CONNECTIVE-TISSUE - A METABOLIC ENTITY

The heart is composed of parenchyma (cardiac myocytes) and stroma (con nective tissue), Stroma is presumed inert and therefore little attenti on has been paid to its regulation. Contrary to this notion, evidence presented here raises the possibility that connective tissue is a meta bolically active entity capable of regulating peptide hormone generati on and degradation and these hormones, in an autocrine manner, regulat e collagen turnover. This concept has evolved from quantitative in vit ro autoradiography (using I-125-351A), which localized angiotensin con verting enzyme (ACE) binding density within the heart, A heterogenous distribution was found, Low-density ACE is present within atria and ve ntricles. At sites of high collagen turnover, such as valve leaflets, adventitia and fibrous tissue of diverse etiologic origins, ACE bindin g density is high and independent of circulating angiotensin II, ACE-p roducing cells at these sites, identified by monoclonal ACE antibody a nd I-125-351A binding, include fibroblast-like alpha actin-containing cells that express the transcript for type I collagen (it? situ hybrid ization). Receptor-ligand binding for angiotensin II and bradykinin is found in fibrous tissue, where these peptides may provide for a recip rocal regulation of fibroblast collagen turnover. Connective tissue fo rmation is attenuated by ACE inhibition or antagonism of type I angiot ensin II receptor, Thus, emerging evidence raises the possibility that stroma and its cellular constituents is a dynamic, metabolically acti ve entity regulating its own peptide hormone composition and, in turn, its turnover of fibrillar collagen.