Lipoprotein(a) Induces Human Aortic Valve Interstitial Cell Calcification
oleh: Bin Yu, PhD, Anouar Hafiane, PhD, George Thanassoulis, MD, Leah Ott, BS, Nial Filwood, MD, Marta Cerruti, PhD, Ophélie Gourgas, MS, Dominique Shum-Tim, MD, Hamood Al Kindi, MD, Benoit de Varennes, MD, Alawi Alsheikh-Ali, MD, PhD, Jacques Genest, MD, Adel Schwertani, DM, PhD
| Format: | Article |
|---|---|
| Diterbitkan: | Elsevier 2017-08-01 |
Deskripsi
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.