Curcumin reduces angiotensin II-mediated cardiomyocyte growth via LOX-1 inhibition.
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.
Kang
Bum-Yong
BY
Department of Internal Medicine, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, AR 72205-7199, USA.
Khan
Junaid A
JA
Ryu
Sunhyo
S
Shekhar
Rahul
R
Seung
Ki-Bae
KB
Mehta
Jawahar L
JL
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000235:genetics; D049108:Cell Enlargement / Q000187:drug effects*; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D019808:Losartan / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D021122:Protein Subunits / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D051127:Scavenger Receptors, Class E / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection
D000906:Antibodies; D008562:Membrane Glycoproteins; D016328:NF-kappa B; C495138:Olr1 protein, mouse; D021122:Protein Subunits; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D051127:Scavenger Receptors, Class E; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D003474:Curcumin; D019808:Losartan