Overexpression of Transforming Growth Factor-β1 in the Valvular Fibrosis of Chronic Rheumatic Heart Disease

For the purpose of determining the pathogenic role of transforming growth factor-β1 (TGF-β1) in the mechanism of chronic rheumatic heart disease, we evaluated the expression of TGF-β1, proliferation of myofibroblasts, and changes in extracellular matrix components including collagen and proteoglycan in 30 rheumatic mitral valves and in 15 control valves. High TGF-β1 expression was identified in 21 cases (70%) of rheumatic mitral valves, whereas only 3 cases (20%) of the control group showed high TGF-β1 expression (p<0.001). Additionally, increased proliferation of myofibroblasts was observed in the rheumatic valves. High TGF-β1 expression positively correlated with the proliferation of myofibroblasts (p=0.004), valvular fibrosis (p<0.001), inflammatory cell infiltration (p=0.004), neovascularization (p=0.007), and calcification (p<0.001) in the valvular leaflets. The ratio of proteoglycan to collagen deposition inversely correlated with TGF-β1 expression in mitral valves (p=0.040). In conclusion, an ongoing inflammatory process, the expression of TGF-β1, and proliferation of myofibroblasts within the valves have a potential role in the valvular fibrosis, calcification, and changes in the extracellular matrix that lead to the scarring sequelae of rheumatic heart disease.