Abstract 17600: Lipid Phosphate Phosphatase 3 Negatively Regulates Smooth Muscle Cell Phenotypic Modulation and Limits Neotimal Hyperplasia

Rationale: A common SNP in PPAP2b associates with risk of coronary artery disease (CAD). PPAP2b encodes the lipid phosphate phosphatases (LPP) 3 that degrades and thereby may attenuate lysophosphatidic acid (LPA) responsiveness of cells. However, a pathophysiologic role for LPP3 in vascular cells remains to be established. Objective: To determine the role and mechanisms by which LPP3 regulates vascular SMC responses. Methods and Results: Robust expression of LPP3 occurs in experimental atherosclerosis and following arterial injury, where SMC serve as the predominant source. Mice with selective inactivation of LPP3 in SMC display an exaggerated neointimal response to carotid ligation injury. Gain- and loss-of-function approaches establish that a major function of LPP3 in isolated SMC cells is to attenuate proliferation, ERK activity, Rho activation and migration in response to serum and LPA. These effects are, at least partially, a consequence of LPP3-catalyzed LPA hydrolysis. We did not observe systemic e...