lb-100 and Calcinosis

To investigate the role of PP2A in calcified aortic valve disease (CAVD).. The expressions of PP2A subunits were detected by real-time polymerase chain reaction (RT-PCR) and western blot in aortic valves from patients with CAVD and normal controls, the activities of PP2A were analyzed by commercial assay kit at the same time. Aortic valve calcification of mice was evaluated through histological and echocardiographic analysis. ApoE. PP2A activity was decreased both in calcified aortic valves and human VICs under osteogenic induction. The PP2A inhibitor LB100 aggravated the aortic valve calcification of mice. Furthermore, PPP2CA overexpression inhibited osteogenic differentiation of VICs, whereas PPP2CA knockdown promoted the process. Further study revealed that the ERK/p38 MAPKs signaling pathways mediated the osteogenic differentiation of VICs induced by PP2A inactivation.. This study demonstrated that PP2A plays an important role in CAVD pathophysiology, PP2A activation may provide a novel strategy for the pharmacological treatment of CAVD.

Topics: Animals; Aortic Valve; Aortic Valve Stenosis; Apolipoproteins E; Calcinosis; Cell Differentiation; Gene Knockdown Techniques; Humans; Male; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Mice, Knockout; Osteogenesis; p38 Mitogen-Activated Protein Kinases; Piperazines; Protein Phosphatase 2; Real-Time Polymerase Chain Reaction