与格列净和Sirtuins有关的线粒体氧化应激引起的代谢综合征和心脏重构。

IF 3.9 2区 医学 Q1 PERIPHERAL VASCULAR DISEASE
Raúl Lelio Sanz, Felipe Inserra, Sebastián García Menéndez, Luciana Mazzei, León Ferder, Walter Manucha
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引用次数: 2

摘要

综述目的:探讨代谢综合征和心血管疾病患者线粒体功能障碍、氧化应激、sirtuins失衡和其他因素的机制途径。钠葡萄糖共转运体2型(SGLT-2)抑制剂深刻影响这些机制。最近的随机临床试验显示在改善心功能和减少心血管和肾脏事件方面有令人印象深刻的结果。这些意想不到的结果使我们需要加深对产生这些效应的分子机制的理解,以帮助解释这些重要的临床结果。最近的研究发现:心血管疾病在代谢综合征和糖尿病患者中非常普遍。此外,线粒体功能障碍是其发展和持续的主要参与者,包括随后的心脏重塑和事件。另一个主角是肾素-血管紧张素系统;高血管紧张素II (Ang II)活性促进氧化应激和局部炎症反应。此外,sirtuins的下降在这一过程中起着关键作用;它们通过调节对细胞环境的适应性反应和在许多情况下与Ang II相互作用来增强氧化应激,包括心脏和血管重构、炎症和纤维化。禁食和较低的线粒体能量产生是大大减少大多数上述心脏代谢综合征紊乱的条件。此外,它增加sirtuins水平,腺苷单磷酸活化蛋白激酶(AMPK)信号刺激缺氧诱导因子-1β (HIF-1 β)并促进酮症。这些作用有利于自噬和线粒体自噬,清除受损的心肌细胞器,减少氧化应激和炎症反应,保护心脏组织。从这个意义上说,SGLT-2抑制剂提高了至少四种sirtuins的水平,其中一些位于线粒体中。此外,最近的证据表明,SLGT-2抑制剂模拟了这一保护过程,改善线粒体功能、氧化应激和炎症。考虑到先前描述的心血管水平的保护,有必要深入了解SGLT-2抑制剂对线粒体功能的影响。这些药物在试验中清楚地显示了各种保护作用,我们简要地描述了它可能取决于sirtuins增强活性,氧化应激减少,炎症过程衰减,间质纤维化减少,以及随之而来的心功能改善。这一信息可以鼓励研究代谢综合征、糖尿病、心脏和肾衰竭以及其他疾病的新治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Metabolic Syndrome and Cardiac Remodeling Due to Mitochondrial Oxidative Stress Involving Gliflozins and Sirtuins.

Metabolic Syndrome and Cardiac Remodeling Due to Mitochondrial Oxidative Stress Involving Gliflozins and Sirtuins.

Purpose of review: To address the mechanistic pathways focusing on mitochondria dysfunction, oxidative stress, sirtuins imbalance, and other contributors in patient with metabolic syndrome and cardiovascular disease. Sodium glucose co-transporter type 2 (SGLT-2) inhibitors deeply influence these mechanisms. Recent randomized clinical trials have shown impressive results in improving cardiac function and reducing cardiovascular and renal events. These unexpected results generate the need to deepen our understanding of the molecular mechanisms able to generate these effects to help explain such significant clinical outcomes.

Recent findings: Cardiovascular disease is highly prevalent among individuals with metabolic syndrome and diabetes. Furthermore, mitochondrial dysfunction is a principal player in its development and persistence, including the consequent cardiac remodeling and events. Another central protagonist is the renin-angiotensin system; the high angiotensin II (Ang II) activity fuel oxidative stress and local inflammatory responses. Additionally, sirtuins decline plays a pivotal role in the process; they enhance oxidative stress by regulating adaptive responses to the cellular environment and interacting with Ang II in many circumstances, including cardiac and vascular remodeling, inflammation, and fibrosis. Fasting and lower mitochondrial energy generation are conditions that substantially reduce most of the mentioned cardiometabolic syndrome disarrangements. In addition, it increases sirtuins levels, and adenosine monophosphate-activated protein kinase (AMPK) signaling stimulates hypoxia-inducible factor-1β (HIF-1 beta) and favors ketosis. All these effects favor autophagy and mitophagy, clean the cardiac cells with damaged organelles, and reduce oxidative stress and inflammatory response, giving cardiac tissue protection. In this sense, SGLT-2 inhibitors enhance the level of at least four sirtuins, some located in the mitochondria. Moreover, late evidence shows that SLGT-2 inhibitors mimic this protective process, improving mitochondria function, oxidative stress, and inflammation. Considering the previously described protection at the cardiovascular level is necessary to go deeper in the knowledge of the effects of SGLT-2 inhibitors on the mitochondria function. Various of the protective effects these drugs clearly had shown in the trials, and we briefly describe it could depend on sirtuins enhance activity, oxidative stress reduction, inflammatory process attenuation, less interstitial fibrosis, and a consequent better cardiac function. This information could encourage investigating new therapeutic strategies for metabolic syndrome, diabetes, heart and renal failure, and other diseases.

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来源期刊
Current Hypertension Reports
Current Hypertension Reports 医学-外周血管病
CiteScore
10.50
自引率
0.00%
发文量
65
审稿时长
6-12 weeks
期刊介绍: This journal intends to provide clear, insightful, balanced contributions by international experts that review the most important, recently published clinical findings related to the diagnosis, treatment, management, and prevention of hypertension. We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas, such as antihypertensive therapies, associated metabolic disorders, and therapeutic trials. Section Editors, in turn, select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. An international Editorial Board reviews the annual table of contents, suggests articles of special interest to their country/region, and ensures that topics are current and include emerging research. Commentaries from well-known figures in the field are also provided.
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