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

摘要

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: STIM I (stromal interaction molecule I), which works as an intracellular Ca~(2+) sensor; and Orai I, 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 STIM I/Orai I 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.