ReviewMolecular and cellular mechanisms of aortic stenosis
Section snippets
Calcification and aortic stenosis
Histologically, the aortic valve consists of three principal layers, the ventricularis at the inflow surface containing collagen and elastin, the spongiosa in the center composed of glycosaminoglycans and the fibrosa at the outflow surface containing densely packed collagen fibers [3]. The outer surface of the valvular leaflets is lined by endothelial cells that cover interstitial mesenchymal cells located throughout the leaflets [4]. Normally, aortic valves are avascular and their oxygen
Non-rheumatic aortic stenosis and atherosclerosis
Histopathologic evidence suggests that early lesions in aortic valves are not just a disease process secondary to aging, but an active cellular process that follows the classical “response to injury hypothesis” similar to the situation in atherosclerosis [19].
The growing body of literature suggests that hypercholesterolemia may play a role in aortic valve calcification. Dr. Rajamannan's laboratory has studied the hypothesis whether experimental hypercholesterolemia may play a key role in the
Lipid lowering and progression of aortic valve stenosis
The effects of statin treatment on aortic stenosis has gained importance recently based on the data of several trials [6], [38], [39], [40], [41]. In one of these trials, the use of a statin was inversely associated with the progression of aortic stenosis [38]. Regarding statins and their association with AS, there is evidence that statin therapy is associated with markedly lower hemodynamic progression of AS. Furthermore, Rosenhek et al. [6] have demonstrated that this effect is independent of
Angiogenesis, growth factors and non-rheumatic aortic stenosis
Angiogenesis is defined as the outgrowth of new capillaries from pre-existing capillaries and is regulated by a balance between angiogenic activators such as VEGF, FGF-2 and PDGF, and angiogenic inhibitors [46]. It has been reported that the activation of angiogenesis in aortic valves occurs in a close association with valvular stenosis, particularly with calcified aortic valve stenosis [47]. Calachour et al. [47] have demonstrated that the formation of angiogenic sprouts from stenotic valves
Extracellular matrix remodeling in aortic stenosis
A number of ECM proteins normally found in bone, including osteocalcin, osteopontin, osteonectin, bone morphogenetic protein, matrix metalloproteinase-2 (MMP-2), and MMP-9, are present in cardiovascular calcifications, including calcified valves, but in general are not found in normal cardiovascular tissue [15], [74], [75], [76], [77], [78], [79]. Matrix metalloproteinases are most commonly evaluated extracellular matrix proteins in the pathogenesis of calcific aortic stenosis. Those are a
Infection, inflammation and aortic stenosis
The first findings indicating that there might be an association of infection and non-rheumatic calcific aortic stenosis was reported in 1973 [102]. Shor et al. [103] was the first to morphologically demonstrate C. pneumoniae within human arteries affected by atherosclerosis, initially by electron microscopy and subsequently confirmed by immunofluorescence. So far the evidence for C. pneumoniae as a potential causative agent for CAD have been reported, based on the findings of numerous
Conclusions
In conclusion there are several pathophysiologic mechanisms which are supposed to be responsible for the occurrence of non-rheumatic calcific aortic stenosis. Although there are similarities with the process of atherogenesis as well as with some risk factors, not all the patients with coronary artery disease or atherosclerosis develop calcific aortic stenosis. So there must be some differentiating process. Still, the impact of cardiovascular risk factors on calcific aortic stenosis is not clear
Acknowledgement
The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [127].
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