The Peroxisome Proliferator-Activated Receptor-Gamma Coactivator-1α-Heme Oxygenase 1 Axis, a Powerful Antioxidative Pathway with Potential to Attenuate Diabetic Cardiomyopathy.
The Peroxisome Proliferator-Activated Receptor-Gamma Coactivator-1α-Heme Oxygenase 1 Axis, a Powerful Antioxidative Pathway with Potential to Attenuate Diabetic Cardiomyopathy.
复制标题
过氧化物酶体增殖物激活受体-γ 辅激活剂-1α-血红素加氧酶 1 轴，一种强大的抗氧化途径，具有减轻糖尿病心肌病的潜力。
DOI：
10.1089/ars.2019.7989
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发表时间：
2020
影响因子：
6.6
通讯作者：
Hochhauser,Edith
中科院分区：
文献类型：
--
作者：
Waldman,Maayan;Arad,Michael;Abraham,NaderG;Hochhauser,Edith
意义：从糖尿病动物模型的研究来看，过氧化物酶体增殖激活受体- γ辅助激活因子-1α (PGC-1α) -血红素加氧酶1 （HO-1）轴的下调似乎是肥胖和糖尿病性心肌病（DCM）发展的关键事件。本文就代谢和生化应激源在啮齿动物和人类DCM病理生理中的作用进行综述。许多心脏病变的一个关键因素是活性氧（ROS）病变的过度产生，它通过损害线粒体功能和直接氧化DNA、蛋白质和脂质膜而导致广泛的细胞损伤。我们讨论了ROS的产生和炎症途径与多种促进和混淆因素导致DCM的作用。最近的进展：对治疗DCM的相关生化途径，特别是热量限制及其与PGC-1α-HO-1轴在DCM衰减中的关系进行了阐明。关键问题：2型糖尿病的患病率增加，这是一种以心肌细胞肥大为特征的独特心肌病的主要原因，没有有效的临床治疗。本文综述了线粒体功能障碍在DCM发展中的作用，以及减轻氧化应激和DCM的潜在氧化靶点。未来方向：靶向PGC-1α-HO-1轴是一种很有希望通过改善线粒体功能和抗氧化防御来改善DCM的方法。本文所述的激活PGC-1α和HO-1的药物诱导剂可能是一种很有前途的临床治疗方法。
Significance:From studies of diabetic animal models, the downregulation of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α)–heme oxygenase 1 (HO-1) axis appears to be a crucial event in the development of obesity and diabetic cardiomyopathy (DCM). In this review, we discuss the role of metabolic and biochemical stressors in the rodent and human pathophysiology of DCM. A crucial contributor for many cardiac pathologies is excessive production of reactive oxygen species (ROS) pathologies, which lead to extensive cellular damage by impairing mitochondrial function and directly oxidizing DNA, proteins, and lipid membranes. We discuss the role of ROS production and inflammatory pathways with multiple contributing and confounding factors leading to DCM.Recent Advances:The relevant biochemical pathways that are critical to a therapeutic approach to treat DCM, specifically caloric restriction and its relation to the PGC-1α–HO-1 axis in the attenuation of DCM, are elucidated.Critical Issues:The increased prevalence of diabetes mellitus type 2, a major contributor to unique cardiomyopathy characterized by cardiomyocyte hypertrophy with no effective clinical treatment. This review highlights the role of mitochondrial dysfunction in the development of DCM and potential oxidative targets to attenuate oxidative stress and attenuate DCM.Future Directions:Targeting the PGC-1α–HO-1 axis is a promising approach to ameliorate DCM through improvement in mitochondrial function and antioxidant defenses. A pharmacological inducer to activate PGC-1α and HO-1 described in this review may be a promising therapeutic approach in the clinical setting.