Aldosterone augments LOX-1-mediated low-density lipoprotein uptake in human umbilical artery endothelial cells.
Aldosterone and oxidized low-density lipoprotein (oxLDL) are recognized risk factors for cardiovascular disease and atherosclerosis. LOX-1 is a multi-ligand receptor originally identified as the endothelial oxLDL receptor, which mediates the uptake of oxLDL and plays a role in early atherosclerosis. The present study aimed to investigate the pathophysiological relevance of LOX-1 in aldosterone-induced atherosclerosis. The effect of aldosterone on LOX-1 expression and LDL uptake in primary cultures of human umbilical artery endothelial cells (HUAECs) was investigated in the absence and presence of the mineralocorticoid receptor (MR) antagonist spironolactone (Spiro). Aldosterone increased both mRNA and protein expression of LOX-1 in a dose-dependent manner with a maximum effect reached 24 h after treatment. Increased LOX-1 expression was associated with an augmented uptake of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil)-labeled LDL(5 muM/ml, 3h). However, pretreatment with Spiro (1 muM) almost reduced these effects. Additionally, an increase in MR expression was detected in response to aldosterone in HUAECs. Collectively, our study demonstrates that aldosterone promotes LOX-1-mediated LDL uptake in human endothelial cells, and Spiro effectively inhibited these effects, suggesting that MR inhibition may be considered as a new anti-atherosclerotic therapy.
Taye
Ashraf
A
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, Minia, Egypt. Ashraf_taye70@yahoo.com
Sawamura
Tatsuya
T
Morawietz
Henning
H
D000450:Aldosterone / Q000494:pharmacology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D000451:Mineralocorticoid Receptor Antagonists; D012333:RNA, Messenger / Q000032:analysis; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000502:physiology*; D014469:Umbilical Arteries / Q000378:metabolism
D008077:Lipoproteins, LDL; D000451:Mineralocorticoid Receptor Antagonists; C495137:OLR1 protein, human; D012333:RNA, Messenger; D051127:Scavenger Receptors, Class E; D000450:Aldosterone