Conflict of interest

None.

and epithelial function. To respond to FSS, a functional primary cilium requires the constitutive proteins, PKD1, PKD2 and polaris. The primary cilium is functional under normal FSS and activates the Ca2+ and NO signaling cascade; nevertheless, it becomes dysfunctional after prolonged exposure to high FSS analogous to a hypertensive situation present in any kind of biological fluid. Respectively, growing evidence implicates the primary cilium and the disruption of its function in many diseases such as hypertension, atherosclerotic lesions and acute

In this regards, we have summarized evidences implicating that polycystic kidney disease, a pathology characterized by lack of PKD1 and/or PKD2 expression, leads to impaired vascular endothelial FSS sensing. Even when the primary organ affected by the disease is the kidney, the endothelial dysfunction is a common extra renal symptom observed in polycystic kidney disease. Those patients exhibit an impairment of endothelium-dependent relaxation and a

Contrary to its physiological role in sensing FSS, it has also been described that primary cilium is related to plaque formation, since this organelle was present in the endothelial cells of human aortic fatty dots and streaks. Indeed, primary cilium has been shown to be located at the atherosclerotic predilection sites, where flow is disturbed and around atherosclerotic lesions in the aortic arch in wild-type mice and apolipoprotein E-deficient mice, respectively [31]. In addition, primary cilia have been involved in endothelial activation and dysfunction present in atherosclerosis. Despite relevance of these evidences, it is highlighted in this review that more studies are required to better understand the role of endothelial primary cilium in

We also presented examples of regulatory signals that control NO bioavailability or might participate as modulators of primary cilium. For instance, ROS can modulate cilia length and deciliation process in tubular kidney cells. Whether these effects could be extrapolated to

Finally, we presented the interconnected coreceptors VEGF and VEGFRs, neuropilins, ATP, adenosine and purinergic receptors. All have been suggested to be involved in FSS sensing and/ or colocalization in the primary cilium. To this respect, we can provide more questions than answers. NRP1, a VEGFR2 receptor, localizes to the primary cilium but its physiological relevance is still unknown. On the other hand, ATP and adenosine are involved in sensing FSS, in a primary cilium-independent manner. Moreover, information regarding whether or not

In conclusion, these data emphasize the role of the primary cilium present in endothelial cells as a microsensory organelle transducing FSS. Impairment in the ciliogenesis, cilia length and intracellular pathways can be involved in cardiovascular diseases. The participation of ROS, VEGF and purinergic signaling pathways is being described, but more research is required to elucidate their participation in the primary cilium-mediated sensing of FSS in normal and pathological conditions, such as hypertension, atherosclerosis or polycystic kidney disease.

purinergic signaling can be associated to the primary cilia function is missing.

decrease of primary cilia-dependent NO production leading to hypertension.

normal and pathological conditions, such as atherosclerosis.

endothelial cells is worth of more investigation.

and chronic kidney disease.

102 Endothelial Dysfunction - Old Concepts and New Challenges
