Adipocyte-derived cytokine resistin causes endothelial dysfunction of porcine coronary arteries.
OBJECTIVE
Resistin, a novel adipocyte-derived cytokine, is involved in the development of insulin resistance and diabetes mellitus. In this study, we determined whether resistin could affect vasomotor function, oxidative stress, and endothelial nitric oxide synthase (eNOS) expression in porcine coronary arteries.


METHODS
Porcine coronary arteries were treated with resistin or antioxidant seleno-L-methionine (SeMet). Vasomotor function was studied by using a myograph system. Levels of superoxide anion (O 2 - ) were detected by the lucigenin-enhanced chemiluminescence method. The eNOS mRNA and protein levels were determined by real-time polymerase chain reaction and immunohistochemistry, respectively. Culture of isolated porcine coronary artery endothelial cells (PCAECs) was also included.


RESULTS
Endothelium-dependent relaxation in response to bradykinin was reduced by 15% and 30% for the rings treated with 10 and 40 ng/mL of resistin, respectively, as compared with controls ( P < .05). Endothelium-independent relaxation in response to sodium nitroprusside (SNP) was also reduced by 11% after treatment with 40 ng/mL of resistin ( P < .05). The O 2 - level was increased in the 40 ng/mL resistin-treated vessels by 88% as compared with controls ( P < .05). SeMet reversed these effects. The eNOS mRNA levels in PCAEC cultures treated with resistin (10 and 40 ng/mL) were decreased by 27% and 55%, respectively ( P < .05) and by 39% in the endothelial cells purified from porcine coronary artery rings after treatment with 40 ng/mL of resistin ( P < .05). Immunoreactivity of eNOS in the resistin-treated vessel rings was also substantially reduced.


CONCLUSIONS
Resistin reduces the endothelium-dependent and endothelium-independent vasorelaxation. This effect is associated with increased superoxide radical production, decreased eNOS expression, and is effectively reversed by the antioxidant SeMet.


CONCLUSIONS
Obesity has been considered to be an independent risk factor for coronary artery disease and other vascular lesions. Resistin is a newly discovered adipocyte-derived cytokine, and its plasma levels are increased in obese individuals. However, it is not clear whether resistin could directly contribute to vascular disease formation. This study showed that resistin can cause endothelial dysfunction in porcine coronary arteries through oxidative stress and down-regulation of eNOS. Thus, this study may suggest a new mechanism of obesity-associated vascular disease and that antioxidants may effectively prevent vascular disease in obese individuals.
Kougias
Panagiotis
P
Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, USA.
Chai
Hong
H
Lin
Peter H
PH
Lumsden
Alan B
AB
Yao
Qizhi
Q
Chen
Changyi
C
D000818:Animals; D018929:Cell Culture Techniques; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology*; D006729:Hormones, Ectopic / Q000494:pharmacology*; D023421:Models, Animal; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D052243:Resistin; D013552:Swine; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*
D006729:Hormones, Ectopic; D011994:Recombinant Proteins; D052243:Resistin; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase