Imbalance between pro-angiogenic and anti-angiogenic factors in rheumatic and mixomatous mitral valves

BACKGROUND: A balance between angiogenic and anti-angiogenic factors is critical in tissue development, tissue repair and homeostasis. Aberrant angiogenesis has been implicated in several pathologic conditions, including valvular heart disease. The aim of this study was to ascertain the pathogenetic role of angiogenesis in rheumatic and mixomatous mitral valve diseases.

METHODS: Leaflets from mixomatous (n=20) and rheumatic (n=20) mitral valves removed from surgical patients, and normal mitral valve (n=6) obtained at autopsy were collected. Immunohistochemical studies were performed on sequential valve sections, evaluating CD31, CD34, α smooth muscle actin (α-SMA), vascular endothelial growth factor (VEGF), VEGF receptor-1 (VEGFR1), VEGF receptor-2 (VEGFR-2), and chondromodulin-I (Chm-I).

RESULTS: Immunohistochemistry revealed significant differences among groups in CD31 (p=0.001), CD34 (p<0.001), α-SMA (p<0.001), VEGF (p<0.001), VEGFR1 (p=0.007), VEGFR2 (p=0.011), and Chm-I (p<0.001) expressions. Rheumatic valves demonstrated a severe up-regulation and down-regulation in pro-angiogenic and anti-angiogenic factors, respectively, compared with mixomatous and normal mitral valves. On the contrary, mixomatous valves showed a significant up-regulation of anti-angiogenic factors with respect to rheumatic and normal valves.

CONCLUSIONS: These findings provide evidence that an imbalance between pro-angiogenic and anti-angiogenic factors is implicated in mitral valve disease. Pro-angiogenic factors are up-regulated in rheumatic disease, while anti-angiogenic ones in mixomatous mitral valves.