tej)Tj
T*
-0.0005 Tc
-0.0566 Tw
(cytokiny. Na drodze alternatywnego skadania \()Tj
/F5 1 Tf
20.75 0 TD
-0.0014 Tc
0 Tw
(alterna-)Tj
-20.75 -1.4467 TD
-0.0016 Tc
0.05 Tw
(tive splicing)Tj
/F2 1 Tf
4.8967 0 TD
-0.0006 Tc
0.0537 Tw
(\) mRNA powstaj cztery formy tego biaka)Tj
-4.8967 -1.4433 TD
-0.0002 Tc
0.0468 Tw
(regulatorowego. Zbudowane s one ze 121, 165, 189)Tj
T*
-0.0001 Tc
-0.0473 Tw
(lub z 206 aminokwasw. )Tj
11.0633 0 TD
-0.0101 Tc
-0.0482 Tw
(Dotychczas cakowicie nie po-)Tj
-11.0633 -1.4467 TD
-0.0153 Tc
-0.0689 Tw
(znano biologicznego znaczenia ekspresji rnych izoform)Tj
0 -1.4433 TD
-0.0107 Tc
0.0278 Tw
(VEGF. Uwaa si, e produkt genu VEGF )Tj
19.7967 0 TD
0.009 Tc
0 Tw
(VEGF165)Tj
-19.7967 -1.4433 TD
-0.0009 Tc
-0.0689 Tw
[(wystpuje najpowszechniej i posiada najwiksz aktyw-)]TJ
0 -1.4467 TD
0.0098 Tc
0.063 Tw
(no biologiczn [11]. Czynniki VEGF121 i VEGF165)Tj
0 -1.4433 TD
-0.0008 Tc
-0.046 Tw
[(w)-12.1( wikszoci wydzielane s poza obrb komrki, gdzie)]TJ
T*
-0.0005 Tc
0.0911 Tw
(pozostaj w postaci niezwizanej, natomiast izoformy)Tj
0 -1.4467 TD
0.0096 Tc
-0.0294 Tw
(189 i 206 w przestrzeni komrkowej ulegaj wizaniu)Tj
0 -1.4433 TD
-0.0006 Tc
-0.0629 Tw
[(z)-12.3( siarczanem heparanu i najprawdopodobniej nie peni)]TJ
T*
-0.0003 Tc
0.1133 Tw
(najwaniejszej roli w neoangiogenezie )Tj
17.4649 0 TD
([5, 12].)Tj
3.2984 0 TD
0.0086 Tc
0.1167 Tw
[( Jedno-)]TJ
-20.7633 -1.4467 TD
0.0074 Tc
0.0703 Tw
(czenie autorzy podkrelaj, e wszystkie cztery izo-)Tj
0 -1.4433 TD
-0.0066 Tc
-0.0694 Tw
(formy charakteryzuj si wysok )Tj
14.2326 0 TD
(aktywnoci jako )Tj
7.5475 0 TD
-0.0148 Tc
(czyn-)Tj
-21.78 -1.4433 TD
0.0071 Tc
0.1389 Tw
(niki przepuszczalnoci n)Tj
11.05 0 TD
0.012 Tc
0 Tw
[(aczy. )]TJ
3.2526 0 TD
0.0067 Tc
(Dodatkow )Tj
5.7054 0 TD
0.0121 Tc
(izoform)Tj
-20.008 -1.4467 TD
-0.0047 Tc
-0.0689 Tw
[()-12.4( VEGF145 zidentyfikowano w endometrium ludzkim,)]TJ
0 -1.4433 TD
-0.009 Tc
-0.069 Tw
(jednak jeszcze dokadnie nie ustalono jej aktywnoci bio-)Tj
T*
-0.0006 Tc
0.0534 Tw
(logicznej. Wszystkie powysze izoformy s kodowane)Tj
0 -1.4467 TD
0.0262 Tw
(przez gen VEGF-A. Naley wspomnie take o dodat-)Tj
0 -1.4433 TD
-0.0004 Tc
-0.0655 Tw
(kowych rodzajach VEGF; B, C, D, E. Z punktu widzenia)Tj
T*
-0.0006 Tc
0.1222 Tw
(angiogenezy wana jest izoforma C, ktra jest odpo-)Tj
0 -1.4467 TD
0 Tw
(wiedzialna za regulacj procesw limfangiogenezy.)Tj
1.89 -1.4433 TD
0.1097 Tw
(Niezbdnym sygnaem do rozpoczcia procesw)Tj
-1.89 -1.4433 TD
-0.0444 Tw
(angiogenezy, a tym samym do ekspresji genu kodujce-)Tj
0 -1.4467 TD
-0.0029 Tc
-0.0694 Tw
(go VEGF jest niedotlenienie tkanek [13]. Pod jego wpy-)Tj
0 -1.4433 TD
-0.0003 Tc
-0.0689 Tw
(wem dochodzi do wytworzenia transkrypcyjnych czyn-)Tj
T*
-0.0006 Tc
-0.0602 Tw
(nikw indukowanych przez hipoksj, takich jak HIF-1)Tj
/F6 1 Tf
23.2233 0 TD
0 Tc
0 Tw
(a)Tj
/F2 1 Tf
0.5933 0 TD
(,)Tj
-23.8167 -1.4467 TD
0.0081 Tc
(HIF-1)Tj
/F6 1 Tf
2.6067 0 TD
0 Tc
(b)Tj
/F2 1 Tf
0.5167 0 TD
0.0097 Tc
0.1 Tw
(, HIF-2)Tj
/F6 1 Tf
3.2833 0 TD
0 Tc
0 Tw
(a)Tj
/F2 1 Tf
0.6067 0 TD
0.117 Tc
( \()Tj
/F5 1 Tf
0.75 0 TD
0.0086 Tc
0.1028 Tw
(hipoxia-inducible transcription factor)Tj
/F2 1 Tf
15.9867 0 TD
0 Tc
0 Tw
(\))Tj
-23.75 -1.4433 TD
0.0143 Tc
0.139 Tw
[([14, 15]. )]TJ
4.4263 0 TD
0.0037 Tc
0.1389 Tw
(Uaktywnione w wyniku hipoksji biaka HIF)Tj
-4.4263 -1.4433 TD
-0.0128 Tc
-0.0694 Tw
(przemieszczaj si do jdra komrkowego, gdzie uczest-)Tj
0 -1.4467 TD
-0.0006 Tc
-0.0356 Tw
(nicz w tworzeniu kompleksw regulujcych ekspresj)Tj
0 -1.4433 TD
-0.0667 Tw
(genw VEGF. )Tj
6.2567 0 TD
-0.0103 Tc
-0.0676 Tw
(Kompleksy te to poczony HIF z elemen-)Tj
-6.2567 -1.4433 TD
-0.0106 Tc
0.0611 Tw
(tem odpowiedzi na hipoksj HRE \()Tj
/F5 1 Tf
15.35 0 TD
-0.0102 Tc
(hipoxia response ele-)Tj
-15.35 -1.4467 TD
-0.0081 Tc
0 Tw
(ment)Tj
/F2 1 Tf
2.1633 0 TD
-0.0065 Tc
0.1389 Tw
(\) znajdujcym si w regionie 5 genu kodujcego)Tj
-2.1633 -1.4433 TD
-0.011 Tc
0.0879 Tw
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[(depends)-7.2( on competitive bonding in the active places of)]TJ
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[(that the stimulation of VEGFR-2 is necessary for the)]TJ
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[(start of the response from the endothelial cells. I)16.7(s)]TJ
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[(i)16.6(nteresting that the blockage of VEGFR-1 does not)]TJ
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[(of the tubes made up from proliferating endothelial)]TJ
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-0.018 Tw
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[(the first type. Synthesis of n)-14.2(itric oxide synthase-2 \(NOS-)]TJ
T*
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[(-)-14.7(2\), stimulated by VEGF, and the release of NO is inhibi-)]TJ
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(ted by the blockage of VEGFR-1. In turn VEGFR-1,)Tj
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[([25],)-2.9( )]TJ
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[(nastpuje )]TJ
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(to the area of ischemia and the other way from the)Tj
0 -1.4433 TD
-0.0007 Tc
0.0423 Tw
(area of ischemia to properly perfused tissues. EPCs at)Tj
T*
-0.0154 Tc
-0.0694 Tw
[(t)-18.1(he site of ischemia differentiate into endothelial cells, and)]TJ
0 -1.4467 TD
-0.0102 Tc
0.1014 Tw
[(later quickly proliferate. This function can be debilita-)]TJ
0 -1.4433 TD
-0.005 Tc
-0.0693 Tw
[(ted)5( by hiperglicemia, hipercholesterolemia, hiperhomo-)]TJ
T*
-0.0003 Tc
-0.0361 Tw
[(cysteinemia, and the ageing of the organism [31, 32]. It)]TJ
0 -1.4467 TD
-0.0007 Tc
0.0439 Tw
(has also been proven that VEGF has a direct effect on)Tj
0 -1.4433 TD
-0.0002 Tc
-0.0022 Tw
(proliferating activity of the EPCs [30].)Tj
1.5733 -1.4433 TD
0.0015 Tc
-0.0688 Tw
(More knowledge about vascular endothelial growth)Tj
-1.5733 -1.4467 TD
0.005 Tc
0.0148 Tw
(factor allows to use this cytokin in clinical trials. Some)Tj
0 -1.4433 TD
-0.0175 Tw
(authors through blockage try to inhibit proliferation of)Tj
T*
0.0046 Tc
0.0278 Tw
(neoplastic cells, others want to treat ischemic disease)Tj
0 -1.4467 TD
-0.006 Tc
-0.0691 Tw
(of the heart and the lower limbs. In 1994 the Isner group)Tj
0 -1.4433 TD
0.0117 Tc
0.1389 Tw
(proposed the use of VEGF in therapy of peripheral)Tj
T*
0.0048 Tc
0.1041 Tw
(ischemic disease. Unfortunately direct administration)Tj
0 -1.4467 TD
-0.0695 Tw
(of the protein was complicated by necessity of multiple)Tj
0 -1.4433 TD
0.0986 Tw
(injections, as well as difficulty in synthesis and stand-)Tj
T*
0.0047 Tc
0.1014 Tw
(ardization. Gene therapy, which in this case is direct)Tj
0 -1.4467 TD
0.0005 Tc
-0.069 Tw
(administration of plasmid DNA into the muscles, seems)Tj
0 -1.4433 TD
0.0045 Tc
0.0883 Tw
(to be a better strategy. The pioneers of this method)Tj
T*
0.0043 Tc
0.1216 Tw
[(are the Isner group \(Harvard, Boston, USA\) and the)]TJ
0 -1.4467 TD
-0.0007 Tc
-0.0689 Tw
(scientists from Karolinska Institute \(Sweden\). Intramus-)Tj
0 -1.4433 TD
0.0141 Tc
0.1389 Tw
(cular injection of the naked plasmid causes striated)Tj
T*
0.0046 Tc
0.0255 Tw
(muscle cells to express a foreign gene, in this case for)Tj
0 -1.4467 TD
0.0183 Tc
0.181 Tw
(VEGF. It can be noticed that despite intermediate)Tj
0 -1.4433 TD
-0.0003 Tc
-0.0694 Tw
(increase in VEGF levels in the whole circulatory system,)Tj
T*
0.0048 Tc
0.0321 Tw
(the development of vessels occurs only at the sites of)Tj
0 -1.4467 TD
0.0041 Tc
0 Tw
(ischemia.)Tj
28.19 73.6667 TD
-0.0187 Tc
-0.0694 Tw
(Zwizkiem poredniczcym w odpowiedzi komrko-)Tj
-1.5733 -1.4433 TD
-0.0156 Tc
0.0063 Tw
(wej na aktywacj receptorw typu pierwszego jest NO.)Tj
T*
-0.0006 Tc
0.0633 Tw
[(S)16.4(tymulowana przez VEGF syntaza NOS-2 \()]TJ
/F5 1 Tf
19.3967 0 TD
-0.0013 Tc
0.0666 Tw
(nitric oxide)Tj
-19.3967 -1.4467 TD
-0.0092 Tc
0 Tw
(synthase-2)Tj
/F2 1 Tf
4.4833 0 TD
-0.0088 Tc
-0.0694 Tw
(\) i uwalnianie NO s hamowane blokowaniem)Tj
-4.4833 -1.4433 TD
-0.0005 Tc
0.1157 Tw
(VEGFR-1. Z kolei VEGFR-1 poprzez NO negatywnie)Tj
T*
-0.0134 Tc
-0.0694 Tw
(reguluje proliferacj komrek rdbonka wytwarzanych)Tj
0 -1.4467 TD
-0.0058 Tc
-0.0689 Tw
(za porednictwem aktywacji VEGFR-2, ale jednoczenie)Tj
0 -1.4433 TD
-0.0007 Tc
0.07 Tw
(odpowiadaj za uporzdkowane ustawienie. Rol NO)Tj
T*
-0.0001 Tc
-0.018 Tw
(udowodniono rwnie w reendotelializacji zniszczonej)Tj
0 -1.4467 TD
-0.0002 Tc
-0.05 Tw
(ttnicy [26]. Substratem dla produkcji NO jest L-argini-)Tj
0 -1.4433 TD
-0.0003 Tc
0.0908 Tw
(na, z ktrej pod wpywem syntazy NO)Tj
5 0 0 5 461.4 602.675 Tm
0 Tc
0 Tw
(2)Tj
9 0 0 9 464.16 604.025 Tm
-0.0004 Tc
0.0917 Tw
[( powstaje cy-)]TJ
-18.03 -1.4433 TD
0.0005 Tc
0.0833 Tw
(trulina i NO. )Tj
6.1333 0 TD
-0.0108 Tc
[(Schwarzacher i wsp. [2)-10.8(7)-10.8(])]TJ
/F3 1 Tf
11.15 0 TD
0 Tc
0 Tw
( )Tj
/F2 1 Tf
0.38 0 TD
-0.0105 Tc
0.0889 Tw
(spostrzegli ko-)Tj
-17.6633 -1.4467 TD
-0.006 Tc
0.1389 Tw
(rzystny wpyw suplementacji L-argininy na gojenie si)Tj
0 -1.4433 TD
0.0036 Tc
0.3541 Tw
(uszkodzonego rdbonka, co mona wytumaczy)Tj
T*
-0.011 Tc
-0.0444 Tw
(zwikszon produkcj VEGF spowodowan zwikszon)Tj
0 -1.4467 TD
-0.0106 Tc
0.0695 Tw
(syntez NO. Oprcz stenia L-argininy synteza VEGF)Tj
0 -1.4433 TD
-0.0104 Tc
-0.0493 Tw
(zaley take od stenia lipidw, a dokadniej LDL. Utle-)Tj
T*
0.0805 Tw
(nowany LDL poprzez blokowanie syntezy NO hamuje)Tj
0 -1.4467 TD
-0.0108 Tc
0.0019 Tw
[(migracj komrek rdbonka [28)-12.5(])0.2(.)]TJ
1.89 -1.4433 TD
0.0132 Tc
0.1544 Tw
(Jak wspomniano, receptory dla VEGF posiadaj)Tj
-1.89 -1.4433 TD
-0.0007 Tc
-0.012 Tw
(przede wszystkim komrki rdbonka. Inn grup ko-)Tj
0 -1.4467 TD
-0.001 Tc
0.0453 Tw
(mrek wan ze wzgldu na angiogenez, posiadajc)Tj
0 -1.4433 TD
-0.0097 Tc
-0.0694 Tw
(na swojej powierzchni VEGFR-2, s endotelialne komr-)Tj
T*
-0.0027 Tc
-0.0686 Tw
(ki progenitorowe \(EPCs, )Tj
/F5 1 Tf
10.99 0 TD
-0.0032 Tc
-0.0667 Tw
(endothelial progenitor cells)Tj
/F2 1 Tf
11.0833 0 TD
-0.0036 Tc
-0.0722 Tw
(\). Te)Tj
-22.0733 -1.4467 TD
-0.0062 Tc
-0.0694 Tw
(wywodzce si ze szpiku kostnego komrki przedostaj)Tj
0 -1.4433 TD
-0.0006 Tc
-0.0016 Tw
(si do krenia, a nastpnie poprzez ukad krwionony)Tj
T*
-0.0004 Tc
0.1072 Tw
( do ognisk niedokrwienia [29]. Odkrycie EPCs po-)Tj
0 -1.4467 TD
-0.0025 Tc
-0.0695 Tw
(zwolio udowodni, e procesy angiogenezy s ukierun-)Tj
0 -1.4433 TD
-0.0002 Tc
0.0555 Tw
(kowane nie tylko na ognisko niedokrwienne, ale rw-)Tj
T*
0.1268 Tw
(nie od strony niedokrwienia do zdrowego naczynia.)Tj
0 -1.4467 TD
-0.0334 Tc
-0.0681 Tw
(Endotelialne komrki progenitorowe, przebywajc w )Tj
21.9158 0 TD
-0.0123 Tc
0 Tw
(ogni-)Tj
-21.9158 -1.4433 TD
-0.0003 Tc
0.0768 Tw
(sku niedokrwiennym, rnicuj si do komrek rd-)Tj
T*
-0.0033 Tc
-0.0691 Tw
(bonka, a nastpnie ulegaj szybkiej proliferacji. Ta funk-)Tj
0 -1.4467 TD
-0.0006 Tc
-0.0468 Tw
(cja moe jednak ulec upoledzeniu w warunkach hiper-)Tj
0 -1.4433 TD
0.0083 Tc
0.1389 Tw
(glikemii, hipercholesterolemii, hiperhomocysteinemii)Tj
T*
-0.0005 Tc
-0.0521 Tw
(oraz wraz ze starzeniem si organizmu [31, 32]. Iwagu-)Tj
0 -1.4467 TD
0.001 Tc
0.1389 Tw
(ro i wsp. [30] udowodnili, e VEGF ma bezporedni)Tj
0 -1.4433 TD
-0.0005 Tc
-0.0014 Tw
(wpyw na aktywno proliferacyjn EPCs.)Tj
1.89 -1.4433 TD
0.0042 Tc
0.1389 Tw
(Dziki coraz wikszej wiedzy, moliwe stao si)Tj
-1.89 -1.4467 TD
0.011 Tc
(przeprowadzenie prby wykorzystania naczyniowo-)Tj
0 -1.4433 TD
-0.0003 Tc
0.0367 Tw
(rdbonkowego czynnika wzrostu do celw terapeu-)Tj
T*
-0.0014 Tc
-0.0694 Tw
(tycznych. Niektrzy autorzy poprzez jego blokad pr-)Tj
0 -1.4467 TD
-0.0007 Tc
0.0155 Tw
(buj doprowadza do zahamowania proliferacji kom-)Tj
0 -1.4433 TD
-0.0037 Tc
-0.0685 Tw
(rek nowotworowych, inni chc leczy )Tj
16.5833 0 TD
-0.0014 Tc
-0.069 Tw
[(za pomoc VEGF)]TJ
-16.5833 -1.4433 TD
0.0097 Tc
0.0477 Tw
(choroby niedokrwienne serca oraz koczyn dolnych.)Tj
0 -1.4467 TD
-0.0003 Tc
0.0621 Tw
[(W)-10.6( 1994 roku Isner [33] zaproponowa wykorzystanie)]TJ
0 -1.4433 TD
-0.0005 Tc
0.0189 Tw
(VEGF w leczeniu niedokrwienia obwodowego. Jednak)Tj
T*
-0.0006 Tc
-0.0454 Tw
(bezporednie podawanie biaka czyo si z wielokrot-)Tj
0 -1.4467 TD
-0.0001 Tc
0.0479 Tw
(nymi iniekcjami oraz z trudnociami w syntezie i stan-)Tj
0 -1.4433 TD
-0.0031 Tc
-0.0694 Tw
(daryzacji. Lepsz strategi angiogennej terapi wydaje si)Tj
T*
-0.0006 Tc
0.0789 Tw
(terapia genowa, czyli podawanie plazmidowego DNA)Tj
0 -1.4467 TD
-0.0146 Tc
-0.069 Tw
(bezporednio do mini. Pionierem tej metody jest grupa)Tj
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/F2 1 Tf
10 0 0 10 62.34 40.175 Tm
0 g
/GS2 gs
0.0045 Tc
0 Tw
(148)Tj
ET
0 G
0 J 0 j 0.24 w 10 M []0 d
1 i
62.34 768.395 m
518.76 768.395 l
S
BT
8 0 0 8 62.34 772.535 Tm
-0.001 Tc
0.0021 Tw
(Acta Angiol., 2003, Vol. 9, No. 4)Tj
24.3637 -91.3463 TD
0.0094 Tc
0 Tw
(www.angiologia.pl)Tj
9 0 0 9 76.5 734.015 Tm
-0.0156 Tc
0.0461 Tw
(The published results of gene therapy are promising)Tj
-1.5733 -1.4433 TD
-0.0151 Tc
0.1215 Tw
([33]. There is unfortunately little knowledge about the)Tj
T*
-0.0157 Tc
0.0799 Tw
[(side effects of this therapy. Some questions arose )]TJ
21.9333 0 TD
-0.001 Tc
0 Tw
(from)Tj
-21.9333 -1.4467 TD
-0.0151 Tc
0.0021 Tw
(the possibility of quick growth of latent and undiagnosed)Tj
0 -1.4433 TD
-0.0149 Tc
0.0166 Tw
[(tumor at the time of therapy. It is unknown what would)]TJ
T*
-0.0155 Tc
0.003 Tw
(be the effect of gene therapy on the blood vessels of the)Tj
0 -1.4467 TD
-0.0152 Tc
-0.0132 Tw
(retina, especially in patients with diabetes mellitus. In the)Tj
0 -1.4433 TD
-0.0127 Tc
0.1389 Tw
[(authors)-14.5( )-16(opinion gene therapy with the plasmid which)]TJ
T*
-0.0155 Tc
-0.0493 Tw
(codes vascular endothelial growth factor may be an alter-)Tj
0 -1.4467 TD
-0.0138 Tc
0.1389 Tw
[(native way of treatment of)-13.8( ischemia in the future, but)]TJ
0 -1.4433 TD
0.0002 Tc
-0.0019 Tw
[(nowadays to little i)15.1(s)15.1( )]TJ
8.9631 0 TD
-0.0149 Tc
-0.0042 Tw
(known about this method.)Tj
/F7 1 Tf
11 0 0 11 138.51 573.635 Tm
0.0036 Tc
0 Tw
(References)Tj
/F2 1 Tf
8 0 0 8 62.34 559.325 Tm
-0.0006 Tc
-0.002 Tw
[(1.)-1294.3(Gardner AW, Thompson PD \(2002\) wiczenia ruchowe)]TJ
2.1262 -1.3763 TD
-0.0005 Tc
0.1156 Tw
(w przewlekym miadycowym niedokrwieniu koczyn)Tj
0 -1.3725 TD
0 Tw
(dolnych. Medycyna po Dyplomie, 11: 2.)Tj
-2.1262 -1.3763 TD
-0.0007 Tc
-0.0302 Tw
[(2.)-1294.4(Noszczyk W, Andziak P \(1998\) Przewleke niedokrwien-)]TJ
2.1262 -1.3763 TD
-0.0009 Tc
0.0679 Tw
(ie koczyn dolnych. Chirurgia ttnic i y obwodowych.)Tj
0 -1.3725 TD
-0.0011 Tc
0.0063 Tw
(Rozdzia 27.1)Tj
-2.1262 -1.3763 TD
0.0017 Tc
0.1375 Tw
[(3.)-1292(Engler RL, Martin J \(1999\) Joint AHA/ESC symposium:)]TJ
2.1262 -1.3763 TD
-0.0006 Tc
0 Tw
(Biorevascularization.)Tj
-2.1262 -1.3725 TD
-0.0103 Tc
-0.0403 Tw
[(4)-10.8(.)-1304(Ferrara N, Houck K, Jakeman L, Leung DW \(1992\) Molec-)]TJ
2.1262 -1.3763 TD
-0.0105 Tc
0.134 Tw
(ular and biological properties of the vascular endothelial)Tj
T*
-0.0107 Tc
0 Tw
(growth factor family of proteins. Endocr Rev, 13: 1832.)Tj
-2.1262 -1.3725 TD
-0.0098 Tc
-0.0687 Tw
[(5)-10.3(.)-1303.5(Dulak J; Jzkowicz A, Ratajska A, Szuba A, Cooke JP, Dem-)]TJ
2.1262 -1.3763 TD
-0.0133 Tc
(biska-Kie A \(2000\) VEGF is efficiently synthesized in spite)Tj
T*
-0.0126 Tc
(of low transfection efficiency of pSG5VEGF plasmids in vas-)Tj
0 -1.3725 TD
-0.0085 Tc
0 Tw
(cular smooth muscle cells. Vascular Medicine, 5: 3340.)Tj
-2.1262 -1.3763 TD
0.0196 Tc
0.1375 Tw
[(6)19.1(.)-1274.1(Dulak J, Jzkowicz A, Dembiska-Kie A, Guevara I,)]TJ
2.1262 -1.3763 TD
0.0141 Tc
0.1105 Tw
(Zdzienicka A, Zmudziska-Grochot D, Florek I, Wj-)Tj
0 -1.3725 TD
0.013 Tc
0.0231 Tw
[(towicz A, Szuba A,)13.6( )]TJ
8.8943 0 TD
-0.0006 Tc
0.024 Tw
(Cook JP \(2000\) Nitric oxide induces)Tj
-8.8943 -1.3763 TD
-0.0034 Tc
-0.0687 Tw
(the synthesis of VEGF by rat vascular smooth muscle cells.)Tj
T*
-0.0004 Tc
0.0012 Tw
(Arterioscler Thromb Vasc Biol, 20: 659666.)Tj
-2.1262 -1.3725 TD
-0.0008 Tc
0.1292 Tw
[(7.)-1294.5(Wartiovaara U, Salven P, Mikkola H et al. \(1998\) Peri-)]TJ
2.1262 -1.3763 TD
-0.0007 Tc
0.0187 Tw
(pheral blood platelets express VEGF-C and VEGF which)Tj
T*
-0.0004 Tc
-0.0198 Tw
(are released during platelet activation. Thromb Haemos-)Tj
0 -1.3725 TD
0 Tw
(tas, 80: 171175.)Tj
-2.1262 -1.3763 TD
-0.0157 Tc
-0.0601 Tw
[(8)-16.2(.)-1309.4(Weltermann A, Wolzt M, Petersmann K, Czerni C, Grasseli)]TJ
2.1262 -1.3763 TD
0.0524 Tw
[(U, Lechner K et al. \(1999\) Large amounts of VEGF at )-18(t)-14.2(h)-14.2(e)]TJ
0 -1.3725 TD
0.0085 Tc
0.1375 Tw
(site of hemostatic plug formation in vivo. Arterioscler)Tj
0 -1.3763 TD
-0.0001 Tc
0 Tw
(Thromb Vasc Biol, 19: 17571760.)Tj
-2.1262 -1.3763 TD
-0.0155 Tc
-0.0519 Tw
[(9)-16(.)-1309.2(Senger DR, Connoly D, Van de Water, Feder L, Dvorak HF)]TJ
2.1262 -1.3725 TD
-0.051 Tw
(\(1990\) Purification and NH2-terminal amino acid se)Tj
21.7575 0 TD
0.001 Tc
0 Tw
(quence)Tj
-21.7575 -1.3763 TD
-0.0104 Tc
0.0021 Tw
(of guinea pig tumor-secreted vascular permeability factor.)Tj
T*
0.0001 Tc
0.0019 Tw
(Cancer Res, 50: 17741778.)Tj
-2.1262 -1.3725 TD
-0.0009 Tc
0.0536 Tw
[(10.)-739.6(Claffey KP, Brown LF, Del Aguila L, Tognazzi K, Yeo K,)]TJ
2.1262 -1.3763 TD
0.0045 Tc
0.1375 Tw
(Manseau EJ, Dvorak HF \(1996\) Expression of vascular)Tj
T*
-0.0008 Tc
-0.0075 Tw
(permeability factor/vascular endothelial growth factor by)Tj
0 -1.3725 TD
-0.0002 Tc
0.0541 Tw
(melanoma cells increases tumor growth. A angiogenesis)Tj
0 -1.3762 TD
-0.0114 Tw
(and experimental metastasis. Cancer Res, 56: 1721781.)Tj
-2.1262 -1.3763 TD
-0.0008 Tc
0.0077 Tw
[(11.)-739.5(Tischer E, Mitchell R, Hartman T, Silva M, Gospodarow-)]TJ
2.1262 -1.3725 TD
-0.0006 Tc
0.0456 Tw
(icz D, Fiddes J, Abraham JA \(1991\) The human gene for)Tj
0 -1.3763 TD
-0.0027 Tc
-0.0687 Tw
(vascular endothelial growth factor. Multiple protein forms)Tj
T*
-0.0123 Tc
(are encoded through alternative exon splicing. J Biol Chem,)Tj
0 -1.3725 TD
0.0007 Tc
0 Tw
(266: 1194711954.)Tj
-2.1262 -1.3763 TD
-0.0006 Tc
0.0172 Tw
[(12.)-739.3(Ferrara N, Davis-Smith T \(1997\) The biology of vascular)]TJ
2.1262 -1.3763 TD
0 Tw
(endothelial growth factor. Endocr Rev, 18: 425.)Tj
-2.1262 -1.3725 TD
0.0217 Tc
0.1375 Tw
[(1)21.4(3)21.4(.)-717(Schaper W \(1993\) Coronary collateral development:)]TJ
32.07 41.25 TD
0.0122 Tc
-0.0687 Tw
(concepts and hypotheses. In: Schaper W, Schaper J, eds.)Tj
0 -1.3763 TD
0.0142 Tc
0 Tw
(Collateral Circulation, 46.)Tj
-2.1263 -1.3763 TD
-0.001 Tc
-0.0688 Tw
[(14.)-739.7(Semenza GL \(1999\) Perspectives on oxygen sensing. Cell,)]TJ
2.1263 -1.3725 TD
0.0003 Tc
0 Tw
(98: 281284.)Tj
-2.1263 -1.3763 TD
-0.0004 Tc
0.0076 Tw
[(15.)-739.1(Namiki A, Brogi E et al. \(1995\) Hypoxia induces vascular)]TJ
2.1263 -1.3763 TD
-0.0005 Tc
0.0604 Tw
(endothelial growth factor in cultured human endothelial)Tj
0 -1.3725 TD
-0.0001 Tc
0 Tw
(cells. J Biol Chem, 270: 3118931195.)Tj
-2.1263 -1.3763 TD
-0.0005 Tc
0.0868 Tw
[(16.)-739.2(Ikeda E, Achen MG, Breier G, Risau W \(1995\) Hypoxia)]TJ
2.1263 -1.3763 TD
-0.0006 Tc
0.0792 Tw
[(induced transcriptional activation and increased mRNA)]TJ
0 -1.3725 TD
-0.0008 Tc
0.1375 Tw
(stability of VEGF in C6 glioma cells. J Biol Chem, 270:)Tj
0 -1.3763 TD
0.0009 Tc
0 Tw
(1976119766.)Tj
-2.1263 -1.3763 TD
0.0093 Tc
-0.0027 Tw
[(1)9(7)9(.)-729.4(Ji YS, Xu Q, Schmedtje JF \(1998\) Hypoxia induces high-)]TJ
2.1263 -1.3725 TD
-0.0007 Tc
-0.0039 Tw
[(-)-12.2(mobility group protein I and transcription of the cycloo-)]TJ
0 -1.3763 TD
-0.0074 Tc
-0.0688 Tw
(xygenase-gene 2 in human vascular endothelium. Circ Res,)Tj
T*
0.0003 Tc
0 Tw
(83: 295304.)Tj
-2.1263 -1.3725 TD
-0.0308 Tc
-0.0404 Tw
[(1)-31.1(8)-31.1(.)-769.5(Kappel A, Ronicke V, Damert A, Flamme I, Risau W, Breier G)]TJ
2.1263 -1.3763 TD
-0.0009 Tc
-0.0322 Tw
[(\()33.9(1999\) Identification of VEGF receptor-2 \(Flk-1\) promot-)]TJ
T*
-0.0002 Tc
0.1133 Tw
[(er enhancer sequences sufficient for angioblast and en-)]TJ
0 -1.3725 TD
0.0134 Tc
0.1375 Tw
(dothelial cell-specific transcription in transgenic mice.)Tj
0 -1.3763 TD
0.0001 Tc
0 Tw
(Blood, 93: 42844292.)Tj
-2.1263 -1.3762 TD
-0.0005 Tc
-0.0181 Tw
[(19.)-739.2(Vincent KA et al. \(2000\) Angiogenesis is induced in a rab-)]TJ
2.1263 -1.3725 TD
-0.0004 Tc
0.036 Tw
(bit model of hindlimb ischemia by naked DNA encoding)Tj
0 -1.3762 TD
-0.001 Tc
0.0563 Tw
(an HIF-1)Tj
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