Abstract 108: Role of Primary Endothelial Cilia in Hypertension

Abstract

Primary cilia are mechanosensory organelles that are projected into the lumen of blood vessels. It has been demonstrated that vascular endothelia require primary cilia to sense and transmit external mechanical stimuli into internal biochemical reactions. One of these reactions includes the biosynthesis and release of nitric oxide, which is one of the most potent endogenous vasodilators. This idea has only been investigated in cultured endothelial cells in vitro . Based on this finding, however, a very bold hypothesis is formed to test that abnormal cilia function results in vascular hypertension. Our laboratory has recently generated and obtained several conditional mouse models to specifically study the function and structure of primary cilia in vascular endothelia. These models include 1) mice without cilia function ( Pkd1 or Pkd2 ); 2) mice without cilia structure ( Tg737 or Kif3a ). Our data indicate that mice with abnormal cilia function ( Pkd1 ) or structure ( Tg737 ) show significantly higher systolic (150±19 for Pdgfbcre:Pkd1 flox/flox and 147±10 for Tie2Cre:Tg737 flox/flox vs. 128±9 for wild-type) and diastolic (120±21 for Pdgfbcre:Pkd1 flox/flox and 120±11 for Tie2Cre:Tg737 flox/flox vs. 102±7 for wild-type) blood pressure than the corresponding wild-type mice. Because there is a positive and continuous correlation between blood pressure and cardiovascular diseases, satellite hypotheses are developed to look at the pathophysiological roles of endothelial cilia in cardiac functions and focal vascular diseases in vivo . Our data clearly point towards deteriorating phenotypes in the cardiac muscle, including cardiac fibrosis due to an increased cardiac workload. As a result, a heart-to-body weight ratio was significantly increased by 17 weeks old (0.008 PdgfbCre;Pkd1 f/f vs. 0.006 Pkd1 f/f ).The present study will very likely provide new insights for hypertension and offer advanced scientific understanding of vascular endothelial cilia in other cardiovascular diseases.