Disclosure: The authors have no conflicts of interest with the current manuscript.
Cyclooxygenase inhibition improves endothelial vasomotor dysfunction of visceral adipose arterioles in human obesity
Article first published online: 29 JUL 2013
Copyright © 2013 The Obesity Society
How to Cite
Farb, M. G., Tiwari, S., Karki, S., Ngo, D. T.M., Carmine, B., Hess, D. T., Zuriaga, M. A., Walsh, K., Fetterman, J. L., Hamburg, N. M., Vita, J. A., Apovian, C. M. and Gokce, N. (2013), Cyclooxygenase inhibition improves endothelial vasomotor dysfunction of visceral adipose arterioles in human obesity. Obesity. doi: 10.1002/oby.20505
Funding agencies: Dr. Gokce is supported by National Institutes of Health (NIH) grants HL1145675, and HL084213. Dr. Farb is supported by an American Heart Association Postdoctoral Fellowship grant 12POST11780028. Dr. Walsh is supported by NIH grants HL068758 and AG034972. Dr. Vita is supported by NIH grants HL083801, HL083269, HL75795, and K12 HL083781. Dr. Hamburg is supported by NIH grants HL109790 and HL102299. Dr. Fetterman is supported by NIH grant T32 HL07224. Drs. Walsh, Gokce, and Vita are jointly supported by NIH grant P01 HL081587.
- Article first published online: 29 JUL 2013
- Accepted manuscript online: 3 MAY 2013 03:49AM EST
- Manuscript Accepted: 24 APR 2013
- Manuscript Received: 21 DEC 2012
The purpose of this study was to determine whether cyclooxygenase inhibition improves vascular dysfunction of adipose microvessels from obese humans.
Design and Methods
In 20 obese subjects (age 37 ± 12 years, BMI 47 ± 8 kg/m2), subcutaneous and visceral fat were collected during bariatric surgery and characterized for adipose depot-specific gene expression, endothelial cell phenotype, and microvascular function. Vasomotor function was assessed in response to endothelium-dependent agonists using videomicroscopy of small arterioles from fat.
Arterioles from visceral fat exhibited impaired endothelium-dependent, acetylcholine-mediated vasodilation, compared to the subcutaneous depot (P < 0.001). Expression of mRNA transcripts relevant to the cyclooxygenase pathway was upregulated in visceral compared to subcutaneous fat. Pharmacological inhibition of cyclooxygenase with indomethacin improved endothelium-dependent vasodilator function of arterioles from visceral fat by twofold (P = 0.01), whereas indomethacin had no effect in the subcutaneous depot. Indomethacin increased activation via serine-1177 phosphorylation of endothelial nitric oxide synthase in response to acetylcholine in endothelial cells from visceral fat. Inhibition of endothelial nitric oxide synthase with Nω-nitro-l-arginine methyl ester abrogated the effects of cyclooxygenase-inhibition suggesting that vascular actions of indomethacin were related to increased nitric oxide bioavailability.
Our findings suggest that cyclooxygenase-mediated vasoconstrictor prostanoids partly contribute to endothelial dysfunction of visceral adipose arterioles in human obesity.