Matrix metalloproteinases in primary culture of cardiomyocytes

Abstract

The highly organized contractile apparatus of cardiomyocytes in heart tissue allows for their continuous contractility, whereas extracellular matrix components are synthesized and spatially organized by fibroblasts and endothelial cells. However, reorganization of the cardiomyocyte contractile apparatus occurs upon their 2D cultivation, which is accompanied by transient loss of their contractility and acquired capability of extracellular matrix synthesis (Bildyug, N. B., and Pinaev, G. P. (2013) Tsitologiya, 55, 713-724). In this study, matrix metalloproteinases were investigated at different times of cardiomyocyte 2D cultivation and 3D cultivation in collagen gels. It was found that cardiomyocytes in 2D culture synthesize matrix metalloproteinases MMP-2 and MMP-9, wherein their amount varies with the cultivation time. The peak MMP-9 amount is at early cultivation time, when the reorganization of cardiomyocyte contractile apparatus occurs, and the MMP-2 peak precedes the recovery of the initial organization of their contractile apparatus. Upon cardiomyocyte cultivation in 3D collagen gels, in which case their contractile apparatus does not rearrange, a steady small amount of MMP-2 and MMP-9 is observed. These data indicate that the cardiomyocyte contractile apparatus reorganization in culture is associated with synthesis and spatial organization of their own extracellular matrix.

The impact of aging on cardiac extracellular matrix

“…Reactive oxygen species (ROS) production resulting from impaired mitochondrial function stimulates hypoxia inducible factor 1 activation (Liu and Finkel 2014). Cardiomyocytes contribute to ECM remodeling by expressing collagen type IV (Eghbali et al 1989a), MMP-2, -9, -14, and all TIMPs subtypes (Bildyug et al 2015; Riches et al 2009; Vanhoutte and Heymans 2010). …”

Melatonin ameliorates periodontitis‐related inflammatory stress at cardiac left ventricular tissues in rats

“…In another supporting study with a similar methodology, we revealed that periodontitis causes degenerations in cellular and vascular structures and significant inflammatory cell accumulation around vascular structures in left ventricular heart tissue 3 . MMPs are released by various cells such as cardiomyocytes, endothelial cells, fibroblasts, heart associated neutrophils, and macrophages 37 . Nuclear factor‐κB (NF‐κB) is shown to be among the main regulators of MMP‐9 from these cells 38,39 .…”

“…3 MMPs are released by various cells such as cardiomyocytes, endothelial cells, fibroblasts, heart associated neutrophils, and macrophages. 37 Nuclear factor-B (NF-B) is shown to be among the main regulators of MMP-9 from these cells. 38,39 In our study on heart tissue 3 and in a study on aorta by Miyajima et al 40 experimental periodontitis noted to significantly increase the p65 NF-B expression.…”

Investigation of association of genetic variant rs3918242 of matrix metalloproteinase-9 with hypertension, myocardial infarction and progression of ventricular dysfunction in Irish Caucasian patients with diabetes: a report from the STOP-HF follow-up programme

“…The major regulators of cardiovascular ECM are matrix metalloproteinases (MMPs), in particular the gelatinases MMP-2, MMP-9 and their tissue inhibitors [7,8]. MMP-9 is of particular importance and is a zinc dependent endopeptidase enzyme, which is expressed in a broad range of cardiovascular cell types, including cardiomyocytes, cardiac fibroblasts, vascular endothelial cells and inflammatory cells [9,10].…”