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Vol 26, No 3 (2020)
Research paper
Published online: 2021-01-07

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Impact of risk factors on serum levels of vasoactive substances in patients with peripheral arterial occlusive disease at different Fontaine’s stages

Sasa Dragic12, Danica Momcicevic1, Biljana Zlojutro1, Milka Jandric1, Tijana Kovacevic3, Vlado Djajic4, Aleksandar Gajic5, Goran Talic5, Pedja Kovacevic1
Acta Angiologica 2020;26(3):102-107.

Abstract

Introduction: There is a bulk of literature data on the physiological roles of nitric oxide (NO) and endothelin-
1 (ET-1), but many facts remain unknown, especially in certain diseases such as peripheral arterial disease.

Material and methods: This is an observational cross-sectional study. The subjects were patients diagnosed
with PAD. Serum levels of NO and ET-1 were determined for all patients, and statistical data processing was
performed according to the set goals.

Results: The study included 64 patients with mean age 60.2 ± 12.7 years, mostly in stage II PAD according
to Fontain (46.9%). Statistical analysis failed to determine a significant difference in serum NO or ET-1 values
with respect to disease stage, sex, and body mass index (BMI). Certain oscillations were found in the mean
values of NO related to smoking and diabetes but without statistical significance. There were also oscillations
in the values of ET-1, with higher levels found in women, smokers and non-diabetics in whom this difference
reached statistical significance (p = 0.041).

Conclusion: Serum levels of NO and ET-1 in this study show some causal relationship with certain risk factors for
PAD such as diabetes and smoking, but additional research is needed to fully understand their effects and interactions.

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References

  1. Bourque SL, Davidge ST, Adams MA. The interaction between endothelin-1 and nitric oxide in the vasculature: new perspectives. Am J Physiol Regul Integr Comp Physiol. 2011; 300(6): R1288–R1295.
  2. Matschke K, Jung F. Regulation of the myocardial microcirculation. Clin Hemorheol Microcirc. 2008; 39(1-4): 265–279.
  3. Sun HJ, Wu ZY, Nie XW, et al. Role of Endothelial Dysfunction in Cardiovascular Diseases: The Link Between Inflammation and Hydrogen Sulfide. Front Pharmacol. 2019; 10: 1568.
  4. Stanek A, Fazeli B, Bartuś S, et al. The Role of Endothelium in Physiological and Pathological States: New Data. Biomed Res Int. 2018; 2018: 1098039.
  5. Stankevicius E, Kevelaitis E, Vainorius E, et al. [Role of nitric oxide and other endothelium-derived factors]. Medicina (Kaunas). 2003; 39(4): 333–341.
  6. Giaid A, Saleh D. Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N Engl J Med. 1995; 333(4): 214–221.
  7. Herman WH, Simonson MS. Nuclear signaling by endothelin-1. J Biol Chem. 1995; 270: 11654–61.
  8. Taylor C, Moncada S. Nitric oxide, cytochrome C oxidase, and the cellular response to hypoxia. Arteriosclerosis, Thrombosis, and Vascular Biology. 2010; 30(4): 643–647.
  9. Khimji AK, Rockey DC. Endothelin -- biology and disease. Cell Signal. 2010; 22(11): 1615–1625.
  10. Krüger-Genge A, Blocki A, Franke RP, et al. Vascular endothelial cell biology: an update. Int J Mol Sci. 2019; 20(18).
  11. Black SM, Kumar S, Wiseman D, et al. Oxidative and nitrosative stress in pediatric pulmonary hypertension: roles of endothelin-1 and nitric oxide. Vascul Pharmacol. 2006; 45(5): 308–316.
  12. Pollock JS, Pollock DM. Endothelin and NOS1/nitric oxide signaling and regulation of sodium homeostasis. Curr Opin Nephrol Hypertens. 2008; 17(1): 70–75.
  13. Kester M, Simonson MS, McDermott RG, et al. Endothelin stimulates phosphatidic acid formation in cultured rat mesangial cells: role of a protein kinase C-regulated phospholipase D. J Cell Physiol. 1992; 150(3): 578–585.
  14. Ridker P, Cushman M, Stampfer M, et al. Plasma concentration of C-reactive protein and risk of developing peripheral vascular disease. Circulation. 1998; 97(5): 425–428.
  15. Thorin E, Clozel M. The cardiovascular physiology and pharmacology of endothelin-1. Advances in Pharmacology. 2010: 1–26.
  16. Jain A, Coffey C, Mehrotra V, et al. Endothelin-1 traps as a potential therapeutic tool: from diabetes to beyond? Drug Discov Today. 2019; 24(9): 1937–1942.
  17. Weng YH. Alteration of nitric oxide gas on gene expression of endothelin-1 and endothelial nitric oxide synthase by a time-and dose-dependent manner in human endothelial cells. The Chinese Journal of Physiology. 2009; 52(2): 1–6.
  18. Goel A, Su B, Flavahan S, et al. Increased endothelial exocytosis and generation of endothelin-1 contributes to constriction of aged arteries. Circ Res. 2010; 107(2): 242–251.
  19. Veves A, Akbari CM, Primavera J, et al. Endothelial dysfunction and the expression of endothelial nitric oxide synthetase in diabetic neuropathy, vascular disease, and foot ulceration. Diabetes. 1998; 47(3): 457–463.
  20. Eriksson A, Harmelen Vv, Stenson BM, et al. Endothelin-1 stimulates human adipocyte lipolysis through the ETA receptor. International Journal of Obesity. 2008; 33(1): 67–74.
  21. van Harmelen V, Eriksson A, Aström G, et al. Vascular peptide endothelin-1 links fat accumulation with alterations of visceral adipocyte lipolysis. Diabetes. 2008; 57(2): 378–386.
  22. Katsiki N, Papadopoulou SK, Fachantidou AI, et al. Smoking and vascular risk: are all forms of smoking harmful to all types of vascular disease? Public Health. 2013; 127(5): 435–441.
  23. Li J, Cui R, Eshak ES, et al. for CIRCS investigators. Association of cigarette smoking with radial augmentation index: the Circulatory Risk in Communities Study (CIRCS). Hypertens Res. 2018; 41(12): 1054–1062.
  24. Messner B, Bernhard D. Smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis. Arterioscler Thromb Vasc Biol. 2014; 34(3): 509–515.
  25. Park JM, Chang KH, Park KH, et al. Differential effects between cigarette total particulate matter and cigarette smoke extract on blood and blood vessel. Toxicol Res. 2016; 32(4): 353–358.
  26. Shimosato T, Geddawy A, Tawa M, et al. Chronic administration of nicotine-free cigarette smoke extract impaired endothelium-dependent vascular relaxation in rats via increased vascular oxidative stress. J Pharmacol Sci. 2012; 118(2): 206–214.
  27. Carlo WF, Villamor E, Ambalavanan N, et al. Chronic exposure to cigarette smoke extract impairs endothelium-dependent relaxation of chicken embryo pulmonary arteries. Biol Neonate. 2001; 80(3): 247–250.
  28. Ota Y, Kugiyama K, Sugiyama S, et al. Impairment of endothelium-dependent relaxation of rabbit aortas by cigarette smoke extract--role of free radicals and attenuation by captopril. Atherosclerosis. 1997; 131(2): 195–202.
  29. Bossard M, Pumpol K, van der Lely S, et al. Plasma endothelin-1 and cardiovascular risk among young and healthy adults. Atherosclerosis. 2015; 239(1): 186–191.
  30. Hansson GK. Inflammation, atherosclerossis and coronary arthery disesae. N Engl J Med. 2005; 352: 1685–1695.
  31. Haak T, Jungmann E, Raab C, et al. Elevated endothelin-1 levels after cigarette smoking. Metabolism. 1994; 43(3): 267–269.
  32. Cao L, Zhang Y, Cao YX, et al. Cigarette smoke upregulates rat coronary artery endothelin receptors in vivo. PLoS One. 2012; 7(3): e33008.
  33. Ferri C, Carlomagno A, Coassin S, et al. Circulating endothelin-1 levels increase during euglycemic hyperinsulinemic clamp in lean NIDDM men. Diabetes Care. 1995; 18(2): 226–233.
  34. Sarangi S, Srikant B, Rao DV, et al. Correlation between peripheral arterial disease and coronary artery disease using ankle brachial index-a study in Indian population. Indian Heart J. 2012; 64(1): 2–6.
  35. Wojtasik-Bakalarz J, Ruzsa Z, Rakowski T, et al. Impact of coronary artery disease and diabetes mellitus on the long-term follow-up in patients after retrograde recanalization of the femoropopliteal arterial region. J Diabetes Res. 2019; 2019: 6036359.
  36. Myslinski W, Stanek A, Feldo M, et al. Ankle-brachial index as the best predictor of first acute coronary syndrome in patients with treated systemic hypertension. Biomed Res Int. 2020; 2020: 6471098.