Aldosterone activates endothelial exocytosis

Jeong, Youngtae; Chaupin, Damian F.; Matsushita, Kazunobu; Yamakuchi, Munekazu; Cameron, Scott J.; Morrell, Craig N.; Lowenstein, Charles J.

doi:10.1073/pnas.0804037106

Cited by 53 publications

(44 citation statements)

References 56 publications

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“…The receptor mechanism mediating aldosterone's endothelial effects (i.e., GPER vs. MR) would be expected to vary across vascular beds and species. MR has been demonstrated in vascular endothelial cells from rat mesenteric arteries (29), rat renal afferent arteries (30), and mouse aortas (26), as well as from human vascular tissues (3,19,26). Furthermore, in a recently reported transgenic mouse model, selective conditional expression of the MR in vascular endothelial cells led to enhanced vasoconstrictor responses (22), effects antithetical to aldosterone's GPER-mediated vasorelaxant effects that we demonstrate in the rat aortic model.…”

Section: Discussionsupporting

confidence: 63%

Aldosterone mediates its rapid effects in vascular endothelial cells through GPER activation

Gros

Ding

Liu

et al. 2013

American Journal of Physiology-Cell Physiology

151

144

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The importance of the rapid vascular effects of aldosterone is increasingly appreciated. Through these rapid pathways, aldosterone has been shown to regulate vascular contractility, cell growth, and apoptosis. In our most recent studies, we demonstrated the effects of aldosterone on cell growth and contractility in vascular smooth muscle cells. We showed that these effects could occur via activation of the classic mineralocorticoid receptor, as well the recently characterized G protein-coupled estrogen receptor (GPER), initially characterized as an estrogen-specific receptor. However, the mechanisms underlying aldosterone's endothelium-dependent actions are unknown. Furthermore, the ERK regulatory and proapoptotic effects of aldosterone mediated by GPER activation in cultured vascular smooth muscle cells were only apparent when GPER was reintroduced into these cells by gene transfer. Whether GPER activation via aldosterone might be an important regulator in native vascular cells has been questioned. Therefore, to determine the role of GPER in mediating aldosterone's effects on cell growth and vascular reactivity in native cells, we examined rat aortic vascular endothelial cells, a model characterized by persistent robust expression of GPER, but without detectable mineralocorticoid receptor expression. In these endothelial cells, the GPER agonist G1 mediates a rapid increase in ERK phosphorylation that is wholly GPER-dependent, paralleling the actions of aldosterone. The effects of G1 and aldosterone to stimulate ERK phosphorylation paralleled their proapoptotic and antiproliferative effects. In previous studies, we reported that aldosterone mediates a rapid endothelium-dependent vasodilatory effect, antagonistic to its direct vasoconstrictor effect in endothelium-denuded preparations. Using a rat aortic ring/organ bath preparation to determine the GPER dependence of aldosterone's endothelium-dependent vasodilator effects, we demonstrate that aldosterone inhibits phenylephrine-mediated contraction. This vasodilator effect parallels the actions of the GPER agonist G1. Furthermore, the effects of aldosterone were completely ablated by the GPER antagonist G15. These data support an important role of GPER activation in aldosterone-mediated regulation of endothelial cell growth, as well as in aldosterone's endothelium-mediated regulation of vasoreactivity.

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Section: Discussionsupporting

confidence: 63%

Aldosterone mediates its rapid effects in vascular endothelial cells through GPER activation

Gros

Ding

Liu

et al. 2013

American Journal of Physiology-Cell Physiology

151

144

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“…Stxbp5 mRNA was expressed in murine tissues, including lung, spleen, and aorta, as measured by quantitative real-time PCR (qPCR; Figure 1B). Stxbp5 mRNA was also found ECs through discrete signaling pathways (37)(38)(39)(40)(41)(42)(43)(44). However, the detailed mechanisms controlling the endothelial SNARE machinery are not fully known.…”

Section: Resultsmentioning

confidence: 99%

“…Adhesion of neutrophils to HUVECs was performed as described previously (36,43,44). HUVECs were transfected with control siRNA or siRNA against STXBP5 in a 12-well plate, then cultured until 100% confluent.…”

Section: Discussionmentioning

confidence: 99%

Syntaxin-binding protein STXBP5 inhibits endothelial exocytosis and promotes platelet secretion

et al. 2014

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“…19,20 The proinflammatory action of aldosterone has been documented further by the recent observation of Weibel-Palade Body exocytosis and the enhanced release of the prothrombotic von Willebrand factor. 21 Alerted by recent reports showing direct CRP actions on human endothelial cells, 5,22,23 we tested the hypothesis that CRP could influence the biomechanical properties of endothelial cells. Some key parameters of endothelial cells were therefore studied by means of atomic force microscopy (AFM) and immunofluorescence techniques.…”

mentioning

confidence: 99%

C-Reactive Protein Makes Human Endothelium Stiff and Tight

Kusche-Vihrog¹,

Urbanová²,

Blanque³

et al. 2011

Hypertension

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Abstract-Elevation of C-reactive protein (CRP) in human blood accompanies inflammatory processes, including cardiovascular diseases. There is increasing evidence that the acute-phase reactant CRP is not only a passive marker protein for systemic inflammation but also affects the vascular system. Further, CRP is an independent risk factor for atherosclerosis and the development of hypertension. Another crucial player in atherosclerotic processes is the mineralocorticoid hormone aldosterone. Even in low physiological concentrations, it stimulates the expression and membrane insertion of the epithelial sodium channel, thereby increasing the mechanical stiffness of endothelial cells. This contributes to the progression of endothelial dysfunction. In the present study, the hypothesis was tested that the acute application of CRP (25 mg/L), in presence of aldosterone (0.5 nmol/L; 24 hour incubation), modifies the mechanical stiffness and permeability of the endothelium. We found that endothelial cells stiffen in response to CRP. In parallel, endothelial epithelial sodium channel is inserted into the plasma membrane, while, surprisingly, the endothelial permeability decreases. CRP actions are prevented either by the inhibition of the intracellular aldosterone receptors using spironolactone (5 nmol/L) or by the inactivation of epithelial sodium channel using specific blockers. In contrast, inhibition of the release of the vasodilating gas nitric oxide via blockade of the phosphoinositide 3-kinase/Akt pathway has no effect on the CRP-induced stiffening of endothelial cells. The data indicate that CRP enhances the effects of aldosterone on the mechanical properties of the endothelium. Thus, CRP could counteract any decrease in arterial blood pressure that accompanies severe acute inflammatory processes. (Hypertension. 2011; 57:231-237.)Key Words: aldosterone Ⅲ CRP Ⅲ ENaC Ⅲ AFM Ⅲ immunofluorescence Ⅲ PI3K Ⅲ NO C -Reactive protein (CRP) is considered to be a stable and powerful inflammatory marker of future cardiovascular risk 1 and, as an acute-phase reactant, originally considered to be a mere marker of vascular inflammation. However, CRP may also participate directly in the inflammatory process. 2 During inflammation and sepsis, the production of NO is increased, which leads to vasodilation and thus to a drop in blood pressure. 3,4 Recently, CRP was shown to decrease endothelial NO synthase expression 5 via inhibition of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, 6 which suggests that it also has a role in endothelial (dys)function. In clinical studies, it has been shown that in patients with essential hypertension, there is a positive correlation between CRP levels and pulse wave velocity, which is a functional indicator for arterial stiffness. 7,8 When the paradigm shift occurred that CRP was not merely a "reporting" but also an "acting" protein, another shift in understanding took place, namely that the mineralocorticoid hormone aldosterone not only acts on the kidney but also on the cardiovascular sys...

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Aldosterone activates endothelial exocytosis

Cited by 53 publications

References 56 publications

Aldosterone mediates its rapid effects in vascular endothelial cells through GPER activation

Aldosterone mediates its rapid effects in vascular endothelial cells through GPER activation

Syntaxin-binding protein STXBP5 inhibits endothelial exocytosis and promotes platelet secretion

C-Reactive Protein Makes Human Endothelium Stiff and Tight

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