AWARD NUMBER: W81XWH-14-1-0464 TITLE: The Roles of Primary Cilia in Cardiovascular System PRINCIPAL INVESTIGATOR:

Primary cilia are sensory organelles that extend from the cell surface and senseextracellular signals. Endothelial primary cilia protruding from the inner surface of blood vessel wallssense changes in blood flow and convert this mechanosensation into an intracellular biochemical/molecular signal, which triggers a cellular response. Primary endothelial cilia dysfunction maycontribute to the impairment of this response and thus be directly implicated in the development ofvascular abnormalities such as hypertension and aneurysms. Using both in vitro techniques as well as in vivo animalmodels, we and others have investigated fluid flow mechanosensory functions of endothelial cilia in cultured cells, animalmodels and autosomal dominant polycystic kidney disease (ADPKD) patients. More in-depth studies directed atidentification of the mechanisms of fluid flow sensing will further enhance our knowledge of cilia-dependent vascularpathology. Although the current treatments aimed at treating the cardiovascular symptoms in ADPKD patients successfullyslowed the progression of cyst growth, there is growing evidence which suggests that drugs which interfere with primarycilia function or structure could reduce cardiovascular complications in ADPKD. This review is to summarize the mostrecent studies on primary endothelial cilia function in the vascular system and to present primary cilia as a noveltherapeutic target for vascular hypertension.