Curcumin inhibits angiotensin II-induced inflammation and proliferation of rat vascular smooth muscle cells by elevating PPAR-γ activity and reducing oxidative stress.
Angiotensin II (AngII)-induced production of inflammatory factors and proliferation in vascular smooth muscle cells (VSMCs) play an important role in the progression of atherosclerotic plaques. Growing evidence has demonstrated that activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) effectively attenuates AngII-induced inflammation and intercellular reactive oxygen species (iROS) production. Curcumin (Cur) inhibits inflammatory responses by enhancing PPAR-γ activity and reducing oxidative stress in various tissues. The aim of the present study was to ascertain whether Cur inhibits AngII-induced inflammation and proliferation, and its underlying molecular mechanism, in VSMCs. Enzyme-linked immunosorbent assay (ELISA) and real-time PCR were used to measure the protein and mRNA expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Nitric oxide (NO) production was measured by Griess reaction. Western blot analysis and a DNA-binding assay were used to measure PPAR-γ activity. iROS production was measured using the DCFH-DA method. In rat VSMCs, Cur attenuated AngII‑induced expression of IL-6 and TNF-α mRNA and protein in a concentration-dependent manner, inhibited NO production by suppressing inducible NO synthase (iNOS) activity, and suppressed proliferation of VSMCs. This was accompanied by increased PPAR-γ expression and activation in Cur-pretreated VSMCs. GW9662, a PPAR-γ antagonist, reversed the anti-inflammatory effect of Cur. Moreover, Cur attenuated AngII-induced oxidative stress by downregulating the expression of p47phox, which is a key subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. In conclusion, Cur inhibited the expression of IL-6 and TNF-α, decreased the production of NO, and suppressed the proliferation of VSMCs, by elevating PPAR-γ activity and suppressing oxidative stress, leading to attenuated AngII-induced inflammatory responses in VSMCs.
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Hai-Yu
HY
Li
Department of General Medicine, Renji Hospital of Shanghai Jiaotong University, Shanghai 200000, P.R. China.
Mei
M
Yang
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Ze
Z
Li
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Zhe
Z
Meng
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism*; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D047495:PPAR gamma / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005609:Free Radicals; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D000804:Angiotensin II; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D003474:Curcumin