Abstract
Primary cilia are microtubule-based organelles found in most mammalian cell types. Cilia act as sensory organelles that transmit extracellular clues into intracellular signals for molecular and cellular responses. Biochemical and molecular defects in primary cilia are associated with a wide range of diseases, termed ciliopathies, with phenotypes ranging from polycystic kidney disease, liver disorders, mental retardation, and obesity to cardiovascular diseases. Primary cilia in vascular endothelia protrude into the lumen of blood vessels and function as molecular switches for calcium (Ca2+) and nitric oxide (NO) signaling. As mechanosensory organelles, endothelial cilia are involved in blood flow sensing. Dysfunction in endothelial cilia contributes to aberrant fluid-sensing and thus results in vascular disorders, including hypertension, aneurysm, and atherosclerosis. This review focuses on the most recent findings on the roles of endothelial primary cilia within vascular biology and alludes to the possibility of primary cilium as a therapeutic target for cardiovascular disorders.
Highlights
Cilia have been studied for their motile functions of lung epithelium, sperm cells, as well as in other organisms [1]
Activation of primary cilia by blood flow leads to the activation of PC1 and PC2 resulting in an intracellular Ca2+ signaling network involving calmodulin (CaM), calcium-dependent protein kinase (PKC), serine-threonine kinase/protein kinase B (Akt/PKB) and endothelial nitric oxide synthase
When individuals are perfused with 0.25–0.5 μg/kg/min of dopamine, the results indicated an upward trend in flow-mediated dilation in autosomal dominant polycystic kidney disease (ADPKD) patients and reported a statistically significant decrease in hypertension [145]
Summary
Cilia have been studied for their motile functions of lung epithelium, sperm cells, as well as in other organisms (such as algae) [1]. These motile cilia, in most cases, have 9 + 2 microtubule structural arrangement. Because primary cilia act as sensory organelles by which cells sense and transduce extracellular signals [4], any defects in primary cilia function could potentially cause several diseases which are collectively known as ‘ciliopathies’ (Table 1). It is important to have a clear understanding about ciliary structure and functional ciliary proteins to investigate how cilia dysfunction can contribute to vascular disorders of hypertension, aneurysm and atherosclerosis
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