Rationale: Orai1 and the associated calcium release-activated calcium (CRAC) channel were discovered in the immune system. Existence also in endothelial cells has been suggested, but the relevance to endothelial biology is mostly unknown.Objective: The aim of this study was to investigate the relevance of Orai1 and CRAC channels to vascular endothelial growth factor (VEGF) and endothelial tube formation. Methods and Results:

.-Glucocorticoid overexposure in utero may underlie the association between low birth weight and subsequent development of common cardiovascular and metabolic pathologies. Previously, we have shown that prenatal dexamethasone (DEX) exposure in rat reduces birth weight and programs the hypothalamic-pituitary axis and fasting and postprandial hyperglycemia in adult males and hypertension in adult males and females. This study aimed to determine 1) whether there were gender differences in prenatal DEX-programmed offspring, and 2) whether the renin-angiotensin system (RAS) plays a role in the programming of hypertension. Rats exposed to DEX in utero (100 g ⅐ kg Ϫ1 ⅐ day Ϫ1 from embryonic days 14 -21) were of lower birth weight (by 12%, P Ͻ 0.01) and displayed full catch-up growth within the first month of postnatal life. DEX-treated male offspring in adulthood selectively displayed elevated plasma adrenocorticotropic hormone (by 221%) and corticosterone (by 188%, P Ͻ 0.05), postprandial insulin-glucose ratios (by 100%, P Ͻ 0.05), and hepatic expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (by 38%, P Ͻ 0.05). Conversely, DEXprogrammed females were hypertensive (by 11%, P Ͻ 0.05), with elevated hepatic angiotensinogen mRNA expression (by 9%, P Ͻ 0.05), plasma angiotensinogen (by 61%, P Ͻ 0.05), and renin activity (by 88%, P Ͻ 0.05). These findings demonstrate that prenatal glucocorticoids program adulthood cardiovascular and metabolic physiology in a gender-specific pattern, and that an activated RAS may in part underlie the hypertension associated with prenatal DEX programming.glucocorticoids; birth weight; hypothalamic-pituitary axis; glucose homeostasis; blood pressure; renin-angiotensin system EPIDEMIOLOGICAL STUDIES in many human populations suggest that the common metabolic and cardiovascular disorders of adult life are influenced by intrauterine factors (7,19). In particular, low birth weight (assumed to be a marker for an adverse intrauterine environment) is associated with a higher frequency of hypertension (5), type 2 diabetes (42), and death from ischemic heart disease in adulthood (7,19,42). The phenomenon of prenatal "programming" has been advanced to explain these findings whereby a factor, acting during a discrete developmental "window," alters the maturation of specific organs, permanently altering their function (6, 10). The systems affected are determined by their particular vulnerability at the time of exposure (54). Although the precise mechanisms underpinning prenatal programming remain elusive, we hypothesized that excessive fetal exposure to glucocorticoids might be important on the basis of the documented effects of antenatal glucocorticoid administration to reduce birth weight and alter the trajectory of maturation of specific fetal organs (24). Glucocorticoid excess in adults or children causes many of the features of the "small baby syndrome." In rats, we and others have shown that prenatal exposure to the synthetic glucocorticoid dexamethasone (DEX) or to endogenous...

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The channels are thought to have structural similarity to ␣-subunits of voltage-gated K ϩ channels, with intracellular amino and carboxy termini and four proteins required for coordination of a single ion pore. As with K ϩ channels, heteromultimerization confers greater diversity. However, unlike voltage-gated K ϩ channels, membrane depolarization is not the primary trigger for channel activity. Instead, chemical factors are considered to be primary stimuli. Details of the chemical sensing properties are becoming apparent and hold promise for revealing further complexity and novelty. In addition, important roles of TRP channels have emerged, including in sensation and cell survival, but we are far from a full appreciation of the purposes of these channels and, in some cases, there is relatively little understanding of TRP family members -one example being TRPM3.

Our data provide important insights into the regulation of pro-inflammatory cytokine expression in human cardiac fibroblasts and suggest that the myocardial anti-inflammatory effects of statins and TZDs are not due to inhibition of TNFalpha-induced IL-1 or IL-6 expression by cardiac fibroblasts.