Abnormal fibroblast clone--an alternative hypothesis for pathogenesis of rheumatic heart disease.

Fibrosis is an ubiquitous process. Any tissue injury can culminate in fibroblast accumulation and multiplication with collagen synthesis and deposition. A large number of chronic disease states such as rheumatic heart disease, constrictive pericarditis, cirrhosis of the liver, renal interstitial fibrosis, chronic interstitial lung disease are characterized by extensive fibrosis. In many of these patients, when there is no clinical or laboratory evidence of previous injury, it is presumed that the initiating insult/injury had been 'subclinical'. I propose that 1) the fibroblasts can be activated even in the absence of preceding inflammation, 2) it is the type of 'fibroblast clone' in a given individual together with the 'milieu' in a particular tissue/organ which decides the occurrence and severity of subsequent fibrosis. This fibroblast clonal theory adds a new dimension to the pathogenesis of various disease states and may help in identifying those at high-risk and in evolving a unified therapeutic strategy for amelioration of various disorders characterized by extensive fibrosis.