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, 72205-7199, USA.
Khan
Junaid A
JA
Ryu
Sunhyo
S
Shekhar
Rahul
R
Seung
Ki-Bae
KB
Mehta
Jawahar L
JL
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D049108:Cell Enlargement / Q000187:drug effects*; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D051127:Scavenger Receptors, Class E / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D006131:Growth Inhibitors; C495138:Olr1 protein, mouse; D044140:Receptor, Angiotensin, Type 1; D051127:Scavenger Receptors, Class E; D000804:Angiotensin II; D003474:Curcumin