Cellular Mechanisms of Valvular Thickening in Early and Intermediate Calcific Aortic Valve Disease

Background: Calcific aortic valve disease is common in an aging population. It is an active atheroinflammatory process that has an initial pathophysiology and similar risk factors as atherosclerosis. However, the ultimate disease phenotypes are markedly different. While coronary heart disease results in rupture-prone plaques, calcific aortic valve disease leads to heavily calcified and ossified valves. Both are initiated by the retention of low-density lipoprotein particles in the subendothelial matrix leading to sterile inflammation. In calcific aortic valve disease, the process towards calcification and ossification is preceded by valvular thickening, which can cause the first clinical symptoms. This is attributable to the accumulation of lipids, inflammatory cells and subsequently disturbances in the valvular extracellular matrix. Fibrosis is also increased but the innermost extracellular matrix layer is simultaneously loosened. Ultimately, the pathological changes in the valve cause massive calcification and bone formation - the main reasons for the loss of valvular function and the subsequent myocardial pathology. Conclusion: Calcification may be irreversible, and no drug treatments have been found to be effective, thus it is imperative to emphasize lifestyle prevention of the disease. Here we review the mechanisms underpinning the early stages of the disease.