Vol 59, No 1 (2021)
Original paper
Published online: 2021-02-08

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Relationship between calcification, atherosclerosis and matrix proteins in the human aorta

Aleksandra Kuzan1, Jerzy Wisniewski2, Krzysztof Maksymowicz3, Magdalena Kobielarz4, Andrzej Gamian15, Agnieszka Chwilkowska6
Pubmed: 33560515
Folia Histochem Cytobiol 2021;59(1):8-21.

Abstract

Introduction. Extracellular matrix (ECM) proteins have been associated with atherosclerotic complications, such as plaque rupture, calcification and aneurysm. It is not clear what role different types of collagen play in the pathomechanism of atherosclerosis. The aim of the study was to analyze the content of elastin and major types of collagen in the aortic wall and how they associated are with course of atherosclerosis. Material and methods. In this work we present six biochemical parameters related to ECM proteins and collagen-specific amino acids (collagen type I, III, and IV, elastin, proline and hydroxyproline) analyzed in 106 patients’ aortic wall specimens characterized by different degree of atherosclerosis. Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry (LC/ESI-MS/MS), ELISA and immunohistochemical methods were used. The severity of atherosclerosis was assessed on the six-point scale of the American Heart Association, taking into account the number and location of foam cells, the presence of a fatty core, calcium deposits and other characteristic atherosclerotic features.

Results. The results show that there is a relationship between the content of collagen-specific amino acids and development of atherosclerosis. The degree of atherosclerotic lesions was negatively correlated with the content of proline, hydroxyproline and the ratio of these two amino acids. Calcium deposits and surrounding tissue were compared and it was demonstrated that the ratio of type I collagen to type III collagen was higher in the aortic tissue than in aortic calcification areas, while the ratio of collagen type III to elastin was smaller in the artery than in the calcium deposits. Conclusions. We suggest that increase in collagen type III presence in the calcification matrix may stem from disorders in the structure of the type I and III collagen fibers. These anomalous fibers are likely to favor accumulation of the calcium salts, an important feature of the process of atheromatosis.

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References

  1. Xu J, Shi GP. Vascular wall extracellular matrix proteins and vascular diseases. Biochim Biophys Acta. 2014; 1842(11): 2106–2119.
  2. Rekhter M. Collagen synthesis in atherosclerosis: too much and not enough. Cardiovascular Research. 1999; 41(2): 376–384.
  3. Lan TH, Huang XQ, Tan HM. Vascular fibrosis in atherosclerosis. Cardiovasc Pathol. 2013; 22(5): 401–407.
  4. Geary RL, Wong JM, Rossini A, et al. Expression profiling identifies 147 genes contributing to a unique primate neointimal smooth muscle cell phenotype. Arterioscler Thromb Vasc Biol. 2002; 22(12): 2010–2016.
  5. Chiong T, Cheow ESH, Woo CC, et al. Aortic Wall Extracellular Matrix Proteins Correlate with Syntax Score in Patients Undergoing Coronary Artery Bypass Surgery. Open Cardiovasc Med J. 2016; 10: 48–56.
  6. Libby P, Aikawa M. Stabilization of atherosclerotic plaques: new mechanisms and clinical targets. Nat Med. 2002; 8(11): 1257–1262.
  7. Foote CA, Castorena-Gonzalez JA, Ramirez-Perez FI, et al. Arterial Stiffening in Western Diet-Fed Mice Is Associated with Increased Vascular Elastin, Transforming Growth Factor-β, and Plasma Neuraminidase. Front Physiol. 2016; 7: 285.
  8. Asciutto G, Dias NV, Edsfeldt A, et al. Low elastin content of carotid plaques is associated with increased risk of ipsilateral stroke. PLoS One. 2015; 10(3): e0121086.
  9. Shami A, Gonçalves I, Hultgårdh-Nilsson A. Collagen and related extracellular matrix proteins in atherosclerotic plaque development. Curr Opin Lipidol. 2014; 25(5): 394–399.
  10. Greenwald SE. Ageing of the conduit arteries. J Pathol. 2007; 211(2): 157–172.
  11. Stary HC, Chandler AB, Dinsmore RE, et al. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Arterioscler Thromb Vasc Biol. 1995; 15(9): 1512–1531.
  12. Stary HC, Blankenhorn DH, Chandler AB, et al. A definition of the intima of human arteries and of its atherosclerosis-prone regions. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Arterioscler Thromb. 1992; 12(1): 120–134.
  13. Stary HC, Chandler AB, Glagov S, et al. A definition of initial, fatty streak, and intermediate lesions of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Arterioscler Thromb. 1994; 14(5): 840–856.
  14. Järveläinen H, Sainio A, Koulu M, et al. Extracellular matrix molecules: potential targets in pharmacotherapy. Pharmacol Rev. 2009; 61(2): 198–223.
  15. Duprez DA, Gross MD, Ix JH, et al. Collagen biomarkers predict new onset of hypertension in normotensive participants: the Multi-Ethnic Study of Atherosclerosis. J Hypertens. 2018; 36(11): 2245–2250.
  16. Wang H, Liu D, Zhang H. Investigation of the Underlying Genes and Mechanism of Macrophage-Enriched Ruptured Atherosclerotic Plaques Using Bioinformatics Method. J Atheroscler Thromb. 2019; 26(7): 636–658.
  17. Holm Nielsen S, Jonasson L, Kalogeropoulos K, et al. Exploring the role of extracellular matrix proteins to develop biomarkers of plaque vulnerability and outcome. J Intern Med. 2020; 287(5): 493–513.
  18. Kuzan A, Chwiłkowska A, Maksymowicz K, et al. Advanced glycation end products as a source of artifacts in immunoenzymatic methods. Glycoconj J. 2018; 35(1): 95–103.
  19. Kuzan A, Chwiłkowska A, Pezowicz C, et al. The content of collagen type II in human arteries is correlated with the stage of atherosclerosis and calcification foci. Cardiovasc Pathol. 2017; 28: 21–27.
  20. Briones AM, Salaices M, Vila E. Mechanisms underlying hypertrophic remodeling and increased stiffness of mesenteric resistance arteries from aged rats. J Gerontol A Biol Sci Med Sci. 2007; 62(7): 696–706.
  21. Aikawa M, Rabkin E, Okada Y, et al. Lipid lowering by diet reduces matrix metalloproteinase activity and increases collagen content of rabbit atheroma: a potential mechanism of lesion stabilization. Circulation. 1998; 97(24): 2433–2444.
  22. Abdelhalim MA, Siddiqi NJ, Alhomida AS, et al. The changes in various hydroxyproline fractions in aortic tissue of rabbits are closely related to the progression of atherosclerosis. Lipids Health Dis. 2010; 9: 26.
  23. Sakalihasan N, Heyeres A, Nusgens BV, et al. Modifications of the extracellular matrix of aneurysmal abdominal aortas as a function of their size. Eur J Vasc Surg. 1993; 7(6): 633–637.
  24. Kong CH, Lin XY, Woo CC, et al. Characteristics of aortic wall extracellular matrix in patients with acute myocardial infarction: tissue microarray detection of collagen I, collagen III and elastin levels. Interact Cardiovasc Thorac Surg. 2013; 16(1): 11–15.
  25. Cantini C, Kieffer P, Corman B, et al. Aminoguanidine and aortic wall mechanics, structure, and composition in aged rats. Hypertension. 2001; 38(4): 943–948.
  26. Sindram D, Martin K, Meadows JP, et al. Collagen-elastin ratio predicts burst pressure of arterial seals created using a bipolar vessel sealing device in a porcine model. Surg Endosc. 2011; 25(8): 2604–2612.
  27. Katsuda S, Okada Y, Minamoto T, et al. Collagens in human atherosclerosis. Immunohistochemical analysis using collagen type-specific antibodies. Arterioscler Thromb. 1992; 12(4): 494–502.
  28. Shekhonin BV, Domogatsky SP, Idelson GL, et al. Relative distribution of fibronectin and type I, III, IV, V collagens in normal and atherosclerotic intima of human arteries. Atherosclerosis. 1987; 67(1): 9–16.
  29. Jing L, Li L, Ren X, et al. Role of Sortilin and Matrix Vesicles in Nε-Carboxymethyl-Lysine-Induced Diabetic Atherosclerotic Calcification. Diabetes Metab Syndr Obes. 2020; 13: 4141–4151.
  30. Tsai CH, Lin LY, Lin YH, et al. Abdominal aorta calcification predicts cardiovascular but not non-cardiovascular outcome in patients receiving peritoneal dialysis: A prospective cohort study. Medicine (Baltimore). 2020; 99(37): e21730.
  31. Kuga T, Esato K, Zempo N, et al. Detection of type III collagen fragments in specimens of abdominal aortic aneurysms. Surg Today. 1998; 28(4): 385–390.
  32. Lui PPY, Chan LS, Lee YW, et al. Sustained expression of proteoglycans and collagen type III/type I ratio in a calcified tendinopathy model. Rheumatology (Oxford). 2010; 49(2): 231–239.
  33. Volk SW, Shah SR, Cohen AJ, et al. Type III collagen regulates osteoblastogenesis and the quantity of trabecular bone. Calcif Tissue Int. 2014; 94(6): 621–631.
  34. Asgari M, Latifi N, Heris HK, et al. In vitro fibrillogenesis of tropocollagen type III in collagen type I affects its relative fibrillar topology and mechanics. Sci Rep. 2017; 7(1): 1392.
  35. Busch A, Hoffjan S, Bergmann F, et al. Vascular type Ehlers-Danlos syndrome is associated with platelet dysfunction and low vitamin D serum concentration. Orphanet J Rare Dis. 2016; 11(1): 111.
  36. Stary HC, Chandler AB, Dinsmore RE, et al. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation. 1995; 92(5): 1355–1374.
  37. Lee JS, Basalyga DM, Simionescu A, et al. Elastin calcification in the rat subdermal model is accompanied by up-regulation of degradative and osteogenic cellular responses. Am J Pathol. 2006; 168(2): 490–498.
  38. Qin X, Corriere MA, Matrisian LM, et al. Matrix metalloproteinase inhibition attenuates aortic calcification. Arterioscler Thromb Vasc Biol. 2006; 26(7): 1510–1516.
  39. Pereira L, Lee SY, Gayraud B, et al. Pathogenetic sequence for aneurysm revealed in mice underexpressing fibrillin-1. Proc Natl Acad Sci U S A. 1999; 96(7): 3819–3823.
  40. Bailey M, Pillarisetti S, Jones P, et al. Involvement of matrix metalloproteinases and tenascin-C in elastin calcification. Cardiovasc Pathol. 2004; 13(3): 146–155.
  41. Reimann C, Brangsch J, Colletini F, et al. Molecular imaging of the extracellular matrix in the context of atherosclerosis. Adv Drug Deliv Rev. 2017; 113: 49–60.
  42. Chen W, Cormode DP, Vengrenyuk Y, et al. Collagen-specific peptide conjugated HDL nanoparticles as MRI contrast agent to evaluate compositional changes in atherosclerotic plaque regression. JACC Cardiovasc Imaging. 2013; 6(3): 373–384.
  43. Kassam HA, Bahnson EM, Cartaya A, et al. Pharmacokinetics and biodistribution of a collagen-targeted peptide amphiphile for cardiovascular applications. Pharmacol Res Perspect. 2020; 8(6): e00672.
  44. Zheng J, Li Q, He L, et al. Protocatechuic Acid Inhibits Vulnerable Atherosclerotic Lesion Progression in Older Apoe-/- Mice. J Nutr. 2020; 150(5): 1167–1177.
  45. Tomosugi N, Yamamoto S, Takeuchi M, et al. Effect of Collagen Tripeptide on Atherosclerosis in Healthy Humans. J Atheroscler Thromb. 2017; 24(5): 530–538.