Increased Activation of Stromal Interaction Molecule-1/Orai-1 in Aorta From Hypertensive Rats

Giachini, Fernanda R.; Chiao, Chin Wei; Carneiro, Fernando S.; Lima, Victor Vitorino; Carneiro, Zidonia N.; Dorrance, Anne M.; Tostes, Rita C.; Webb, R.

doi:10.1161/hypertensionaha.108.124404

Cited by 86 publications

(82 citation statements)

References 46 publications

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“…[17][18][19] However, few reports have studied STIM1-and Orai1-mediated SOCE in SMC other than cultured aortic SMC. 32,33 To our knowledge, the present study is the first to provide evidence for the existence of endogenous STIM1 and Orai1 proteins in rat coronary artery and SMC. We have showed that downregulation of STIM1 and Orai1 prevented UII-induced Ca 21 and Mn 21 entry in the same way as it inhibited SOCE induced by TG.…”

Section: -13mentioning

confidence: 59%

Urotensin-II Signaling Mechanism in Rat Coronary Artery

Domínguez-Rodríguez

Díaz

Rodríguez-Moyano

et al. 2012

ATVB

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Objective-Human urotensin-II (UII) is considered the most potent endogenous vasoconstrictor discovered to date, although the precise mechanism activated downstream of its receptor UTS2R in blood vessels remains elusive. The aim of this study was to determine the role of the store operated Ca 21 entry (SOCE) signaling pathway in UII-induced coronary artery vasoconstriction. Methods and Results-We used a combination of isometric tension measurement, Ca 21 imaging, pharmacology, and molecular approaches to study UII-mediated rat coronary artery vasoconstriction and intracellular Ca 21 mobilization in coronary smooth muscle cells. We found that UII promoted dose-dependent vasoconstriction and elicited Ca 21 and Mn 21 influx, which were sensitive to classical SOCE inhibitors. In addition, knockdown of either STIM1 or Orai1 essentially inhibited UII-mediated SOCE and prevented UII but not high-KCL evoked contraction in transfected coronary artery. Moreover, we found that Ca 21 -independent phospholipase A 2  was involved in UII effects and that is colocalized with STIM1 in different submembrane compartments. Importantly, STIM1 but not Orai1 downregulation inhibits significantly independent phospholipase A 2 activation. Furthermore, lysophosphatidylcholine, an independent phospholipase A 2 product, activated Orai1 but not STIM1-dependent contraction and SOCE. In the present study, we aimed to give further insights into the signaling pathway that mediates the effect of UII in coronary artery with special emphasis on SOCE regulated by STIM1, Orai1, and iPLA 2 . MethodsAn expanded Materials and Methods section detailing the protocols and techniques used in this study can be found in the online-only Data Supplement. Cells and artery PreparationIsolated rat coronary arteries were dissected from the heart of adult male Wistar rats weighing 250 to 450 g and cells culture were prepared as previously described. 16 Isometric tension was measured in rat coronary arterial rings (2 mm) using a small-vessel myograph (JP Trading, Aarhus, Denmark) connected to a digital recorder (Myodataq-2.01, Myodata-2.02 Multi-Myograph System) as previously described. intracellular Ca 21 MeasurementCa 21 and Mn 21 measurement were carried out in isolated SMC loaded with 2 to 5 mol/L fura-2 am using an imagine system (InCyt Im2, Intracellular Imaging, Imsol, UK) equipped with a light-sensitive CCD camera (Cooke PixelFly, ASI, Eugene, OR) as described previously. 16,20,21 results uii Mediates Vasoconstriction through uii receptors, uts2r, in Coronary artery First, we examined the effect of UII on coronary artery contraction. Figure 1A shows that the cumulative application of UII produced a concentration-dependent vasoconstriction in endothelium-denuded coronary arterial rings. Maximal contraction was observed when UII was applied at 100 nmol/L concentration and the EC 50 521.21.3 nmol/L comparing to the vasoconstriction induced by 60 mmol/L KCL. To demonstrate the involvement of UTS2R in UII effects in coronary artery, we first confirmed by West...

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Section: -13mentioning

confidence: 59%

Urotensin-II Signaling Mechanism in Rat Coronary Artery

Domínguez-Rodríguez

Díaz

Rodríguez-Moyano

et al. 2012

ATVB

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“…[18][19][20][21][22][23] Stim1 resides in endoplasmic reticulum and serves as a Ca 2+ sensor, whereas orai1 mainly locates at plasma membrane and functions as a pore-forming component of SOC channel. 19,23 Accumulating evidence has demonstrated that orai1 Ca 2+ channel plays a critical role in regulating T-and B-cell function, 24,25 endothelial and vascular smooth muscle cell proliferation, [26][27][28][29] neutrophil migration, 30 and injury-induced neointima formation. 31 Although the disturbance of these processes have been suggested to be critical for atherogenesis, the functional role of orai-dependent Ca 2+ entry in atherosclerosis formation remains enigmatic.…”

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confidence: 99%

Inhibition of Orai1 Store–Operated Calcium Channel Prevents Foam Cell Formation and Atherosclerosis

Liang¹,

Zeng²,

Mai³

et al. 2016

ATVB

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Objective-To determine the role of orai1 store-operated Ca 2+ entry in foam cell formation and atherogenesis. Approach and Results-Acute administration of oxidized low-density lipoprotein (oxLDL) activates an orai1-dependent Ca 2+ entry in macrophages. Chelation of intracellular Ca 2+, inhibition of orai1 store-operated Ca 2+ entry, or knockdown of orai1 dramatically inhibited oxLDL-induced upregulation of scavenger receptor A, uptake of modified LDL, and foam cell formation. Orai1-dependent Ca 2+ entry induces scavenger receptor A expression and foam cell formation through activation of calcineurin but not calmodulin kinase II. Activation of nuclear factor of activated T cells is not involved in calcineurin signaling to foam cell formation. However, oxLDL dephosohorylates and activates apoptosis signal-regulating kinase 1 in macrophages. Orai1 knockdown prevents oxLDL-induced apoptosis signal-regulating kinase 1 activation. Knockdown of apoptosis signal-regulating kinase 1, or inhibition of its downstream effectors, JNK and p38 mitogenactivated protein kinase, reduces scavenger receptor A expression and foam cell formation. Notably, orai1 expression is increased in atherosclerotic plaques of apolipoprotein E −/− mice fed with high-cholesterol diet. Knockdown of orai1 with adenovirus harboring orai1 siRNA or inhibition of orai1 Ca 2+ entry with SKF96365 for 4 weeks dramatically inhibits atherosclerotic plaque development in high-cholesterol diet feeding apolipoprotein E −/− mice. In addition, inhibition of orai1 Ca 2+ entry prevents macrophage apoptosis in atherosclerotic plaque. Moreover, the expression of inflammatory genes in atherosclerotic lesions and the infiltration of myeloid cells into the aortic sinus plaques are decreased after blocking orai1 signaling. Conclusions-Orai1-dependent

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“…Although both SK and Gd 3+ produce a reduction in blood pressure, these agents were found to exert different actions with respect to VSMC proliferation and [Ca 2+ ] i changes. In this regard, it should be noted that there are three important components in SOCC, namely, a stromal interaction molecule (which is Ca 2+ sensor), a pore forming protein (which allows Ca 2+ influx) and a transient receptor (which regulates the function of SOCC) 31, 32, 33. As all three components of SOCC are important in the control of Ca 2+ influx in VSMC 32, 33, it is likely that the difference in the actions of SK and Gd 3+ on cell proliferation and [Ca 2+ ] i observed in this study may be as a result of their effects on different targeting sites in SOCC.…”

Section: Discussionmentioning

confidence: 99%

Reduction of blood pressure by store‐operated calcium channel blockers

Elimban

Dhalla

2015

J Cellular Molecular Medi

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The voltage‐operated Ca2+ channels (VOCC), which allow Ca2+ influx from the extracellular space, are inhibited by anti‐hypertensive agents such as verapamil and nifedipine. The Ca2+ entering from outside into the cell triggers Ca2+ release from the sarcoplasmic reticulum (SR) stores. To refill the depleted Ca2+ stores in the SR, another type of Ca2+ channels in the cell membrane, known as store‐operated Ca2+ channels (SOCC), are activated. These SOCCs are verapamil and nifedipine resistant, but are SKF 96465 (SK) and gadolinium (Gd3+) sensitive. Both SK and Gd3+ have been shown to reduce [Ca2+]i in the smooth muscle, but their effects on blood pressure have not been reported. Our results demonstrated that both SK and Gd3+ produced a dose‐dependent reduction in blood pressure in rat. The combination of SK and verapamil produced an additive action in lowering the blood pressure. Furthermore, SK, but not Gd3+ suppressed proliferation of vascular smooth muscle cells in the absence or presence of lysophosphatidic acid (LPA). SK decreased the elevation of [Ca2+]i induced by LPA, endothelin‐1 (ET‐1) and angiotensin II (Ang II), but did not affect the norepinephrine (NE)‐evoked increase in [Ca2+]i. On the other hand, Gd3+ inhibited the LPA and Ang II induced change in [Ca2+]i, but had no effect on the ET‐1 and NE induced increase in [Ca2+]i. The combination of verapamil and SK abolished the LPA‐ or adenosine‐5′‐triphosphate (ATP)‐induced [Ca2+]i augmentation. These results suggest that SOCC inhibitors, like VOCC blocker, may serve as promising drugs for the treatment of hypertension.

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Increased Activation of Stromal Interaction Molecule-1/Orai-1 in Aorta From Hypertensive Rats

Cited by 86 publications

References 46 publications

Urotensin-II Signaling Mechanism in Rat Coronary Artery

Urotensin-II Signaling Mechanism in Rat Coronary Artery

Inhibition of Orai1 Store–Operated Calcium Channel Prevents Foam Cell Formation and Atherosclerosis

Reduction of blood pressure by store‐operated calcium channel blockers

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