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Antioxidative, antinitrative, and vasculoprotective effects of a peroxisome proliferator-activated receptor-gamma agonist in hypercholesterolemia.

Publication ,  Journal Article
Tao, L; Liu, H-R; Gao, E; Teng, Z-P; Lopez, BL; Christopher, TA; Ma, X-L; Batinic-Haberle, I; Willette, RN; Ohlstein, EH; Yue, T-L
Published in: Circulation
December 2, 2003

BACKGROUND: Peroxisome proliferator-activated receptor (PPAR) signaling pathways have been reported to exert anti-inflammatory effects and attenuate atherosclerosis formation. However, the mechanisms responsible for their anti-inflammatory and antiatherosclerotic effects remain largely unknown. The present study tested the hypothesis that a PPARgamma agonist may exert significant endothelial protection by antioxidative and antinitrative effects. METHODS AND RESULTS: Male New Zealand White rabbits were randomized to receive a normal (control) or a high-cholesterol diet and treated with vehicle or rosiglitazone (a PPARgamma agonist) 3 mg x kg(-1) x d(-1) for 5 weeks beginning 3 weeks after the high-cholesterol diet. At the end of 8 weeks of a high-cholesterol diet, the rabbits were killed, and the carotid arteries were isolated. Bioactive nitric oxide was determined functionally (endothelium-dependent vasodilatation) and biochemically (the phosphorylation of vasodilator-stimulated phosphoprotein, or P-VASP). Vascular superoxide production, PPARgamma, gp91phox, and inducible nitric oxide synthase (iNOS) expression, and vascular ONOO- formation were determined. Hypercholesterolemia caused severe endothelial dysfunction and reduced P-VASP, despite a marked increase in iNOS expression and total NOx production. Treatment with rosiglitazone enhanced PPARgamma expression, improved endothelium-dependent vasodilatation, preserved P-VASP, suppressed gp91phox and iNOS expression, reduced superoxide and total NOx production, and inhibited nitrotyrosine formation. CONCLUSIONS: The PPARgamma agonist rosiglitazone exerted a significant vascular protective effect in hypercholesterolemic rabbits, most likely by attenuation of oxidative and nitrative stresses. The endothelial protective effects of PPARgamma agonists may reduce leukocyte accumulation in vascular walls and contribute to their antiatherosclerotic effect.

Duke Scholars

Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

December 2, 2003

Volume

108

Issue

22

Start / End Page

2805 / 2811

Location

United States

Related Subject Headings

  • Vasodilation
  • Tyrosine
  • Transcription Factors
  • Thiazolidinediones
  • Signal Transduction
  • Rosiglitazone
  • Receptors, Cytoplasmic and Nuclear
  • Rabbits
  • Nitrites
  • Nitric Oxide
 

Citation

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Tao, L., Liu, H.-R., Gao, E., Teng, Z.-P., Lopez, B. L., Christopher, T. A., … Yue, T.-L. (2003). Antioxidative, antinitrative, and vasculoprotective effects of a peroxisome proliferator-activated receptor-gamma agonist in hypercholesterolemia. Circulation, 108(22), 2805–2811. https://doi.org/10.1161/01.CIR.0000097003.49585.5E
Tao, Ling, Hui-Rong Liu, Erhe Gao, Zhi-Ping Teng, Bernard L. Lopez, Theodore A. Christopher, Xin-Liang Ma, et al. “Antioxidative, antinitrative, and vasculoprotective effects of a peroxisome proliferator-activated receptor-gamma agonist in hypercholesterolemia.Circulation 108, no. 22 (December 2, 2003): 2805–11. https://doi.org/10.1161/01.CIR.0000097003.49585.5E.
Tao L, Liu H-R, Gao E, Teng Z-P, Lopez BL, Christopher TA, et al. Antioxidative, antinitrative, and vasculoprotective effects of a peroxisome proliferator-activated receptor-gamma agonist in hypercholesterolemia. Circulation. 2003 Dec 2;108(22):2805–11.
Tao, Ling, et al. “Antioxidative, antinitrative, and vasculoprotective effects of a peroxisome proliferator-activated receptor-gamma agonist in hypercholesterolemia.Circulation, vol. 108, no. 22, Dec. 2003, pp. 2805–11. Pubmed, doi:10.1161/01.CIR.0000097003.49585.5E.
Tao L, Liu H-R, Gao E, Teng Z-P, Lopez BL, Christopher TA, Ma X-L, Batinic-Haberle I, Willette RN, Ohlstein EH, Yue T-L. Antioxidative, antinitrative, and vasculoprotective effects of a peroxisome proliferator-activated receptor-gamma agonist in hypercholesterolemia. Circulation. 2003 Dec 2;108(22):2805–2811.

Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

December 2, 2003

Volume

108

Issue

22

Start / End Page

2805 / 2811

Location

United States

Related Subject Headings

  • Vasodilation
  • Tyrosine
  • Transcription Factors
  • Thiazolidinediones
  • Signal Transduction
  • Rosiglitazone
  • Receptors, Cytoplasmic and Nuclear
  • Rabbits
  • Nitrites
  • Nitric Oxide