Curcumin reduces angiotensin II-mediated cardiomyocyte growth via LOX-1 inhibition

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Natural Product Chemistry

Background:

• Curcumin, a natural polyphenol, is known to inhibit cardiomyocyte growth.
• Angiotensin II type 1 receptor (AT1R) and LOX-1 receptor are key mediators of cardiomyocyte hypertrophy via oxidant signals.
• This study investigates curcumin's potential to inhibit Ang II-mediated cardiomyocyte growth through AT1R and LOX-1 pathways.

Purpose of the Study:

• To determine if curcumin can reduce Angiotensin II (Ang II)-induced cardiomyocyte growth.
• To elucidate the mechanisms by which curcumin affects AT1R and LOX-1 signaling.
• To assess curcumin's impact on intracellular redox state and associated gene expression.

Main Methods:

• Adult mouse cardiomyocytes (HL-1) were treated with curcumin, losartan (AT1R inhibitor), or anti-LOX-1 antibody.
• Cells were stimulated with Ang II, and cardiomyocyte growth was measured.
• Intracellular redox signals, NADPH oxidase, NF-kappaB, AT1R, LOX-1, ANP, and BNP gene expression were analyzed via RT-PCR and qPCR.
• The effect of curcumin was also assessed in cells with forced LOX-1 overexpression.

Main Results:

• Curcumin, losartan, and anti-LOX-1 antibody attenuated Ang II-induced oxidant stress and expression of NADPH oxidase and NF-kappaB.
• Curcumin's suppression of redox state abrogated Ang II-mediated cardiomyocyte growth and ANP/BNP gene expression.
• Curcumin reduced Ang II-induced upregulation of AT1R and LOX-1.
• Forced LOX-1 upregulation increased AT1R, ANP, and BNP expression, which was reduced by curcumin pretreatment.

Conclusions:

• Curcumin effectively attenuates Ang II-mediated cardiomyocyte growth.
• Curcumin inhibits the expression of LOX-1 and AT1R, key receptors involved in cardiac hypertrophy.
• Curcumin suppresses the heightened intracellular redox state, providing a mechanism for its cardioprotective effects.