| Abstract | Background: Although cardiologists and cardiac surgeons encounter aortic valve stenosis on a frequent basis, the molecular biology of cuspal calcification is poorly understood. Now, there is compelling histopathologic data suggesting that apoptosis is involved in calcification of degenerative stenotic aortic valves. Little is known about its contribution to calcification of rheumatic valves.
The aim of this study was to investigate the possible role of apoptosis in cuspal calcification in both rheumatic and degenerative aortic valve stenosis.
Material and Methods: The study population included 20 patients undergoing aortic valve replacement for aortic valve stenosis. Ten cases were rheumatic (age 28 ± 8.6 years) and ten cases were degenerative (age 65.3 ±7.4 years). The severity of aortic valve disease was determined preoperatively by echocardiography. We performed histological, histochemical and immunohistochemical studies on formalin-fixed, paraffin- embedded stenotic aortic valve leaflets removed during aortic valve replacement. Masson trichrome stain was performed to highlight fibrotic changes. Immunohistochemical studies were performed according to avidin-biotin-peroxidase complex (ABC) method using polyclonal rabbit antihuman Bax antibody. An immunoreactive score (IRS) was calculated by multiplying the grade of percentage of positive cells by the grade of intensity of Bax immunostaining.
Results: All the studied valves showed positive Bax immunostaining that was predominantly detected in the cytoplasm of interstitial fibroblasts "especially in areas adjacent to calcification" as well as the endothelial cells of the new-capillary sprouts present in the valvular interstitium. A differentiating feature was the positive Bax immunostaining, detected only in the cytoplasm of the valvular surface endothelial cells of rheumatic cases. Also, areas of neovascularization were more abundant in degenerative aortic valves and in the vicinity of calcification of these valves. The IRS was higher in degenerative aortic valve stenosis compared to rheumatic valves.
Conclusions: Our data attest that apoptosis contributes to calcification of stenotic aortic valve cusps. However, the interplay of endothelial cells and fibroblasts apoptosis in the pathogenesis of rheumatic and degenerative aortic stenosis seems to be different. Understanding the role of apoptosis and angiogenesis in the pathogenesis of both rheumatic and degenerative aortic stenosis offers the potential to develop targeted therapeutic regimens. |