Vol 26, No 6 (2019)
Original articles — Clinical cardiology
Published online: 2018-03-02

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Mast cell derived carboxypeptidase A3 is decreased among patients with advanced coronary artery disease

Łukasz Lewicki1, Janusz Siebert2, Tomasz Koliński3, Karolina Piekarska4, Magdalena Reiwer-Gostomska5, Radosław Targoński6, Piotr Trzonkowski7, Natalia Marek-Trzonkowska8
Pubmed: 29512095
Cardiol J 2019;26(6):680-686.

Abstract

Background: Coronary artery disease (CAD) affects milions of people and can result in myocardial
infarction (MI). Previously, mast cells (MC) have been extensively investigated in the context of hypersensitivity,
however as regulators of the local inflammatory response they can potentially contribute to
CAD and/or its progression. The aim of the study was to assess if serum concentration of MC proteases:
carboxypeptidase A3, cathepsin G and chymase 1 is associated with the extension of CAD and MI.
Methods: The 44 patients with angiographically confirmed CAD (23 subjects with non-ST-segment
elevation MI [NSTEMI] and 21 with stable CAD) were analyzed. Clinical data were obtained as well
serum concentrations of carboxypeptidase A3, cathepsin G and chymase 1 were also measured.
Results: Patients with single vessel CAD had higher serum concentration of carboxypeptidase than
those with more advanced CAD (3838.6 ± 1083.1 pg/mL vs. 2715.6 ± 442.5 pg/mL; p = 0.02). There
were no significant differences in levels of any protease between patients with stable CAD and those with
NSTEMI. Patients with hypertension had ≈2-fold lower serum levels of cathepsin G than normotensive
individuals (4.6 ± 0.9 pg/mL vs. 9.4 ± 5.8 pg/mL; p = 0.001). Cathepsin G levels were also decreased
in sera of the current smokers as compared with non-smokers (3.1 ± 1.2 ng/mL vs. 5.8 ± 1.2 ng/mL,
p = 0.02).
Conclusions: Decreased serum level of carboxypeptidase is a hallmark of more advanced CAD. Lower
serum levels of carboxypeptidase A3 and catepsin G are associated with risk factors of blood vessel damage
suggesting a protective role of these enzymes in CAD.

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References

  1. Kaartinen M, Penttilä A, Kovanen PT. Accumulation of activated mast cells in the shoulder region of human coronary atheroma, the predilection site of atheromatous rupture. Circulation. 1994; 90(4): 1669–1678.
  2. Kaartinen M, Penttilä A, Kovanen PT. Mast cells in rupture-prone areas of human coronary atheromas produce and store TNF-alpha. Circulation. 1996; 94(11): 2787–2792.
  3. Zhao W, Oskeritzian CA, Pozez AL, et al. Cytokine production by skin-derived mast cells: endogenous proteases are responsible for degradation of cytokines. J Immunol. 2005; 175(4): 2635–2642.
  4. Lewicki L, Siebert J, Marek-Trzonkowska N, et al. Elevated Serum Tryptase and Endothelin in Patients with ST Segment Elevation Myocardial Infarction: Preliminary Report. Mediators Inflamm. 2015; 2015: 395173.
  5. Oyamada S, Bianchi C, Takai S, et al. Impact of acute myocardial ischemia reperfusion on the tissue and blood-borne renin-angiotensin system. Basic Res Cardiol. 2010; 105(4): 513–522.
  6. Oyamada S, Bianchi C, Takai S, et al. Chymase inhibition reduces infarction and matrix metalloproteinase-9 activation and attenuates inflammation and fibrosis after acute myocardial ischemia/reperfusion. J Pharmacol Exp Ther. 2011; 339(1): 143–151.
  7. Wei CC, Tian B, Perry G, et al. Differential ANG II generation in plasma and tissue of mice with decreased expression of the ACE gene. Am J Physiol Heart Circ Physiol. 2002; 282(6): H2254–H2258.
  8. Helske S, Syväranta S, Kupari M, et al. Possible role for mast cell-derived cathepsin G in the adverse remodelling of stenotic aortic valves. Eur Heart J. 2006; 27(12): 1495–1504.
  9. Owen CA, Campbell EJ. Angiotensin II generation at the cell surface of activated neutrophils: novel cathepsin G-mediated catalytic activity that is resistant to inhibition. J Immunol. 1998; 160(3): 1436–1443.
  10. Lindstedt KA, Mäyränpää MI, Kovanen PT. Mast cells in vulnerable atherosclerotic plaques--a view to a kill. J Cell Mol Med. 2007; 11(4): 739–758.
  11. Boudier C, Godeau G, Hornebeck W, et al. The elastolytic activity of cathepsin G: an ex vivo study with dermal elastin. Am J Respir Cell Mol Biol. 1991; 4(6): 497–503.
  12. Chatham WW, Blackburn WD, Heck LW. Additive enhancement of neutrophil collagenase activity by HOCl and cathepsin G. Biochem Biophys Res Commun. 1992; 184(2): 560–567.
  13. Wang J, Sjöberg S, Tang TT, et al. Cathepsin G activity lowers plasma LDL and reduces atherosclerosis. Biochim Biophys Acta. 2014; 1842(11): 2174–2183.
  14. Kokkonen JO, Vartiainen M, Kovanen PT. Low density lipoprotein degradation by secretory granules of rat mast cells. Sequential degradation of apolipoprotein B by granule chymase and carboxypeptidase A. J Biol Chem. 1986; 261(34): 16067–16072.
  15. Schwartz LB, Riedel C, Schratz JJ, et al. Localization of carboxypeptidase A to the macromolecular heparin proteoglycan-protein complex in secretory granules of rat serosal mast cells. J Immunol. 1982; 128(3): 1128–1133.
  16. Irani AM, Goldstein SM, Wintroub BU, et al. Human mast cell carboxypeptidase. Selective localization to MCTC cells. J Immunol. 1991; 147(1): 247–253.
  17. Dougherty RH, Sidhu SS, Raman K, et al. Accumulation of intraepithelial mast cells with a unique protease phenotype in T(H)2-high asthma. J Allergy Clin Immunol. 2010; 125(5): 1046–1053.e8.
  18. Lundequist A, Tchougounova E, Abrink M, et al. Cooperation between mast cell carboxypeptidase A and the chymase mouse mast cell protease 4 in the formation and degradation of angiotensin II. J Biol Chem. 2004; 279(31): 32339–32344.
  19. Gilfillan AM, Beaven MA. Regulation of mast cell responses in health and disease. Crit Rev Immunol. 2011; 31(6): 475–529.
  20. Xiang M, Sun J, Lin Y, et al. Usefulness of serum tryptase level as an independent biomarker for coronary plaque instability in a Chinese population. Atherosclerosis. 2011; 215(2): 494–499.
  21. Sata M, Fukuda D. Crucial role of renin-angiotensin system in the pathogenesis of atherosclerosis. J Med Invest. 2010; 57(1-2): 12–25.
  22. da Silva AR, Fraga-Silva RA, Stergiopulos N, et al. Update on the role of angiotensin in the pathophysiology of coronary atherothrombosis. Eur J Clin Invest. 2015; 45(3): 274–287.
  23. Parikh V, Singh M. Possible role of adrenergic component and cardiac mast cell degranulation in preconditioning-induced cardioprotection. Pharmacol Res. 1999; 40(2): 129–137.
  24. Najder A. Sense of coherence, smoking status, biochemical cardiovascular risk factors and body mass in blue collar workers-short report. Am J Mens Health. 2018 [Epub ahead of print]: 1557988317748393.
  25. Caughey GH. Mast cell proteases as protective and inflammatory mediators. Adv Exp Med Biol. 2011; 716: 212–234.
  26. Virdis A, Giannarelli C, Neves MF, et al. Cigarette smoking and hypertension. Curr Pharm Des. 2010; 16(23): 2518–2525.