Local regulation of extracellular matrix structure

The extracellular matrix (ECM) is composed of various collagens, glycosaminoglycans, and elastin bathed by a tissue fluid found throughout the interstitial space. It is this substratum in which fibroblasts and macrophages normally reside, where fibroblast phenotypic transformation occurs, and into which inflammatory cells migrate when called upon during tissue repair. Many diseases, expressed in an organ-specific manner, require organ-specific ECM remodeling. Regulation of fibrillary type I collagen synthesis, whose disproportionate (relative to degradation) accumulation is characteristic of the tissue fibrosis that adversely alters organ function, is therefore of considerable importance. Emerging evidence implicates angiotensin converting enzyme (ACE), found in fibroblast-like cells, and ACE-related peptides, angiotensin II and bradykinin, in serving important regulatory functions that influence wound healing and thereby ECM structure in health and disease. The heart and its collagen matrix have been targeted for discussion in this brief review.