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Calcium signaling in endothelial and vascular smooth muscle cells: sex differences and the influence of estrogens and androgens.

Authors :
Asunción-Alvarez D
Palacios J
Ybañez-Julca RO
Rodriguez-Silva CN
Nwokocha C
Cifuentes F
Greensmith DJ
Source :
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2024 Apr 01; Vol. 326 (4), pp. H950-H970. Date of Electronic Publication: 2024 Feb 09.
Publication Year :
2024

Abstract

Calcium signaling in vascular endothelial cells (ECs) and smooth muscle cells (VSMCs) is essential for the regulation of vascular tone. However, the changes to intracellular Ca <superscript>2+</superscript> concentrations are often influenced by sex differences. Furthermore, a large body of evidence shows that sex hormone imbalance leads to dysregulation of Ca <superscript>2+</superscript> signaling and this is a key factor in the pathogenesis of cardiovascular diseases. In this review, the effects of estrogens and androgens on vascular calcium-handling proteins are discussed, with emphasis on the associated genomic or nongenomic molecular mechanisms. The experimental models from which data were collected were also considered. The review highlights 1 ) in female ECs, transient receptor potential vanilloid 4 (TRPV4) and mitochondrial Ca <superscript>2+</superscript> uniporter (MCU) enhance Ca <superscript>2+</superscript> -dependent nitric oxide (NO) generation. In males, only transient receptor potential canonical 3 (TRPC3) plays a fundamental role in this effect. 2 ) Female VSMCs have lower cytosolic Ca <superscript>2+</superscript> levels than males due to differences in the activity and expression of stromal interaction molecule 1 (STIM1), calcium release-activated calcium modulator 1 (Orai1), calcium voltage-gated channel subunit-α <subscript>1C</subscript> (Ca <subscript>V</subscript> 1.2), Na <superscript>+</superscript> -K <superscript>+</superscript> -2Cl <superscript>-</superscript> symporter (NKCC1), and the Na <superscript>+</superscript> /K <superscript>+</superscript> -ATPase. 3 ) When compared with androgens, the influence of estrogens on Ca <superscript>2+</superscript> homeostasis, vascular tone, and incidence of vascular disease is better documented. 4 ) Many studies use supraphysiological concentrations of sex hormones, which may limit the physiological relevance of outcomes. 5 ) Sex-dependent differences in Ca <superscript>2+</superscript> signaling mean both sexes ought to be included in experimental design.

Details

Language :
English
ISSN :
1522-1539
Volume :
326
Issue :
4
Database :
MEDLINE
Journal :
American journal of physiology. Heart and circulatory physiology
Publication Type :
Academic Journal
Accession number :
38334967
Full Text :
https://doi.org/10.1152/ajpheart.00600.2023