Effects of Dapagliflozin on Myocardial Gene Expression in BTBR Mice with Type 2 Diabetes.

IF 3.1 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Drugs and Therapy Pub Date : 2025-02-01 Epub Date: 2023-11-02 DOI:10.1007/s10557-023-07517-1

Maria Ryaboshapkina, Regina Ye, Yumei Ye, Yochai Birnbaum

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引用次数: 0

Abstract

Background: Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is approved for the treatment of type 2 diabetes, heart failure, and chronic kidney disease. DAPA-HF and DELIVER trial results demonstrate that the cardiovascular protective effect of dapagliflozin extends to non-diabetic patients. Hence, the mechanism-of-action may extend beyond glucose-lowering and is not completely elucidated. We have previously shown that dapagliflozin reduces cardiac hypertrophy, inflammation, fibrosis, and apoptosis and increases ejection fraction in BTBR mice with type 2 diabetes.

Methods: We conducted a follow-up RNA-sequencing study on the heart tissue of these animals and performed differential expression and Ingenuity Pathway analysis. Selected markers were confirmed by RT-PCR and Western blot.

Results: SGLT2 had negligible expression in heart tissue. Dapagliflozin improved cardiac metabolism by decreasing glycolysis and pyruvate utilization enzymes, induced antioxidant enzymes, and decreased expression of hypoxia markers. Expression of inflammation, apoptosis, and hypertrophy pathways was decreased. These observations corresponded to the effects of dapagliflozin in the clinical trials.

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达格列嗪对2型糖尿病BTBR小鼠心肌基因表达的影响。

背景：达格列嗪是一种钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂，已被批准用于治疗2型糖尿病、心力衰竭和慢性肾脏疾病。DAPA-HF和DELIVER试验结果表明，达格列嗪的心血管保护作用扩展到非糖尿病患者。因此，其作用机制可能超出降血糖的范围，尚未完全阐明。我们之前已经表明，达格列嗪可以减少患有2型糖尿病的BTBR小鼠的心脏肥大、炎症、纤维化和细胞凋亡，并增加射血分数。方法：我们对这些动物的心脏组织进行了后续的RNA测序研究，并进行了差异表达和创新途径分析。选择的标记物通过RT-PCR和蛋白质印迹进行确认。结果：SGLT2在心脏组织中的表达可忽略不计。达格列嗪通过降低糖酵解和丙酮酸利用酶来改善心脏代谢，诱导抗氧化酶，并降低缺氧标志物的表达。炎症、细胞凋亡和肥大途径的表达减少。这些观察结果与达格列嗪在临床试验中的作用一致。

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

Cardiovascular Drugs and Therapy 医学-心血管系统

CiteScore

8.30

自引率

0.00%

发文量

110

审稿时长

4.5 months

期刊介绍： Designed to objectively cover the process of bench to bedside development of cardiovascular drug, device and cell therapy, and to bring you the information you need most in a timely and useful format, Cardiovascular Drugs and Therapy takes a fresh and energetic look at advances in this dynamic field. Homing in on the most exciting work being done on new therapeutic agents, Cardiovascular Drugs and Therapy focusses on developments in atherosclerosis, hyperlipidemia, diabetes, ischemic syndromes and arrhythmias. The Journal is an authoritative source of current and relevant information that is indispensable for basic and clinical investigators aiming for novel, breakthrough research as well as for cardiologists seeking to best serve their patients. Providing you with a single, concise reference tool acknowledged to be among the finest in the world, Cardiovascular Drugs and Therapy is listed in Web of Science and PubMed/Medline among other abstracting and indexing services. The regular articles and frequent special topical issues equip you with an up-to-date source defined by the need for accurate information on an ever-evolving field. Cardiovascular Drugs and Therapy is a careful and accurate guide through the maze of new products and therapies which furnishes you with the details on cardiovascular pharmacology that you will refer to time and time again.