Visual Abstract
Highlights • Lp(a) significantly increased alkaline phosphatase activity, phosphate and calcium content, and matrix vesicle formation and induced apoptosis and calcification of normal human aortic valve interstitial cells. • The type of minerals induced by Lp(a) resembles that seen in calcified human aortic valves as shown by Raman spectroscopy. • Lp(a)-induced calcification of human aortic valve interstitial cells is mediated by activation of MAPK38, GSK3β, and Wnt signaling. • Inhibition of GSK3β and MAPK38 significantly reduced lipoprotein(a)-induced aortic valve interstitial cell calcification. • Lp(a)is abundant in calcified aortic valves, and lipoprotein(a) immunoreactivity colocalized with that of oxidized phospholipids.
Summary Lipoprotein(a), or Lp(a), significantly increased alkaline phosphatase activity, release of phosphate, calcium deposition, hydroxyapatite, cell apoptosis, matrix vesicle formation, and phosphorylation of signal transduction proteins; increased expression of chondro-osteogenic mediators; and decreased SOX9 and matrix Gla protein (p