ArticleActa pharmacologica Sinica2013
Amiloride attenuates lipopolysaccharide-accelerated atherosclerosis via inhibition of NHE1-dependent endothelial cell apoptosis.
Article in Acta pharmacologica Sinica, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 22 citations in OpenAlex.
- SGLT2 inhibitors prevent LPS-induced M1 macrophage polarization and alleviate inflammatory bowel disease by downregulating NHE1 expression.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- Review
- Downregulating NHE-1 decreases the apoptosis of hippocampal cells in epileptic model rats based on the NHE-1/calpain1 pathway.Heliyon · 2023Article
- miR34a-5p impedes CLOCK expression in chronodisruptive C57BL/6J mice and potentiates pro-atherogenic manifestations.PloS one · 2023Article
- Citronellal Attenuates Oxidative Stress-Induced Mitochondrial Damage through TRPM2/NHE1 Pathway and Effectively Inhibits Endothelial Dysfunction in Type 2 Diabetes Mellitus.Antioxidants (Basel, Switzerland) · 2022Article
- Receptor-independent fluid-phase macropinocytosis promotes arterial foam cell formation and atherosclerosis.Science translational medicine · 2022Article
- Novel Anti-inflammatory Effects of Canagliflozin Involving Hexokinase II in Lipopolysaccharide-Stimulated Human Coronary Artery Endothelial Cells.Cardiovascular drugs and therapy · 2021Article
- NaNature communications · 2019Article
- Expression and regulation of alarmin cytokine IL-1α in human retinal pigment epithelial cells.Experimental eye research · 2018Article
- Article
- Direct Cardiac Actions of Sodium Glucose Cotransporter 2 Inhibitors Target Pathogenic Mechanisms Underlying Heart Failure in Diabetic Patients.Frontiers in physiology · 2018Review
- Proteases in cardiometabolic diseases: Pathophysiology, molecular mechanisms and clinical applications.Biochimica et biophysica acta · 2015Review
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6 authors at 1 institution in 1 country.
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Abstract
aimTo investigate the effects of the potassium-sparing diuretic amiloride on endothelial cell apoptosis during lipopolysaccharide (LPS)-accelerated atherosclerosis.
methodsHuman 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.
resultsLPS 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.
conclusionLPS 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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