Mechanism of matrix accumulation and glomerulosclerosis in spontaneously hypertensive rats :

Human tissue inhibitor of metalloproteinases-1 (TIMP-1), but not TIMP-2, has potent growth-promoting activity for a wide range of human and bovine cells. TIMP-1 seems to be a new cell-growth factor in serum and to stimulate the cells independently of its inhibitory activity.

Extracellular matrix provides a structural, chemical, and mechanical substrate that is essential in cardiac development, growth, and responses to pathophysiological signals. Transmembrane receptors termed integrins provide a dynamic interaction of environmental cues and intracellular events. Integrins orchestrate multiple functions in the intact organism including organogenesis, regulation of gene expression, cell proliferation, differentiation, migration, and death. They are expressed in all cellular components of the cardiovascular system, including the vasculature, blood, cardiac myocytes and nonmuscle cardiac cells. The focus of this review will be on the role of integrins in the myocardium. We will provide background on integrin structure and function, discuss how the expression of integrins is critical to the form and function of the developing and postnatal myocardium, and review the known data on integrins as signaling molecules in the heart. Finally, we will offer insights to the future research directions into this important family of extracellular matrix receptors in the myocardium.