Qatar Analytics and BioResearch Lab, Anti-Doping Lab Qatar, Qatar.
Metabolic and Bariatric Surgery Department, Hamad Medical Corporation, Doha, Qatar.
Life Sci. 2019 Dec 15;239:117039. doi: 10.1016/j.lfs.2019.117039. Epub 2019 Nov 6.
Obesity is a risk factor for endothelial dysfunction, the severity of which is likely to vary depending on extent and impact of adiposity on the vasculature. This study investigates the roles of cyclooxygenase isoforms and thromboxane receptor activities in the differential endothelial dilatory capacities of arteries derived from omental and subcutaneous adipose tissues in obesity.
Small arteries were isolated from omental and subcutaneous adipose tissues obtained from consented morbidly obese patients (n = 65, BMI 45 ± 6 kg m [Mean ± SD]) undergoing bariatric surgery. Relaxation to acetylcholine was studied by wire myography in the absence or presence of indomethacin (10 μM, cyclooxygenase inhibitor), FR122047 (1 μM, cyclooxygenase-1 inhibitor), Celecoxib (4 μM, cyclooxygenase-2 inhibitor), Nω-Nitro-L-arginine methyl ester (L-NAME, 100 μM, nitric oxide synthase inhibitor) or combination of apamin (0.5 μM) and charybdotoxin (0.1 μM) that together inhibit endothelium-derived hyperpolarizing factor (EDHF). Contractions to U46619 (thromboxane A mimetic) were also studied.
Acetylcholine relaxation was significantly attenuated in omental compared with subcutaneous arteries from same patients (p < 0.01). Indomethacin (p < 0.01) and FR122047 (p < 0.001) but not Celecoxib significantly improved the omental arteriolar relaxation. Cyclooxygenase-1 mRNA and U46619 contractions were both increased in omental compared with subcutaneous arteries (p < 0.05). L-NAME comparably inhibited acetylcholine relaxation in both arteries, while apamin+charybdotoxin were less effective in omental compared with subcutaneous arteries.
The results show that the depot-specific reduction in endothelial dilatory capacity of omental compared with subcutaneous arteries in obesity is in large part due to altered cyclooxygenase-1 and enhanced thromboxane receptor activities, which cause EDHF deficiency.
肥胖是内皮功能障碍的一个危险因素，其严重程度可能因脂肪堆积对血管的程度和影响而有所不同。本研究旨在探讨环氧合酶同工酶和血栓素受体活性在肥胖患者内脏脂肪组织和皮下脂肪组织来源的小动脉内皮舒张能力差异中的作用。
从接受减肥手术的病态肥胖患者（n=65，BMI 45±6kg/m²）的内脏脂肪组织和皮下脂肪组织中分离出小动脉。在不存在或存在吲哚美辛（10μM，环氧合酶抑制剂）、FR122047（1μM，环氧合酶-1 抑制剂）、塞来昔布（4μM，环氧合酶-2 抑制剂）、Nω-硝基-L-精氨酸甲酯（L-NAME，100μM，一氧化氮合酶抑制剂）或组合应用阿帕米（0.5μM）和沙蟾毒精（0.1μM）的情况下，通过线描肌动描记术研究乙酰胆碱的舒张作用，阿帕米和沙蟾毒精联合应用可抑制内皮衍生超极化因子（EDHF）。还研究了 U46619（血栓素 A 模拟物）引起的收缩反应。
与来自同一患者的皮下动脉相比，内脏脂肪组织来源的动脉对乙酰胆碱的舒张反应明显减弱（p<0.01）。吲哚美辛（p<0.01）和 FR122047（p<0.001）而非塞来昔布显著改善了内脏脂肪小动脉的舒张反应。与皮下动脉相比，环氧合酶-1 mRNA 和 U46619 收缩在内脏脂肪组织中均增加（p<0.05）。L-NAME 对两种动脉的乙酰胆碱舒张反应均有类似的抑制作用，而阿帕米+沙蟾毒精对内脏脂肪组织的作用比对皮下动脉的作用小。
结果表明，肥胖患者内脏脂肪组织与皮下脂肪组织来源的小动脉内皮舒张能力的局部减少在很大程度上归因于环氧合酶-1 活性改变和血栓素受体活性增强，导致 EDHF 缺乏。
