Cyclooxygenase inhibition improves endothelial vasomotor dysfunction of visceral adipose arterioles in human obesity


  • 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.

  • Disclosure: The authors have no conflicts of interest with the current manuscript.

  • Author contributions: MGF conceived the study, performed all the vascular experiments, collected adipose samples during surgery, analyzed data, and prepared the manuscript. ST recruited and consented study subjects, and collected adipose samples during surgery. SK assisted with recruitment and in intellectual design. DTMN quantified prostanoids secretion from adipose tissue and assisted in data analysis. BC and DTH were involved in patient recruitment and provided clinical surgical specimens. MAZ and KW performed gene expression analyses and assisted with data analysis and interpretation. JLF assisted with analysis of data. NMH and JAV assisted with data interpretation, scientific direction, and manuscript preparation. CMA was involved in patient recruitment and assisted with intellectual design. NG conceived the overall experimental strategy and design, provided scientific direction, edited the manuscript, and oversaw all aspects of the experimental studies.

Correspondence: Noyan Gokce (



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.