Amyloid and collagen templates in aortic valve calcification

Abstract

Calcific aortic valve disease (CAVD) is a widely prevalent heart disorder in need of pharmacologic interventions. Calcified areas in aortic valves often contain amyloid fibrils that promote calcification in vitro. This Opinion paper suggests that amyloid contributes to CAVD development; amyloid-assisted nucleation can accelerate hydroxyapatite deposition onto collagen matrix. Notably, acidic arrays in amyloid match calcium-calcium spacing in amorphous hydroxyapatite precursor, while oscillating hemodynamic perturbations promote amyloid deposition in the valve. Lipoprotein(a), a genetic risk factor for CAVD, augments calcification via several mechanisms, wherein hydrolysis of oxidized phospholipids by lipoprotein(a)-associated enzymes helps generate orthophosphate, and apolipoprotein(a) blocks plasmin-induced fibril degradation. Current studies of amyloid-calcium-collagen interactions in solution and in fibrillar complexes allow deeper insight into role of amyloid in calcification.