Overexpression of transforming growth factor-beta 1 in the valvular fibrosis of chronic rheumatic heart disease.
For the purpose of determining the pathogenic role of transforming growth factor-beta1 (TGF-beta 1) in the mechanism of chronic rheumatic heart disease, we evaluated the expression of TGF-beta 1, 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-beta 1 expression was identified in 21 cases (70%) of rheumatic mitral valves, whereas only 3 cases (20%) of the control group showed high TGF-beta 1 expression (p<0.001). Additionally, increased proliferation of myofibroblasts was observed in the rheumatic valves. High TGF-beta1 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-beta 1 expression in mitral valves (p=0.040). In conclusion, an ongoing inflammatory process, the expression of TGF-beta 1, 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.
Kim
Lucia
L
Department of Pathology, Inha University College of Medicine, Incheon, Korea. luciado@inha.ac.kr
Kim
Do Kyun
DK
Yang
Woo Ick
WI
Shin
Dong Hwan
DH
Jung
Ick Mo
IM
Park
Han Ki
HK
Chang
Byung Chul
BC
D000328:Adult; D000368:Aged; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008943:Mitral Valve / Q000473:pathology*; D011509:Proteoglycans / Q000378:metabolism; D012214:Rheumatic Heart Disease / Q000378:metabolism* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000032:analysis / Q000502:physiology*
D011509:Proteoglycans; D053773:Transforming Growth Factor beta1; D003094:Collagen