Abstract
The vascular endothelium consists of a single layer of squamous endothelial cells (ECs) lining the inner surface of blood vessels. Nowadays, it is no longer considered as a simple barrier between the blood and vessel wall, but a central hub to control blood flow homeostasis and fulfill tissue metabolic demands by furnishing oxygen and nutrients. The endothelium regulates the proper functioning of vessels and microcirculation, in terms of tone control, blood fluidity, and fine tuning of inflammatory and redox reactions within the vessel wall and in surrounding tissues. This multiplicity of effects is due to the ability of ECs to produce, process, and release key modulators. Among these, gasotransmitters such as nitric oxide (NO) and hydrogen sulfide (H2S) are very active molecules constitutively produced by endotheliocytes for the maintenance and control of vascular physiological functions, while their impairment is responsible for endothelial dysfunction and cardiovascular disorders such as hypertension, atherosclerosis, and impaired wound healing and vascularization due to diabetes, infections, and ischemia. Upregulation of H2S producing enzymes and administration of H2S donors can be considered as innovative therapeutic approaches to improve EC biology and function, to revert endothelial dysfunction or to prevent cardiovascular disease progression. This review will focus on the beneficial autocrine/paracrine properties of H2S on ECs and the state of the art on H2S potentiating drugs and tools.
Highlights
Accumulating evidence indicates that epigenetic pathways play an important role in eNOS gene regulation [19]. These findings suggest the importance to deeply understand the epigenetic mechanisms involved in the regulation of vascular functions both in physiology and in pathological conditions
hydrogen sulfide (H2 S) acts at several levels on the mechanisms responsible for angiogenesis, including the control of vascular endothelial growth factor (VEGF) expression, through upregulation of the transcription factor hypoxia inducible factor-1α (HIF-1α) or direct modulation of the PI3K and Akt pathways in endothelial cells (ECs) [41,72,73]
Most of its activities are due to autocrine/paracrine actions by ECs, with a fine control of its plasma concentrations
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The vascular endothelium is the tissue that lines the inside of the circulatory system (blood vessels, lymphatic vessels and heart). The endothelial lining represents a wide area for the exchanges between blood and tissues (about 350 m2 in humans) [3]. Electron microscopy observations reveal the continuous nature of arterial endothelium, characterized by tight junctions among adjacent cells in order to limit macromolecule exchange, and by a complex micro-vesicular system. In spite of its apparent morphological lack of complexity, the endothelium is characterized by heterogeneity, with differences in permeability, reactivity, and biosynthesis in relation to the type of vascular district and organ considered [1,2,3]
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