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Seven days of statin treatment improves nitric-oxide mediated endothelial-dependent cutaneous microvascular function in women with endometriosis

Microvasc Res 2022 Aug 12;104421.
Seven days of statin treatment improves nitric-oxide mediated endothelial-dependent cutaneous microvascular function in women with endometriosis
Gabrielle A Dillon 1, Anna E Stanhewicz 2, Corinna Serviente 3, Valerie A Flores 4, Nina Stachenfeld 5, Lacy M Alexander 6
Abstract
Affiliations
  • 1 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.
  • 2 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.
  • 3 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; Department of Kinesiology, University of Massachusetts Amherst, MA, United States of America; Institute for Applied Life Sciences, University of Massachusetts Amherst, MA, United States of America.
  • 4 Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, United States of America.
  • 5 Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, United States of America; John B. Pierce Laboratory, Yale University, New Haven, CT, United States of America.
  • 6 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. Electronic address: lma191@psu.edu.
Abstract
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: 10-10-10-1 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-1) 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.
Keywords: Endometriosis; Microvascular function; Nitric oxide; Women’s health.
Copyright © 2022. Published by Elsevier Inc.
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