title: Gasotransmitters in Vascular Complications of Diabetes.
abstract: In the past decades three gaseous signaling molecules-so-called gasotransmitters-have been identified: nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S). These gasotransmitters are endogenously produced by different enzymes in various cell types and play an important role in physiology and disease. Despite their specific functions, all gasotransmitters share the capacity to reduce oxidative stress, induce angiogenesis, and promote vasorelaxation. In patients with diabetes, a lower bioavailability of the different gasotransmitters is observed when compared with healthy individuals. As yet, it is unknown whether this reduction precedes or results from diabetes. The increased risk for vascular disease in patients with diabetes, in combination with the extensive clinical, financial, and societal burden, calls for action to either prevent or improve the treatment of vascular complications. In this Perspective, we present a concise overview of the current data on the bioavailability of gasotransmitters in diabetes and their potential role in the development and progression of diabetes-associated microvascular (retinopathy, neuropathy, and nephropathy) and macrovascular (cerebrovascular, coronary artery, and peripheral arterial diseases) complications. Gasotransmitters appear to have both inhibitory and stimulatory effects in the course of vascular disease development. This Perspective concludes with a discussion on gasotransmitter-based interventions as a therapeutic option.
authors.affiliation: Department of Pathology and Medical Biology, Division of Pathology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Joost C
authors.initials: JC
authors.lastname: van den Born
authors.affiliation: 5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hammes
authors.affiliation: Department of Neurophysiology, Centre for Biomedicine and Medical Technology Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Greffrath
authors.affiliation: Department of Pathology and Medical Biology, Division of Pathology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
authors.affiliation: Department of Pathology and Medical Biology, Division of Pathology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands j.l.hillebrands@umcg.nl.
authors.forename: Jan-Luuk
authors.initials: JL
authors.lastname: Hillebrands
mesh_terms: D001682:Biological Availability; D002248:Carbon Monoxide / Q000502:physiology; D003920:Diabetes Mellitus / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000209:etiology / Q000503:physiopathology*; D064426:Gasotransmitters / Q000502:physiology*; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000209:etiology; D009569:Nitric Oxide / Q000502:physiology; D018384:Oxidative Stress; D014664:Vasodilation
chemical_list: D064426:Gasotransmitters; D009569:Nitric Oxide; D002248:Carbon Monoxide; D006862:Hydrogen Sulfide