七天的他汀类药物治疗可改善子宫内膜异位症女性的一氧化氮介导的内皮依赖性皮肤微血管功能。
Seven days of statin treatment improves nitric-oxide mediated endothelial-dependent cutaneous microvascular function in women with endometriosis.
机构信息
Noll Laboratory, Department of Kinesiology, The Pennsylvania State University, University Park, PA, United States of America; Center for Healthy Aging, The Pennsylvania State University, University Park, PA, United States of America.
Noll Laboratory, Department of Kinesiology, The Pennsylvania State University, University Park, PA, United States of America; Department of Health and Human Physiology, The University of Iowa, Iowa City, IA, United States of America.
出版信息
Microvasc Res. 2022 Nov;144:104421. doi: 10.1016/j.mvr.2022.104421. Epub 2022 Aug 12.
INTRODUCTION
Endometriosis is associated with systemic inflammation and increased risk of cardiovascular disease (CVD). Endothelial dysfunction is one of the first manifestations of CVD but is unexplored in women with endometriosis. HMG-CoA-reductase inhibitors (statins) exert potent anti-inflammatory effects, and have been proposed as an adjunctive therapy in women with endometriosis. We hypothesized that microvascular endothelial function would be impaired in otherwise healthy women with endometriosis mediated by reduced nitric oxide (NO)-dependent dilation and that short term statin administration would improve endothelial function.
METHODS
In 8 healthy control (HC: 33 ± 9 yr) and 8 women with endometriosis (EN: 34 ± 9 yr), laser-Doppler flux (LDF) was measured continuously during graded intradermal microdialysis perfusion of the endothelium-dependent agonist acetylcholine (Ach: 10-10 M) alone and in combination with the NO synthase inhibitor (L-NAME: 0.015 M). 6 EN repeated the microdialysis experiment following 7 days of oral atorvastatin treatment (10 mg). Cutaneous vascular conductance was calculated (CVC = LDF*mmHg) and normalized to site-specific maximum (28 mM sodium nitroprusside, 43 °C). The NO-dependent dilation was calculated as the difference between the areas under the dose response curves.
RESULTS
Ach-induced vasodilation was blunted in women with endometriosis (main effect p < 0.01), indicating impaired endothelial function. NO-dependent vasodilation was also reduced in women with endometriosis (HC: 217 ± 120.3 AUC vs. EN: 88 ± 97 AUC, p = 0.03). Oral atorvastatin improved Ach-induced (main effect p < 0.01) and NO-dependent (295 ± 153 AUC; p = 0.05) vasodilation in women with endometriosis.
CONCLUSION
Microcirculatory endothelium-dependent vasodilation is impaired in women with endometriosis, mediated in part by reductions in NO. Short-term oral atorvastatin improved endothelium-dependent vasodilation, suggesting that statin therapy may be a viable intervention strategy to mitigate accelerated CVD risk in women with endometriosis.
简介
子宫内膜异位症与全身炎症和心血管疾病（CVD）风险增加有关。内皮功能障碍是 CVD 的最早表现之一，但在子宫内膜异位症患者中尚未得到探索。HMG-CoA 还原酶抑制剂（他汀类药物）具有强大的抗炎作用，并被提议作为子宫内膜异位症患者的辅助治疗。我们假设，通过减少一氧化氮（NO）依赖性扩张，健康的子宫内膜异位症女性的微血管内皮功能会受损，并且短期他汀类药物治疗会改善内皮功能。
方法
在 8 名健康对照（HC：33±9 岁）和 8 名子宫内膜异位症患者（EN：34±9 岁）中，通过激光多普勒通量（LDF）连续测量内皮依赖性激动剂乙酰胆碱（Ach：10-10 M）单独和与一氧化氮合酶抑制剂（L-NAME：0.015 M）联合经皮微透析灌注时的变化。6 名 EN 在口服阿托伐他汀治疗（10 mg）7 天后重复微透析实验。计算皮肤血管传导率（CVC = LDF*mmHg），并归一化为特定部位的最大值（28 mM 硝普钠，43°C）。NO 依赖性扩张通过剂量反应曲线下面积的差异来计算。
结果
子宫内膜异位症患者的 Ach 诱导血管舒张减弱（主要效应 p <0.01），表明内皮功能受损。子宫内膜异位症患者的 NO 依赖性血管舒张也减少（HC：217±120.3 AUC 与 EN：88±97 AUC，p =0.03）。口服阿托伐他汀可改善子宫内膜异位症患者 Ach 诱导的（主要效应 p <0.01）和 NO 依赖性（295±153 AUC；p =0.05）血管舒张。
结论
子宫内膜异位症女性的微血管内皮依赖性血管舒张受损，部分由 NO 减少介导。短期口服阿托伐他汀可改善内皮依赖性血管舒张，表明他汀类药物治疗可能是减轻子宫内膜异位症女性加速 CVD 风险的可行干预策略。
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