Role of type IV collagen and matrix metalloproteinase-9 in remodeling of the left ventricular in coronary artery disease

Currently, the analysis of the fibrosis severity during the restructuring of the surrounding extracellular matrix (ECM) is studied in most of the research works devoted to “cardiac remodeling”. At the same time, the role of the basal membrane of cardiomyocytes in heart diseases was not studied. The basal membrane of cardiomyocytes is a highly organized layer of the ECM which is located on the outer side of the sarcolemma. Degradation of ECM components is carried out by different types of matrix metalloproteinases (MMP), which have proteolytic activity and are actively involved in the process of ECM remodeling, destroying its components such as collagen, elastin, fibronectin, glycosaminoglycans and other structural components.

Aim. To evaluate the ECM status in patients with coronary artery disease and its effect on left ventricular myocardial remodeling.

Material and methods. Morphological and immunohistochemical (IHC) examination of left ventricular myocardial biopsies was performed in 16 patients undergoing left ventricular reconstruction in combination with coronary artery bypass grafting.

Results. The IHC study revealed the accumulation of matrix metalloproteinase-9 in the cytoplasm of cardiomyocytes. This accumulation was combined with partial or complete destruction of the basal membranes (BM) of cardiomyocytes formed by type IV collagen.

Conclusion. Type IV collagen destruction in basal membranes of left ventricular cardiomyocyteswasrevealed. It iscausedbytheactionofmatrixmetalloproteinase-9, which accumulates in the cell cytoplasm.

1. Assayag P, Carré F, Chevalier B, et al. Compensated cardiac hypertrophy: arrhythmogenicity and the new myocardial phenotype I fibrosis. Cardiovascular Research 1997; 4: 439–444. doi.org/10.1016/S0008-6363(97)00073-4.

2. Weber KT. Wound Healing in Cardiovascular Disease. Armonk, NY: Futura 1997; 535-95.

3. Silver MA, Christian R, Brilla G, et al. Reactive and reparative fibrillar collagen remodelling in the hypertrophied rat left ventricle: two experimental models of myocardial fibrosis. Cardiovascular Research 1990; 9: 741–747. doi.org/10.1093/cvr/24.9.741.

4. Farhadian F, Contard F, Sabri A, et al. Fibronectin and basement membrane in cardiovascular organogenesis and disease pathogenesis. Cardiovascular Research 1996; 32 (3): 433-42. doi:10.1016/0008-6363(96)00119-8.

5. Weber KT, Sun Y, Tyagi SC, et al. Collagen Network of the Myocardium: Function, Structural Remodeling and Regulatory Mechanisms. Journal of Molecular and Cellular Cardiology 1994; 3: 279-292. doi.org/10.1006/jmcc.1994.1036.

6. Lamas GA, Pfeffer MA. Left ventricular remodeling after acute myocardial infarction: clinical course and beneficial effects of angiotensin; converting enzyme inhibition. Am Heart J 1991; 4: 1194–1202. doi.org/10.1016/0002-8703(91)90682-8.

7. Sabbah HN, Goldstein S. Ventricular remodelling: consequences and therapy. Eur Heart J 1993; 14: 24–29. DOI: 10.1093/eurheartj/14.suppl_C.24.

8. Coux A, Lindsey ML, Villarreal F, et al. Myocardial matrix metalloproteinase-2: inside out and upside down. Journal of Molecular and Cellular Cardiology 2014; 77: 64-72. https://doi.org/10.1016/j.yjmcc.2014.09.016.

9. Wilson EM, Spinale FG. Myocardial remodelling and matrix metallotxoteinases in heart failure: turmoil within the interstitium. Journal Annals of Medicine 2001; 9: 33. doi.org/10.3109/07853890109002108.

10. Lowe JS, Anderson PG. Human Histology (Fourth Edition), Support Cells and the Extracellular Matrix 2015; p. 440. ISBN: 978-0-323-61279-1.