Mitochondrial abnormalities: a hub in metabolic syndrome-related cardiac dysfunction caused by oxidative stress

Abstract

Metabolic syndrome (MetS) refers to a group of cardiovascular risk elements comprising insulin resistance, obesity, dyslipidemia, increased glucose intolerance, and increased blood pressure. Individually, all the MetS components can lead to cardiac dysfunction, while their combination generates additional risks of morbidity and mortality. Growing evidence suggests that oxidative stress, a dominant event in cellular damage and impairment, plays an indispensable role in cardiac dysfunction in MetS. Oxidative stress can not only disrupt mitochondrial activity through inducing oxidative damage to mitochondrial DNA, RNA, lipids, and proteins but can also impair cardiomyocyte contractile function via mitochondria-related oxidative modifications of proteins central to excitation-contraction coupling. Furthermore, excessive reactive oxygen species (ROS) generation can lead to the activation of several mitochondria apoptotic signaling pathways, release of cytochrome c, and eventual induction of myocardial apoptosis. This review will focus on such processes of mitochondrial abnormalities in oxidative stress induced cardiac dysfunction in MetS.

Keywords: Cardiac dysfunction; Metabolic syndrome; Mitochondria; Oxidative stress; Reactive oxygen species.

Fig. 1

Mitochondria act as a key regulator in metabolic heart disease caused by oxidative stress. Three possible mechanisms of mitochondria involving in this process are summarized: ROS mediate oxidative damage to mitochondrial DNA, RNA, and proteins, resulting in ETC function impairment. The mitochondria-related oxidative modifications of ${\mathit{Ca}}^{2+}$ channels and transporters can directly cause cardiomyocyte systolic and diastolic dysfunction. Excessive ROS induce mitochondria-dependent cardiomyocyte apoptosis by activating proapoptotic signaling pathways, suppressing antiapoptotic signaling pathways, and mediating cytochrome c release. ROS reactive oxygen species, CVD cardiovascular disease, mtDNA mitochondrial DNA, ETC electron transport chain