Abstract 14956: Lr11 Gene Deficiency Prevents Hypoxia-induced Pulmonary Hypertension and Vascular Remodeling in Mice
INTRODUCTION: LR11 (also called SorLA or SORL1), is a low-density lipoprotein (LDL)-receptor that is expressed in intimal smooth muscle cells during the development of atherosclerosis. Pulmonary arterial hypertension is characterized by excessive proliferation of the pulmonary arterial SMCs (PASMCs). However it has not explored that LR11 gene deletion can regulate smooth muscle cell proliferation in pulmonary hypertension. In this study, we hypothesized that LR11 could play a role in the proliferation of PASMCs.
OBJECTIVE: The aim of this study is to investigate the possible effect of LR11 gene deletion is suppressing SMCs proliferation in pulmonary hypertension and vascular remodeling under hypoxia- induced animal models.
METHODOLOGY & RESULTS: C57/BL6 (WT) and LR11-/- mice were exposed to either normoxia or hypoxia for 3 weeks. Three weeks after 10% hypoxia exposure, right ventricular systolic pressure (RVSP) of LR11-/- mice was significantly lower compare to WT mice (28±2.3mmHg vs 33±2.0mmHg;p<0.001). The ratio of right ventricle weight/(left ventricle + septum) weight in LR11-/- mice was significantly lower compared to WT mice (31.2±2.2% vs 36.3±2.4%;p <0.05). Medial wall thickness of pulmonary arterioles percentage was significant reduced in LR11-/- mice as compared to WT mice (3.6±0.5% vs 5.7±0.4%;p<0.001). Western blot analysis showed LR11 and HIF-1α expression up-regulated in wild-type mice under hypoxia. HIF-1α expression up-regulated in LR11-/- mice under hypoxia however LR11 expression was not observed. We measured serum soluble (sLR11) levels using ELISA kit. For 3 weeks under hypoxia, sLR11 was increased in WT mice compared to WT mice under normoxia. (4.6±0.7μg/ml vs 6.5±1.0 μg/ml;P<0.05).
CONCLUSION: Deletion of LR11 gene prevented the development of hypoxia-induced pulmonary hypertension and vascular remodeling in mice and revealed a novel regulation pathway associated with LR11 signaling.
Author Disclosures: L. Jiang: None. H. Konishi: None. M. Jiang: None. H. Bujo: None. H. Daida: None.
- © 2014 by American Heart Association, Inc.