STIM and Orai proteins: players in sexual differences in hypertension-associated vascular dysfunction?
Sex-associated differences in hypertension have been observed repeatedly in epidemiological studies; however, the mechanisms conferring vascular protection to females are not totally elucidated. Sex-related differences in intracellular Ca(2+) handling or, more specifically, in mechanisms that regulate Ca(2+) entry into vascular smooth muscle cells have been identified as players in sex-related differences in hypertension-associated vascular dysfunction. Recently, new signalling components that regulate Ca(2+) influx, in conditions of intracellular store depletion, were identified: STIM1 (stromal interaction molecule 1), which works as an intracellular Ca(2+) sensor; and Orai1, which is a component of the CRAC (Ca(2+) release-activated Ca(2+)) channels. Together, these proteins reconstitute store-operated Ca(2+) channel function. Disturbances in STIM1/Orai1 signalling have been implicated in pathophysiological conditions, including hypertension. In the present article, we analyse evidence for sex-related differences in Ca(2+) handling and propose a new hypothesis where sex-related differences in STIM/Orai signalling may contribute to hypertension-associated vascular differences between male and female subjects.
Giachini
Fernanda R C
FR
Department of Physiology, Medical College of Georgia, Augusta, GA 30912-3000, U.S.A. fgiachini@mcg.edu
Webb
R Clinton
RC
Tostes
Rita C
RC
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002450:Cell Communication; D005260:Female; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008833:Microcirculation; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D000071740:ORAI1 Protein; D051381:Rats; D012727:Sex Characteristics; D000071737:Stromal Interaction Molecule 1
D015220:Calcium Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D002118:Calcium