Role of Lipoprotein(a) in Aortic Valve Calcification: Inflammatory and Oxidative Mechanisms Involved

Lipoprotein(a) [Lp(a)] is a predominantly genetic risk factor for atherosclerotic cardiovascular disease and calcified aortic valve disease (CAVD). In addition to its epidemiological and genetic association with aortic stenosis, Lp(a) transports oxidized phospholipids, lysophosphatidylcholine, and autotaxin, components capable of promoting inflammation, oxidative stress, and valvular fibrocalcifying remodeling. This review synthesizes the molecular, cellular, and clinical evidence linking Lp(a) to CAVD progression. Retention of Lp(a) and other apolipoprotein B-containing lipoproteins in the valvular matrix promotes endothelial activation, monocyte and macrophage recruitment, and the release of proinflammatory mediators. Oxidized phospholipids and the autotaxin-lysophosphatidic acid axis activate redox-dependent pathways and promote the transition of valvular interstitial cells to myofibroblastic and osteogenic phenotypes. These processes converge in alterations in cholesterol metabolism, the release of procalcifying extracellular vesicles, and hydroxyapatite nucleation. Genetic and imaging evidence support an association between elevated Lp(a), microcalcifying activity, and accelerated hemodynamic progression. Although anti-Lp(a) therapies substantially reduce plasma Lp(a) concentrations, their effect on valvular outcomes has not yet been demonstrated.