Selective estrogen receptor α and β antagonist aggravate cardiovascular dysfunction in type 2 diabetic ovariectomized female rats.

IF 1.1 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Hormone Molecular Biology and Clinical Investigation Pub Date : 2022-12-01 DOI:10.1515/hmbci-2021-0073

Hossein Azizian, Zeinab Farhadi, Mohammad Khaksari

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引用次数: 2

Abstract

Objectives: Type 2 diabetes (T2D) is a major risk factor for cardiovascular disorders (CVD), characterized by pathological diastolic as well as systolic dysfunction, ventricular dilation, and cardiomyocyte hypertrophy. CVD is the main cause of death in postmenopausal women. Estradiol (E2) has protective effects on cardiovascular function. The biological effects of E2 are mainly mediated by classical estrogen receptors (ERs). The present study aimed to investigate the cardioprotective effects of classical ERs in ovariectomized (OVX) diabetic female rats.

Methods: T2D was induced in female rats by high-fat diet feeding along with a low dose of streptozotocin. Then diabetic animals were divided into eight groups: Sham-control, OVX, OVX + Vehicle (Veh), OVX + E2, OVX + E2 + MPP (ERα antagonist), OVX + E2 + PHTPP (ERβ antagonist), OVX + E2 + Veh, OVX + E2 + MPP + PHTPP. Animals received E2, MPP, and PHTPP every four days for 28 days. At the end blood was collected, serum separated, and used for biochemical parameters. Heart tissue was used for cardiac angiotensin II and cytokines measurement.

Results: E2 treatment improved the metabolic disorders caused by T2D, and its receptor antagonists intensified the effects of T2D on the metabolic status. Also, E2 therapy decreased cardiac inflammatory cytokines, and MPP and PHTPP increased cardiac inflammation by increasing TNF-α and IL-6 and decreasing IL-10.

Conclusions: Classical ERs have protective effects on diabetic hearts by improving the metabolic status and inflammatory balance.

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选择性雌激素受体α和β拮抗剂加重2型糖尿病去卵巢雌性大鼠心血管功能障碍。

目的:2型糖尿病(T2D)是心血管疾病(CVD)的主要危险因素，其特征是病理性舒张和收缩功能障碍、心室扩张和心肌细胞肥大。心血管疾病是绝经后妇女死亡的主要原因。雌二醇(E2)对心血管功能有保护作用。E2的生物学效应主要由经典雌激素受体介导。本研究旨在探讨经典雌激素对去卵巢(OVX)糖尿病雌性大鼠的心脏保护作用。方法:采用高脂饲料加低剂量链脲佐菌素诱导雌性大鼠T2D。然后将糖尿病动物分为8组:假对照、OVX、OVX + Vehicle (Veh)、OVX + E2、OVX + E2 + MPP (ERα拮抗剂)、OVX + E2 + PHTPP (ERβ拮抗剂)、OVX + E2 + Veh、OVX + E2 + MPP + PHTPP。动物每4天接受E2、MPP和PHTPP治疗，共28天。最后采集血液，分离血清，用于生化指标。心脏组织用于测量心脏血管紧张素II和细胞因子。结果:E2治疗可改善T2D引起的代谢紊乱，其受体拮抗剂可增强T2D对代谢状态的影响。E2治疗降低心脏炎症因子，MPP和PHTPP通过增加TNF-α和IL-6，降低IL-10增加心脏炎症。结论:经典er通过改善糖尿病心脏的代谢状态和炎症平衡，对糖尿病心脏具有保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hormone Molecular Biology and Clinical Investigation BIOCHEMISTRY & MOLECULAR BIOLOGY-

CiteScore

2.60

自引率

0.00%

发文量

期刊介绍： Hormone Molecular Biology and Clinical Investigation (HMBCI) is dedicated to the provision of basic data on molecular aspects of hormones in physiology and pathophysiology. The journal covers the treatment of major diseases, such as endocrine cancers (breast, prostate, endometrium, ovary), renal and lymphoid carcinoma, hypertension, cardiovascular systems, osteoporosis, hormone deficiency in menopause and andropause, obesity, diabetes, brain and related diseases, metabolic syndrome, sexual dysfunction, fetal and pregnancy diseases, as well as the treatment of dysfunctions and deficiencies. HMBCI covers new data on the different steps and factors involved in the mechanism of hormone action. It will equally examine the relation of hormones with the immune system and its environment, as well as new developments in hormone measurements. HMBCI is a blind peer reviewed journal and publishes in English: Original articles, Reviews, Mini Reviews, Short Communications, Case Reports, Letters to the Editor and Opinion papers. Ahead-of-print publishing ensures faster processing of fully proof-read, DOI-citable articles.