10. Concluding remarks

Phenotypic cell alterations resulting from flow-induced mechanical strains and their implication in diseases are a growing field of research in many cell types such as vascular endothelial, smooth muscle, kidney epithelial cells and chondrocytes.

In the chapter, we presented the role of the primary cilium as one of the multiple physiological mechanosensors for FSS in endothelial and renal cells, where it regulates vascular homeostasis 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 and chronic kidney disease.

Acknowledgements

Conflict of interest

Source of funding

166709 3/R and GI 171709/VC.

Financial disclosure

Abbreviations

None.

None.

discussion of the ideas presented in this manuscript.

eNOS Endothelial nitric oxide synthase

FGF Fibroblast growth factor

FSS Fluid shear stress

ERK Extracellular signal-regulated Kinase

Gli Glioblastoma transcription factors

HUVECs Human umbilical vein endothelial cells

MMDD1 Immortalized macula densa cell line

HH Hedgehog signaling pathway

HGF Hepatocyte growth factor

We would like to thank the research staff of the Vascular Physiology Laboratory; the Group of Investigation in Tumor Angiogenesis (GIANT) from the Universidad del Bío-Bío; Group of Research and Innovation in Vascular Health (GRIVAS Health) group for the outstanding

Sensing Fluid-Shear Stress in the Endothelial System with a Special Emphasis on the Primary Cilium

http://dx.doi.org/10.5772/intechopen.73134

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This study was supported by Fondecyt Regular 1140586; Fondequip EQM140104; DIUBB

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

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 normal and pathological conditions, such as atherosclerosis.

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 endothelial cells is worth of more investigation.

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

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.
