title: Modulation of Local and Systemic Heterocellular Communication by Mechanical Forces: A Role of Endothelial Nitric Oxide Synthase.
abstract: In this review, we discuss the role of nitric oxide (NO) as a key physiological mechanotransducer modulating both local and systemic heterocellular communication and contributing to the integrated (patho)physiology of the cardiovascular system. A deeper understanding of mechanotransduction-mediated local and systemic nodes controlling heterocellular communication between the endothelium, blood cells, and other cell types (e.g., cardiomyocytes) may suggest novel therapeutic strategies for endothelial dysfunction and cardiovascular disease. Recent Advances: Mechanical forces acting on mechanoreceptors on endothelial cells activate the endothelial NO synthase (eNOS) to produce NO. NO participates in (i) abluminal heterocellular communication, inducing vasorelaxation, and thereby regulating vascular tone and blood pressure; (ii) luminal heterocellular communication, inhibiting platelet aggregation, and controlling hemostasis; and (iii) systemic heterocellular communication, contributing to adaptive physiological processes in response to exercise and remote ischemic preconditioning. Interestingly, shear-induced eNOS-dependent activation of vascular heterocellular communication constitutes the molecular basis of all methods applied in the clinical routine for evaluation of endothelial function. Critical Issues and Future Directions: The integrated physiology of heterocellular communication is still not fully understood. Dedicated experimental models are needed to analyze messengers and mechanisms underpinning heterocellular communication in response to physical forces in the cardiovascular system (and elsewhere). Antioxid. Redox Signal. 26, 917-935.
authors.affiliation: Cardiovascular Research Laboratory, Division of Cardiology, Pneumology and Angiology, Medical Faculty, Heinrich Heine University of Düsseldorf , Düsseldorf, Germany .
authors.forename: Ralf
authors.initials: R
authors.lastname: Erkens
authors.affiliation: Cardiovascular Research Laboratory, Division of Cardiology, Pneumology and Angiology, Medical Faculty, Heinrich Heine University of Düsseldorf , Düsseldorf, Germany .
authors.forename: Tatsiana
authors.initials: T
authors.lastname: Suvorava
authors.affiliation: Cardiovascular Research Laboratory, Division of Cardiology, Pneumology and Angiology, Medical Faculty, Heinrich Heine University of Düsseldorf , Düsseldorf, Germany .
authors.forename: Christian M
authors.initials: CM
authors.lastname: Kramer
authors.affiliation: Cardiovascular Research Laboratory, Division of Cardiology, Pneumology and Angiology, Medical Faculty, Heinrich Heine University of Düsseldorf , Düsseldorf, Germany .
authors.forename: Lukas D
authors.initials: LD
authors.lastname: Diederich
authors.affiliation: Cardiovascular Research Laboratory, Division of Cardiology, Pneumology and Angiology, Medical Faculty, Heinrich Heine University of Düsseldorf , Düsseldorf, Germany .
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
authors.affiliation: Cardiovascular Research Laboratory, Division of Cardiology, Pneumology and Angiology, Medical Faculty, Heinrich Heine University of Düsseldorf , Düsseldorf, Germany .
authors.forename: Miriam M
authors.initials: MM
authors.lastname: Cortese-Krott
mesh_terms: D000818:Animals; D002450:Cell Communication; D042783:Endothelial Cells / Q000166:cytology* / Q000201:enzymology; D006801:Humans; D040542:Mechanotransduction, Cellular; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D013314:Stress, Mechanical
chemical_list: D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III
keywords: endothelial dysfunction; mechanobiology; nitric oxide; red blood cells; red cell eNOS; shear stress