Targeting the endothelial Ca 2+ tool kit to rescue endothelial dysfunction in obesity associated-hypertension

(E-pub Abstract Ahead of Print)

Author(s): Francesco Moccia* , Sharon Negri , Pawan Faris , Roberto Berra-Romani .

Journal Name: Current Medicinal Chemistry


Background: Obesity is a major cardiovascular risk factor which dramatically impairs endothelium-dependent vasodilation and leads to hypertension and vascular damage. The impairment of the vasomotor response to extracellular autacoids, e.g. acetylcholine, mainly depends on the reduced nitric oxide (NO) bioavailability, which hampers vasorelaxation in large conduit arteries. In addition, obesity may affect endothelium-dependent hyperpolarization (EDH), which drives vasorelaxation in small resistance arteries and arterioles. Of note, endothelial Ca 2+ signals drive NO release and trigger EDH.

Methods: A structured search of bibliographic databases was carried out to retrieve the most influential, recent articles on the impairment of vasorelaxation in animal models of obesity, including obese Zucker rats, and on the remodeling of the endothelial Ca 2+ toolkit under conditions that mimic obesity. Furthermore, we searched for articles discussing how dietary manipulation could be exploited to rescue Ca 2+ -dependent vasodilation.

Results: We found evidence that the endothelial Ca 2+ could be severely affected by obese vessels. This rearrangement could contribute to endothelial damage and is likely to be involved in the disruption of vasorelaxant mechanisms. However, several Ca 2+ -permeable channels, including Vanilloid Transient Receptor Potential (TRPV) 1, 3 and 4 could be stimulated by several food components to stimulate vasorelaxation in obese individuals.

Conclusion: The endothelial Ca 2+ toolkit could be targeted to reduce vascular damage and rescue endothelium-dependent vasodilation in obese vessels. This hypothesis remains, however, to be probed on truly obese endothelial cells.

Keywords: endothelial dysfunction, cardiovascular risk factor, endothelium-dependent hyperpolarization , EDH, endothelial dysfunction tool kit

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Article Details

(E-pub Abstract Ahead of Print)
DOI: 10.2174/0929867326666190905142135
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