Pleiotropic effects of transforming growth factor-beta1 on pericardial interstitial cells. Implications for fibrosis and calcification in idiopathic constrictive pericarditis.

摘要

Chronic and permanent constrictive pericarditis represents a serious hemodynamic syndrome that can lead to heart failure unless surgically treated (1). Although a number of factors may cause constriction, idiopathic constrictive pericarditis (ICP) is becoming increasingly prevalent in developed countries (2). Unfortunately, the mechanisms underlying pericardia! fibrosis and calcification in ICP remain poorly understood.Transforming growth factor-beta 1 (TGF-beta 1) plays a key role in many fibrocalcific lesions, including cardiovascular diseases (3). Here, using immunoblotting, we found increased expression of TGF-beta 1 in ICP pericardia (n = 18), and this increased expression was associated with increased collagen/elastin ratio (r = 0.6585, p = 0.0030) and calcification {r= 0.5328, p = 0.0228), suggesting a possible contribution of TGF-beta 1 to pericardial fibrosis and calcification. Real-time reverse transcription-polymerase chain reaction (RT-PCR) demonstrated that the messenger ribonucleic acid (mRNA) levels of collagen I, collagen III, matrix metallopro-teinase (MMP)-2, MMP-8, MMP-9, tissue inhibitor of metallo-proteinase (TIMP)-l, and TIMP-2 were significantly increased in ICP (n = 18) pericardia compared with control pericardia (n = 12), whereas those of elastin, MMP-1, and MMP-13 were decreased (all p < 0.05).