Curcumin reduces angiotensin II-mediated cardiomyocyte growth via LOX-1 inhibition. - GreenMedInfo Summary
Curcumin reduces angiotensin II-mediated cardiomyocyte growth via LOX-1 inhibition.
J Cardiovasc Pharmacol. 2010 Apr;55(4):417-24. PMID: 20422739
Department of Internal Medicine, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, AR 72205-7199, USA.
BACKGROUND: Curcumin, a natural polyphenolic compound, has been shown to reduce cardiomyocyte growth. Angiotensin II type 1 receptor (AT1R) and lectin-like oxidized low density lipoprotein (ox-LDL) receptor-1 (LOX-1) are major stimuli for cardiomyocyte growth via activation of oxidant signals. We postulated that curcumin may reduce Ang II-mediated cardiomyocyte growth via AT1R and LOX-1 inhibition.
METHODS: Adult mouse cardiomyocytes (HL-1) were incubated overnight in serum-free medium, and then treated with solvents or curcumin, the AT1R inhibitor losartan or anti-LOX-1 antibody for 3 hours, and the cells were then stimulated with Ang II. We measured cardiomyocyte growth, and associated intracellular redox signals using reverse transcriptase-polymerase chain reaction and quantitative real-time RT-PCR. We also examined the effect of curcumin on cardiomyocyte biology with forced overexpression of LOX-1 gene.
RESULTS: Curcumin (5-10 microM), losartan, and anti-LOX-1 antibody markedly attenuated Ang II-mediated oxidant stress, and the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and nuclear factor-kappaB (NF-kappaB). Attenuation of redox state by curcumin resulted in abrogation of Ang II-mediated cardiomyocyte growth and atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) genes. Curcumin also reduced Ang II-mediated upregulation of AT1R and LOX-1. The forced upregulation of LOX-1 enhanced the expression of genes for AT1R, ANP, and BNP, and curcumin pretreatment reduced LOX-1 and AT1R expression and LOX-1-mediated increase in hypertrophy markers.
CONCLUSIONS: Curcumin attenuates Ang II-mediated cardiomyocyte growth by inhibiting LOX-1 and AT1R expression and suppressing the heightened intracellular redox state.