STIM and Orai proteins: players in sexual differences in hypertension-associated vascular dysfunction?

• Published in: Clinical science (1979) Vol. 118; no. 6; pp. 391 - 396
• Main Authors: Giachini, Fernanda R.C., Webb, R. Clinton, Tostes, Rita C.
• Format: Journal Article
• Language: English
• Published: London Portland Press 15.12.2009
• Subjects: Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Calcium - metabolism; Calcium Channels - metabolism; Cardiology. Vascular system; Cell Communication; Female; General aspects; Humans; Hypertension - etiology; Hypertension - metabolism; Male; Medical sciences; Membrane Proteins - metabolism; Microcirculation; Muscle, Smooth, Vascular - metabolism; Myocytes, Smooth Muscle - metabolism; Neoplasm Proteins - metabolism; ORAI1 Protein; Rats; Sex Characteristics; Stromal Interaction Molecule 1; Human; Hypertension; sex difference; Sex; Cardiovascular disease; Cell cell interaction; Male; stromal interaction molecule (STIM); Protein; Orai; Medicine; Molecules; Dysfunction; Blood vessel; Female; Circulatory system; Stromal cell; Comparative study
• ISSN: 0143-5221; 1470-8736; 1470-8736
• DOI: 10.1042/CS20090449

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 Ca2+ handling or, more specifically, in mechanisms that regulate Ca2+ 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 Ca2+ influx, in conditions of intracellular store depletion, were identified: STIM1 (stromal interaction molecule 1), which works as an intracellular Ca2+ sensor; and Orai1, which is a component of the CRAC (Ca2+ release-activated Ca2+) channels. Together, these proteins reconstitute store-operated Ca2+ 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 Ca2+ 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.