Potential drug targets for calcific aortic valve disease

Abstract

Calcific aortic valve disease (CAVD) seems to be distinct from vascular calcification in terms of both disease mechanisms and progression, although some risk factors are shared Valve-specific drug targets are likely to be required to prevent or treat CAVD, given that drug strategies for vascular disease have not proven successful when applied to CAVD Ubiquitous targeting of the cytokines thought to lead to valve disease is not likely to be feasible or beneficial, because they are required for wound healing elsewhere in the body Targeting specific combinations of G-protein-coupled receptors might simultaneously prevent myofibroblast activation and collagen accumulation, which are thought to be two of the main initiators of, and contributors to, CAVD Functional blocking of cadherin-11 might be an effective target to prevent mechanotransduction between valve cells that is thought to exacerbate cytokine signalling and synergistically lead to calcification Lipid lowering might be an effective strategy for CAVD treatment; however, a targeted approach centred on lowering the lipoprotein(a) level and increasing the HDL-cholesterol level might be required