Ramanaiah Mamillapalli1, Nikoletta Toffoloni2, Shutaro Habata2, Huang Qunhua3, Rula Atwani2, Nina Stachenfeld2, Hugh S Taylor4. 1. Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT. Electronic address: ramana.mamillapalli@gmail.com. 2. Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT. 3. Department of Surgery (Cardiac Surgery), Yale School of Medicine, New Haven, CT. 4. Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT. Electronic address: hugh.taylor@yale.edu.
Abstract
BACKGROUND: Epidemiologic studies have demonstrated an association between endometriosis and the subsequent development of cardiovascular disease. The direct effect of endometriosis on the progression of atherosclerotic, if any, has not been previously characterized. Endometriosis leads to systemic inflammation that could have consequences for cardiovascular health. Here, we reported the effects of endometriosis on the development of atherosclerosis in a murine model. OBJECTIVE: This study aimed to determine the contribution of endometriosis in promoting cardiovascular disease in a murine model of endometriosis. STUDY DESIGN: Endometriosis was induced in 18 apolipoprotein E-null mice, the standard murine model used to study atherosclerosis. Mice of the same strain were used as controls (n=18) and underwent sham surgery without inducing endometriosis. The formation of endometriotic lesions was confirmed after 25 weeks of induction. Atherosclerotic lesions were subjected to hematoxylin and eosin staining followed by measurement of the aortic root luminal area and wall thickness. The whole aorta was isolated, and Oil Red O staining was performed to quantify the lipid deposits or plaque formation; moreover, biochemical assays were carried out in serum to determine the levels of lipids and inflammatory-related cytokines. RESULTS: Apolipoprotein E mice with endometriosis exhibited increased aortic atherosclerosis compared with controls as measured using Oil Red O staining (7.9% vs 3.1%, respectively; P=.0004). Mice with endometriosis showed a significant 50% decrease in the aortic luminal area compared with sham mice (0.85 mm2 vs 1.46 mm2; P=.03) and a significant increase in aortic root wall thickness (0.22 mm vs 0.15 mm; P=.04). There was no difference in the lipoprotein profile (P<.05) between mice with endometriosis and sham mice. The serum levels of inflammatory cytokines interleukin 1 alpha, interleukin 6, interferon gamma, and vascular endothelial growth factor were significantly (P<.05)increased in the endometriosis mice. CONCLUSION: Our study used a murine model to determine the effect of endometriosis on atherosclerosis. Inflammation-related cytokines interleukin 1 alpha, interleukin 6, interferon gamma, and vascular endothelial growth factor (angiogenic factor) released by endometriotic lesions may contribute to the increased cardiovascular risks in women with endometriosis. To reduce the risk of cardiovascular disease, early identification and treatment of endometriosis are essential. Future treatments targeting inflammatory cytokines may help reduce the long-term risk of cardiovascular disease in women with endometriosis.
BACKGROUND: Epidemiologic studies have demonstrated an association between endometriosis and the subsequent development of cardiovascular disease. The direct effect of endometriosis on the progression of atherosclerotic, if any, has not been previously characterized. Endometriosis leads to systemic inflammation that could have consequences for cardiovascular health. Here, we reported the effects of endometriosis on the development of atherosclerosis in a murine model. OBJECTIVE: This study aimed to determine the contribution of endometriosis in promoting cardiovascular disease in a murine model of endometriosis. STUDY DESIGN: Endometriosis was induced in 18 apolipoprotein E-null mice, the standard murine model used to study atherosclerosis. Mice of the same strain were used as controls (n=18) and underwent sham surgery without inducing endometriosis. The formation of endometriotic lesions was confirmed after 25 weeks of induction. Atherosclerotic lesions were subjected to hematoxylin and eosin staining followed by measurement of the aortic root luminal area and wall thickness. The whole aorta was isolated, and Oil Red O staining was performed to quantify the lipid deposits or plaque formation; moreover, biochemical assays were carried out in serum to determine the levels of lipids and inflammatory-related cytokines. RESULTS: Apolipoprotein E mice with endometriosis exhibited increased aortic atherosclerosis compared with controls as measured using Oil Red O staining (7.9% vs 3.1%, respectively; P=.0004). Mice with endometriosis showed a significant 50% decrease in the aortic luminal area compared with sham mice (0.85 mm2 vs 1.46 mm2; P=.03) and a significant increase in aortic root wall thickness (0.22 mm vs 0.15 mm; P=.04). There was no difference in the lipoprotein profile (P<.05) between mice with endometriosis and sham mice. The serum levels of inflammatory cytokines interleukin 1 alpha, interleukin 6, interferon gamma, and vascular endothelial growth factor were significantly (P<.05)increased in the endometriosis mice. CONCLUSION: Our study used a murine model to determine the effect of endometriosis on atherosclerosis. Inflammation-related cytokines interleukin 1 alpha, interleukin 6, interferon gamma, and vascular endothelial growth factor (angiogenic factor) released by endometriotic lesions may contribute to the increased cardiovascular risks in women with endometriosis. To reduce the risk of cardiovascular disease, early identification and treatment of endometriosis are essential. Future treatments targeting inflammatory cytokines may help reduce the long-term risk of cardiovascular disease in women with endometriosis.