bims-carmet 2022-01-02 papers

Issue of 2022‒01‒02
four papers selected by
Mikky Atsér
University of British Columbia

Front Cardiovasc Med. 2021 ;8 789267

Mitochondrial Metabolism in Myocardial Remodeling and Mechanical Unloading: Implications for Ischemic Heart Disease.

Min Jiang, Xiaoye Xie, Feng Cao, Yabin Wang.

Ischemic heart disease refers to myocardial degeneration, necrosis, and fibrosis caused by coronary artery disease. It can lead to severe left ventricular dysfunction (LVEF ≤ 35-40%) and is a major cause of heart failure (HF). In each contraction, myocardium is subjected to a variety of mechanical forces, such as stretch, afterload, and shear stress, and these mechanical stresses are clinically associated with myocardial remodeling and, eventually, cardiac outcomes. Mitochondria produce 90% of ATP in the heart and participate in metabolic pathways that regulate the balance of glucose and fatty acid oxidative phosphorylation. However, altered energetics and metabolic reprogramming are proved to aggravate HF development and progression by disturbing substrate utilization. This review briefly summarizes the current insights into the adaptations of cardiomyocytes to mechanical stimuli and underlying mechanisms in ischemic heart disease, with focusing on mitochondrial metabolism. We also discuss how mechanical circulatory support (MCS) alters myocardial energy metabolism and affects the detrimental metabolic adaptations of the dysfunctional myocardium.

Keywords: heart failure; ischemic heart disease; left ventricular assist device; mechanical unloading; mitochondrial metabolism; veno-arterial ECMO

DOI: https://doi.org/10.3389/fcvm.2021.789267

Interv Cardiol (Lond). 2021 ;13(6): 415-424

The promise and problems of metabolic-based therapies for heart failure.

Dianne M Perez.

Despite standard therapies, heart failure patients have high rates of morbidity highlighting the need to develop alternative therapeutic approaches. Heart failure has been described as an energy-starved condition that is hypothesized to drive the pathological remodeling of the heart. Numerous studies have described the metabolic defects that occur when the heart fails and adaptive changes that take place to maintain the energy needed for the heart to function properly. In this review we will summarize the metabolic requirements of a normal heart and what happens during failure. We will also summarize the various metabolic therapeutic strategies that have been developed over the years to treat heart failure and their results from clinical trials.

Keywords: Adrenergic receptor; Heart failure; Metabolism; Myocyte

Front Nutr. 2021 ;8 783164

The Pyruvate Dehydrogenase Complex in Sepsis: Metabolic Regulation and Targeted Therapy.

Zhenhua Zeng, Qiaobing Huang, Liangfeng Mao, Jie Wu, Sheng An, Zhongqing Chen, Weijin Zhang.

Anaerobic glycolysis is the process by which glucose is broken down into pyruvate and lactate and is the primary metabolic pathway in sepsis. The pyruvate dehydrogenase complex (PDHC) is a multienzyme complex that serves as a critical hub in energy metabolism. Under aerobic conditions, pyruvate translocates to mitochondria, where it is oxidized into acetyl-CoA through the activation of PDHC, thereby accelerating aerobic oxidation. Both phosphorylation and acetylation affect PDHC activity and, consequently, the regulation of energy metabolism. The mechanisms underlying the protective effects of PDHC in sepsis involve the regulation on the balance of lactate, the release of inflammatory mediators, the remodeling of tricarboxylic acid (TCA) cycle, as well as on the improvement of lipid and energy metabolism. Therapeutic drugs that target PDHC activation for sepsis treatment include dichloroacetate, thiamine, amrinone, TNF-binding protein, and ciprofloxacin. In this review, we summarize the recent findings regarding the metabolic regulation of PDHC in sepsis and the therapies targeting PDHC for the treatment of this condition.

Keywords: glycolysis; metabolism; pyruvate dehydrogenase complex; sepsis; therapy

DOI: https://doi.org/10.3389/fnut.2021.783164

Eur Heart J Cardiovasc Imaging. 2021 Dec 27. pii: jeab277. [Epub ahead of print]

Oxidative metabolism and cardiac work in different heart failure phenotypes.

Antti Saraste, Juhani Knuuti.

DOI: https://doi.org/10.1093/ehjci/jeab277