The Roles of Primary Cilia in Cardiovascular Diseases

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.

Collateral Vessels Have Unique Endothelial and Smooth Muscle Cell Phenotypes

“…Based on studies in other cell types including bovine aorta and human umbilical vein ECs [32,33,34], these are invaginations of the plasmalemma that abut the ciliary membrane to form the ciliary pocket, which houses the proximal end of luminal primary cilia (PrC) that were removed by shearing forces (“depilated/de-ciliated”) during infusion of Batson’s #17. The Batson’s-filled ciliary pockets (i.e., PrC) were commonly located near the nucleus, in accordance with the base of the cilium being associated with the basal body [34,35,36,37,38,39,40]. Distal arterioles also have cilia (Figure S1).…”

“…Collaterals had increased expression of Pycard, Ki67, Pdgfb, Angpt2, Dll4, Ephrinb2 , and eNOS, whereas 16 other genes were not significantly different. Of note, expression of the EC shear stress-sensitive transcription factors Klf2 and Klf4, which promote anti-proliferative, -inflammatory, and -angiogenic processes, upregulate eNOS, and are sharply downregulated at vascular sites of low and disturbed shear stress [35,36,37,44,45], were, in contrast, not downregulated in collaterals compared to DMAs with laminar high-velocity flow.…”

Primary Ciliary Signaling in the Skin—Contribution to Wound Healing and Scarring

“…PC are also involved in endothelial cell inflammatory signaling, as their loss promotes vascular inflammation (Dinsmore and Reiter, 2016), and their length is controlled by cytokine stimuli, as mentioned above (Dummer et al, 2018). Defects in endothelial PC cause disorders of blood fluid-induced responses and result in vascular dysfunctions, such as hypertension, aneurysm, and atherosclerosis (Pala et al, 2018).…”

Pathogenesis of atherosclerosis in the tunica intima, media, and adventitia of coronary arteries: An updated review

“…These regions are predominantly found at the branches and curvatures of large vessels. The blood flow in branches and curvatures is disturbed with nonuniform and irregular low wall shear stress, which is detected by endothelial primary cilia sensitive to the shear stress [32,33]. This disturbed flow and low shear stress modulate the expression and structure of permeability-related intercellular junctional proteins in endothelial cells [34].…”