Effect of Endothelin on Sodium/Hydrogen Exchanger Activity of Human Monocytes and Atherosclerosis‐Related Functions

Koliakos, George; Befani, Christina; Paletas, Konstantinos; Kaloyianni, Martha

doi:10.1196/annals.1397.031

Cited by 20 publications

(17 citation statements)

References 44 publications

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“…The activation of NHE1 increases Na + i , which leads to intracellular Ca 2+ overload via the Na + /Ca 2+ exchanger and plays a crucial role in many diseases, including ischemia [21] and atherosclerosis [22] . We further investigated whether the activation of NHE1 by LPS resulted in increased intracellular calcium levels.…”

Section: Lps Induces Increased Activation Of Nhe1 Activity and Intracmentioning

confidence: 99%

Amiloride attenuates lipopolysaccharide-accelerated atherosclerosis via inhibition of NHE1-dependent endothelial cell apoptosis

et al. 2012

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Aim: To investigate the effects of the potassium-sparing diuretic amiloride on endothelial cell apoptosis during lipopolysaccharide (LPS)-accelerated atherosclerosis. Methods: Human umbilical vein endothelial cells (HUVECs) were exposed to LPS (100 ng/mL) in the presence of drugs tested. The activity of Na + /H + exchanger 1 (NHE1) and calpain, intracellular free Ca 2+ level ([Ca 2+ ] i ), as well as the expression of apoptosis-related proteins in the cells were measured. For in vivo study, ApoE-deficient (ApoE -/-) mice were fed high-fat diets with 0.5% (w/w) amiloride for 4 weeks and LPS (10 µg/mouse) infusion into caudal veins. Afterwards, atherosclerotic lesions, NHE1 activity and Bcl-2 expression in the aortic tissues were evaluated. Results: LPS treatment increased NHE1 activity and [Ca 2+ ] i in HUVECs in a time-dependent manner, which was associated with increased activity of the Ca 2+ -dependent protease calpain. Amiloride (1−10 µmol/L) significantly suppressed LPS-induced increases in NHE1 activity, [Ca 2+ ] i . and calpain activity. In the presence of the Ca 2+ chelator BAPTA (0.5 mmol/L), LPS-induced increase of calpain activity was also abolished. In LPS-treated HUVECs, the expression of Bcl-2 protein was significantly decreased without altering its mRNA level. In the presence of amiloride (10 µmol/L) or the calpain inhibitor ZLLal (50 µmol/L), the down-regulation of Bcl-2 protein by LPS was blocked. LPS treatment did not alter the expression of Bax and Bak proteins in HUVECs. In the presence of amiloride, BAPTA or ZLLal, LPS-induced HUVEC apoptosis was significantly attenuated. In ApoE -/-mice, administration of amiloride significantly suppressed LPS-accelerated atherosclerosis and LPS-induced increase of NHE1 activity, and reversed LPS-induced down-regulation of Bcl-2 expression. Conclusion: LPS stimulates NHE1 activity, increases [Ca 2+ ] i , and activates calpain, which leads to endothelial cell apoptosis related to decreased Bcl-2 expression. Amiloride inhibits NHE1 activity, thus attenuates LPS-accelerated atherosclerosis in mice.

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Section: Lps Induces Increased Activation Of Nhe1 Activity and Intracmentioning

confidence: 99%

Amiloride attenuates lipopolysaccharide-accelerated atherosclerosis via inhibition of NHE1-dependent endothelial cell apoptosis

et al. 2012

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“…1Â10 6 cells/mL) were incubated with the appropriate inhibitors for 15 min at 20 C, followed by incubation with 17b-estradiol for 30 min at 20 C. The cells were then incubated for 10 min on ice and in the dark with 80 mL of an FITC labeled antialpha2 (CD49b) integrin subunit 1:50 diluted as previously described by Koliakos et al [43]. Alpha2 integrin subunit is associated only with b 1 subunit [44e49] and is considered to recognize both laminin-1 and collagen IV [14,50e52].…”

Section: Alpha2 Integrin Subunit (Cd49b) Measurementmentioning

confidence: 99%

Effect of 17β-estradiol on adhesion of Mytilus galloprovincialis hemocytes to selected substrates. Role of alpha2 integrin subunit

Koutsogiannaki

Kaloyianni

2011

Fish & Shellfish Immunology

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“…Several models of cardiac hypertrophy involve signaling through phosphatidylinositide 3 kinase PI3K [9,20,36,37,74,82,102] which in turn participates in the regulation of NHE activity [51,86,87,91].…”

Section: Introductionmentioning

confidence: 99%

Sgk1 sensitivity of Na+/H+ exchanger activity and cardiac remodeling following pressure overload

et al. 2012

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Sustained increase of cardiac workload is known to trigger cardiac remodeling with eventual development of cardiac failure. Compelling evidence points to a critical role of enhanced cardiac Na(+)/H(+) exchanger (NHE1) activity in the underlying pathophysiology. The signaling triggering up-regulation of NHE1 remained, however, ill defined. The present study explored the involvement of the serum- and glucocorticoid-inducible kinase Sgk1 in cardiac remodeling due to transverse aortic constriction (TAC). To this end, experiments were performed in gene targeted mice lacking functional Sgk1 (sgk1 (-/-)) and their wild-type controls (sgk1 (+/+)). Transcript levels have been determined by RT-PCR, cytosolic pH (pH( i )) utilizing 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) fluorescence, Na(+)/H(+) exchanger activity by the Na(+)-dependent realkalinization after an ammonium pulse, ejection fraction (%) utilizing cardiac cine magnetic resonance imaging and cardiac glucose uptake by PET imaging. As a result, TAC increased the mRNA expression of Sgk1 in sgk1 (+/+) mice, paralleled by an increase in Nhe1 transcript levels as well as Na(+)/H(+) exchanger activity, all effects virtually abrogated in sgk1 (-/-) mice. In sgk1 (+/+) mice, TAC induced a decrease in Pgc1a mRNA expression, while Spp1 mRNA expression was increased, both effects diminished in the sgk1 (-/-) mice. TAC was followed by a significant increase of heart and lung weight in sgk1 (+/+) mice, an effect significantly blunted in sgk1 (-/-) mice. TAC increased the transcript levels of Anp and Bnp, effects again significantly blunted in sgk1 (-/-) mice. TAC increased transcript levels of Collagen I and III as well as Ctgf mRNA and CTGF protein abundance, effects significantly blunted in sgk1 (-/-) mice. TAC further decreased the ejection fraction in sgk1 (+/+) mice, an effect again attenuated in sgk1 (-/-) mice. Also, cardiac FDG-glucose uptake was increased to a larger extent in sgk1 (+/+) mice than in sgk1 (-/-) mice after TAC. These observations point to an important role for SGK1 in cardiac remodeling and development of heart failure following an excessive work load.

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Effect of Endothelin on Sodium/Hydrogen Exchanger Activity of Human Monocytes and Atherosclerosis‐Related Functions

Cited by 20 publications

References 44 publications

Amiloride attenuates lipopolysaccharide-accelerated atherosclerosis via inhibition of NHE1-dependent endothelial cell apoptosis

Amiloride attenuates lipopolysaccharide-accelerated atherosclerosis via inhibition of NHE1-dependent endothelial cell apoptosis

Effect of 17β-estradiol on adhesion of Mytilus galloprovincialis hemocytes to selected substrates. Role of alpha2 integrin subunit

Sgk1 sensitivity of Na+/H+ exchanger activity and cardiac remodeling following pressure overload

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