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 < 0.001). Inhibition of MAPK38 and GSK3β significantly reduced Lp(a)-induced calcification of human aortic valve interstitial cells (p < 0.001). There was abundant presence of Lp(a) and E06 immunoreactivity in diseased human aortic valves. The present study demonstrates a causal effect for Lp(a) in aortic valve calcification and suggests that interfering with the Lp(a)pathway could provide a novel therapeutic approach in the management of this debilitating disease.
Keywords: ALP, alkaline phosphatase; BMP, bone morphogenetic protein; FWHM, full width half maximum; HAVIC, human aortic valve interstitial cell; LDL, low-density lipoprotein; LOX-1, oxidized LDL receptor 1; Lp(a), lipoprotein(a); MAPK, mitogen-activated protein kinase; MGP, matrix Gla protein; OxPL, oxidized phospholipid; Raman spectroscopy; apo(a), apolipoprotein(a); mRNA, messenger ribonucleic acid; oxidized phospholipids; real-time PCR; stenosis.