Seven days of statin treatment improves nitric-oxide mediated endothelial-dependent cutaneous microvascular function in women with endometriosis.
Seven days of statin treatment improves nitric-oxide mediated endothelial-dependent cutaneous microvascular function in women with endometriosis.
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DOI：
10.1016/j.mvr.2022.104421
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发表时间：
2022-11
影响因子：
3.1
通讯作者：
Alexander, Lacy M.
中科院分区：
文献类型：
--
作者：
Dillon, Gabrielle A.;Stanhewicz, Anna E.;Serviente, Corinna;Flores, Valerie A.;Stachenfeld, Nina;Alexander, Lacy M.
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的最初表现之一，但在子宫内膜异位症患者中尚未探讨。HMG-CoA还原酶抑制剂（他汀类药物）发挥有效的抗炎作用，并已被提议作为子宫内膜异位症妇女的预防性治疗。我们假设，微血管内皮功能会受损，否则健康的妇女子宫内膜异位症介导的减少一氧化氮（NO）依赖性扩张和短期他汀类药物管理将改善内皮功能。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，在内皮依赖性激动剂乙酰胆碱（Ach：10−10-10− 1 M）单独和与NO合成酶抑制剂（L-NAME：0.015 M）联合的分级皮内微透析灌注期间连续测量激光多普勒流量（LDF）。6 EN在口服阿托伐他汀（10 mg）7天后重复微透析实验。计算皮肤血管传导率（CVC=LDF*mmHg-1），并标准化为部位特异性最大值（28 mM硝普钠，43°C）。NO依赖性扩张计算为剂量反应曲线下面积之间的差异。子宫内膜异位症患者乙酰胆碱诱导的血管舒张作用减弱（主效应p<0.01），表明内皮功能受损。在子宫内膜异位症女性中，NO依赖性血管舒张也减少（HC：217±120.3 AUC vs. EN：88±97 AUC，p=0.03）。口服阿托伐他汀可改善子宫内膜异位症妇女的乙酰胆碱诱导的（主效应p<0.01）和NO依赖的（295±153 AUC; p=0.05）血管舒张。微循环内皮依赖性血管舒张功能受损的妇女子宫内膜异位症，介导的一部分减少NO。短期口服阿托伐他汀改善内皮依赖性血管舒张，这表明他汀类药物治疗可能是一个可行的干预策略，以减轻加速心血管疾病的风险妇女子宫内膜异位症。
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. 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: 10−10-10−1M) alone and in combination with the NO synthase inhibitor (L-NAME: 0.015M). 6 EN repeated the microdialysis experiment following 7 days of oral atorvastatin treatment (10mg). Cutaneous vascular conductance was calculated (CVC=LDF*mmHg−1) and normalized to site-specific maximum (28mM sodium nitroprusside, 43°C). The NO-dependent dilation was calculated as the difference between the areas under the dose response curves. 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. 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.
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影响因子：
5
作者：
Missmer, SA;Hankinson, SE;Hunter, DJ
通讯作者：
Hunter, DJ
DOI：
10.1152/ajpheart.00179.2020
发表时间：
2020-09-01
影响因子：
4.8
作者：
Dillon, Gabrielle A.;Greaney, Jody L.;Alexander, Lacy M.
通讯作者：
Alexander, Lacy M.
DOI：
10.1161/hypertensionaha.116.08964
发表时间：
2017-05
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Greaney JL;Kutz JL;Shank SW;Jandu S;Santhanam L;Alexander LM
通讯作者：
Alexander LM
影响因子：
2.7
作者：
Alderman, Myles H., III;Yoder, Nicole;Taylor, Hugh S.
通讯作者：
Taylor, Hugh S.
影响因子：
3.6
作者：
Matarazzo, Sara;Quitadamo, Maria Chiara;Biocca, Silvia
通讯作者：
Biocca, Silvia