A Not-So-Little Role for Lipoprotein(a) in the Development of Calcific Aortic Valve Disease.

Abstract

Alterations in lipid metabolism and inflammatory processes are well established as potential risk factors in the development and progression of cardiovascular disease.1 However, with complications ranging from valve dysfunction to arrhythmia to myocardial infarction and stroke, the underlying mechanisms may be as varied as cardiovascular disease itself. On the other hand, the reoccurrence of common molecular and cellular pathways identified in the collective body of cardiovascular research could suggest shared initiators or mechanistic nodes between seemingly divergent processes, including lipid metabolism and inflammation. One area where this may hold true is cardiovascular calcification, in which dysregulated mineral metabolism in cardiovascular tissues leads to increased morbidity and mortality. Article see p 677 Calcification of soft tissues results from the deposition of calcium, largely in the form of hydroxyapatite, in the vascular wall or valve leaflets. Previously thought to be a passive degenerative process, it has become increasingly apparent that cardiovascular calcification is an active process initiated by many triggers. Recent studies have demonstrated variation in the LPA gene, which determines the plasma concentration of lipoprotein(a) [Lp(a); pronounced “L P little a”] to be associated with calcific aortic valve disease (CAVD).2,3 Lp(a) consists of a low-density lipoprotein (LDL)–like particle in which apolipoprotein(a) is covalently bound to apolipoprotein B. Additionally, Lp(a) is a genetic risk factor for atherosclerotic events.4 As in atherosclerosis, calcifications in CAVD localize to areas with lipoprotein accumulation and inflammatory cell infiltration, suggesting a shared disease process.5 However, some noticeable differences exist, including increased mechanical stresses and calcification-involved valve obstruction in CAVD as opposed to microcalcifications leading atherosclerosis plaque rupture.6 In this issue of Circulation , Bouchareb et al7 propose a highly plausible mechanistic pathway through which Lp(a) and valve interstitial cell (VIC)–derived autotaxin may induce valve calcification by regulating inflammation-induced bone …