Vol 27, No 6 (2020)
Original Article
Published online: 2019-09-04

open access

Page views 994
Article views/downloads 963
Get Citation

Connect on Social Media

Connect on Social Media

Infiltration of CD68+ cells correlates positively with matrix metalloproteinase 2 expression in the arteries used as aortocoronary bypass grafts. Possible clinical implications

Bartłomiej Perek1, Katarzyna Kowalska2, Bartosz Kempisty23, Mariusz Nawrocki3, Michał Nowicki2, Mateusz Puślecki1, Danuta Ostalska-Nowicka4, Łukasz Szarpak5, Navid Ahmadi1, Agnieszka Malińska2
Pubmed: 31489609
Cardiol J 2020;27(6):817-824.


Background: Late failure of arterial aortocoronary conduits may result from abnormal activity of cells found in the vessel wall, including macrophages. The purpose of this study was to assess if there are any associations between the number of macrophages and overexpression of matrix metalloproteinases (MMPs) in the wall of arterial grafts, as well as their clinical significance.

Methods: This study involved 128 consecutive patients with a mean age of 64.9 ± 9.7 years who underwent elective surgery for coronary artery disease (CAD). The surplus segments of internal thoracic artery (ITA) and radial arteries (RA) were taken for immunohistochemical analysis of macrophage numbers and MMPs expression. The participants who reached the clinical primary end-point (cardiacrelated death, acute coronary syndrome or progression of CAD) had a follow-up angiography.

Results: The mean numbers of macrophages were higher on RA (70 [24; 112]) than ITA cross-sections (44 [24; 59]; p < 0.001). Median expression of both MMP2 and MMP9 were stronger in the ITA than RA cross-sections (p < 0.001). A significant positive correlation of MMP2 expression and a number of macrophages infiltrating the tunica media of arterial segments were noted on both ITA and RA cross-sections. In addition, the arterial segments of the 6 patients who reached clinical end-point had higher numbers of macrophages and stronger MMP2 expression when compared to the rest of the participants.

Conclusions: Macrophage infiltration of arterial wall grafts prior to harvesting may be associated with higher risk of late occlusion and MMP2 might be facilitating this process.

Article available in PDF format

View PDF Download PDF file


  1. Huang F, Lai W, Chan C, et al. Comparison of bypass surgery and drug-eluting stenting in diabetic patients with left main and/or multivessel disease: A systematic review and meta-analysis of randomized and nonrandomized studies. Cardiol J. 2015; 22(2): 123–134.
  2. Shavadia J, Norris CM, Graham MM, et al. Symptomatic graft failure and impact on clinical outcome after coronary artery bypass grafting surgery: Results from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry. Am Heart J. 2015; 169(6): 833–840.
  3. Gaudino M, Benedetto U, Fremes S, et al. Radial-Artery or saphenous-vein grafts in coronary-artery bypass surgery. N Engl J Med. 2018; 378(22): 2069–2077.
  4. Gansera B, Schmidtler F, Angelis I, et al. Patency of internal thoracic artery compared to vein grafts - postoperative angiographic findings in 1189 symptomatic patients in 12 years. Thorac Cardiovasc Surg. 2007; 55(7): 412–417.
  5. Bonacchi M, Prifti E, Maiani M, et al. Perioperative and clinical-angiographic late outcome of total arterial myocardial revascularization according to different composite original graft techniques. Heart Vessels. 2006; 21(2): 69–77.
  6. Cao C, Manganas C, Horton M, et al. Angiographic outcomes of radial artery versus saphenous vein in coronary artery bypass graft surgery: a meta-analysis of randomized controlled trials. J Thorac Cardiovasc Surg. 2013; 146(2): 255–261.
  7. Fonseca DA, Antunes PE, Cotrim MD. Ultrastructural and histomorphologic properties of the internal thoracic artery: implications for coronary revascularization. Coron Artery Dis. 2017; 28(6): 518–527.
  8. Heo SH, Cho CH, Kim HOk, et al. Plaque rupture is a determinant of vascular events in carotid artery atherosclerotic disease: involvement of matrix metalloproteinases 2 and 9. J Clin Neurol. 2011; 7(2): 69–76.
  9. Zhang L, Liao Mf, Tian L, et al. Overexpression of interleukin-1β and interferon-γ in type I thoracic aortic dissections and ascending thoracic aortic aneurysms: possible correlation with matrix metalloproteinase-9 expression and apoptosis of aortic media cells. Eur J Cardiothorac Surg. 2011; 40(1): 17–22.
  10. Li Ya. Correlation analysis of levels of adiponectin and matrix metalloproteinase-9 with stability of coronary heart disease. Technol Health Care. 2015; 23 Suppl 1: S95–S98.
  11. Grzela T, Niderla-Bielinska J, Litwiniuk M, et al. The direct inhibition of MMP-2 and MMP-9 by an enzyme alginogel: a possible mechanism of healing support for venous leg ulcers. J Wound Care. 2014; 23(5): 278–285.
  12. Li TT, Xie Yi, Guo Y, et al. Effect of probucol on vascular remodeling due to atherosclerosis in rabbits: an intravascular ultrasound study. Chin Med J (Engl). 2011; 124(12): 1840–1847.
  13. Aoki T, Kataoka H, Morimoto M, et al. Macrophage-derived matrix metalloproteinase-2 and -9 promote the progression of cerebral aneurysms in rats. Stroke. 2007; 38(1): 162–169.
  14. Ghosh A, Pechota LV, Upchurch GR, et al. Cross-talk between macrophages, smooth muscle cells, and endothelial cells in response to cigarette smoke: the effects on MMP2 and 9. Mol Cell Biochem. 2015; 410(1-2): 75–84.
  15. Otsuka F, Kramer MCA, Woudstra P, et al. Natural progression of atherosclerosis from pathologic intimal thickening to late fibroatheroma in human coronary arteries: A pathology study. Atherosclerosis. 2015; 241(2): 772–782.
  16. Malinska A, Perek B, Buczkowski P, et al. CD68 expression in aortocoronary saphenous vein bypass grafts. Histochem Cell Biol. 2013; 140(2): 183–188.
  17. Perek B, Kowalska K, Kempisty B, et al. Gender and age-related variability of macrophage representation in the internal thoracic artery wall: does it matter? J Biol Regul Homeost Agents. 2018; 32(4): 791–802.
  18. Chung JiH, Jeon HJu, Hong SY, et al. Palmitate promotes the paracrine effects of macrophages on vascular smooth muscle cells: the role of bone morphogenetic proteins. PLoS One. 2012; 7(2): e29100.
  19. Chatrou MLL, Cleutjens JP, van der Vusse GJ, et al. Intra-Section analysis of human coronary arteries reveals a potential role for micro-calcifications in macrophage recruitment in the early stage of atherosclerosis. PLoS One. 2015; 10(11): e0142335.
  20. Hinojosa-Amaya JM, Villarreal-Silva EE, Elizondo-Omana RE, et al. Conduits for myocardial revascularization grafts: The importance of morphology and imaging. Med Univ. 2010; 47(12): 115–119.
  21. Ruengsakulrach P, Sinclair R, Komeda M, et al. Comparative histopathology of radial artery versus internal thoracic artery and risk factors for development of intimal hyperplasia and atherosclerosis. Circulation. 1999; 100(19 Suppl): II139–II144.
  22. Perek B, Malinska A, Misterski M, et al. Preexisting high expression of matrix metalloproteinase-2 in tunica media of saphenous vein conduits is associated with unfavorable long-term outcomes after coronary artery bypass grafting. Biomed Res Int. 2013; 2013: 730721.
  23. Turner NA, Hall KT, Ball SG, et al. Selective gene silencing of either MMP-2 or MMP-9 inhibits invasion of human saphenous vein smooth muscle cells. Atherosclerosis. 2007; 193(1): 36–43.
  24. Perek B, Malińska A, Ostalska-Nowicka D, et al. Cytokeratin 8 in venous grafts: a factor of unfavorable long-term prognosis in coronary artery bypass grafting patients. Cardiol J. 2013; 20(6): 583–591.
  25. Toth M, Sohail A, Fridman R. Assessment of gelatinases (MMP-2 and MMP-9) by gelatin zymography. Methods Mol Biol. 2012; 878: 121–135.
  26. Leber TM, Balkwill FR. Zymography: a single-step staining method for quantitation of proteolytic activity on substrate gels. Anal Biochem. 1997; 249(1): 24–28.