Have we found the missing link between inflammation, fibrosis, and calcification in calcific aortic valve disease?. (23rd January 2023) - Martin, Marcy
Graphical Abstract: Graphical Abstract Host responses leading to native heart valve degeneration and valve replacement inflammation. ( A ) Cellular mechanisms of valve degeneration depiction in calcific aortic valve disease (CAVD). First, mechanical or biochemical insults initiate immune cell infiltration in the native valve, which then differentiate into proinflammatory cells (e.g. M1 macrophages). As chronic inflammation persists, resident valvular interstitial cells (VICs) activate into inflammatory myofibrotic–osteogenic (IMO)-VICs, which promote fibrosis and calcification. Sortilin may be a therapeutic target to inhibit fibrocalcification progression. ( B ) Illustration depicting the reducing incidence of chronic inflammation based on valve replacement structural properties. Homografts and bioprostheses suffer from structural degeneration over time, due to tissue processing techniques or intrinsic material properties. 6 Decellularized homografts and xenografts are potential substitutes if decellularization procedures meet clinical standards. Non-degradable polymeric valves have shown enhanced durability and haemodynamic properties over bioprostheses and decellularized xenografts; 18 long-term studies are needed to compare with decellularized homografts. Finally, tissue-engineered heart valves, i.e. bioresorbable polymeric or in vitro grown human tissue-engineered matrices (hTEMs), represent next-generation candidates that have intrinsic properties such as host-driven remodelling and self-repair.