Gary D. Lopaschuk

Mitochondrial-targeted therapy with elamipretide preserves cardiac function and prevents late mortality in murine polymicrobial sepsis

Jennie Vu, Cory S. Wagg, Claudia D. Holody, Anson Wong et autres

Abstract Sepsis-induced cardiac dysfunction (SICD) occurs in nearly half of septic patients, is associated with increased mortality, and lacks targeted therapy. Emerging evidence implicates impaired mitochondrial function and metabolic inflexibility as central contributors to myocardial depression. Here, we characterized SICD in a …

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Correction: IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT): a small animal acute myocardial infarction randomized-controlled multicenter study on the effect of ischemic preconditioning

Sauri Hernández‐Reséndiz, Reinis Vilšķe̅rsts, David Aluja, Ioanna Andreadou et autres

In the original article co-authors Gábor B. Brenner, András Makkos, Tamás G. Gergely and Nabil V. Sayour were missing from the author group due to an administrative error on the authors’ part. The authors contributed significantly to the study by generating all …

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Lowering Cardiac Branched-Chain Keto Acid Levels Enhances Cardiac Glucose Oxidation and Cardiac Efficiency via Enhancing Mitochondrial Insulin Signaling in Heart Failure

Qutuba G. Karwi, Liyan Zhang, Keshav Gopal, Cory S. Wagg et autres

BACKGROUND: Elevated levels of cardiac branched-chain amino acids (BCAAs) and their metabolites, namely branched-chain keto acids (BCKAs), contribute to the development of insulin resistance, contractile dysfunction, and adverse remodeling in the failing heart. However, there is still confusion about whether BCAA or …

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Casein Kinase 2α Ablation Confers Protection Against Metabolic Dysfunction‐Associated Steatotic Liver Disease: Role of FUN14 Domain Containing 1‐Dependent Regulation of Mitophagy and Ferroptosis

Ke He, Meixiao Zhan, Xuanming Luo, Ruibin Li et autres

ABSTRACT Mitochondrial dyshomeostasis provokes the onset of metabolic dysfunction‐associated steatotic liver disease (MASLD) although its precise involvement in particular mitophagy in MASLD remains elusive. This work evaluated the role of casein kinase 2α (CK2α) and FUNDC1 in high‐fat diet (HFD)‐evoked MASLD. WT …

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The Crosstalk Between Immune Activation and Metabolism in Heart Failure. A Scientific Statement of the Heart Failure Association of the ESC

Gabriele Fragasso, Davide Stolfo, Markus S. Anker, Antoni Bayés‐Genís et autres

A better understanding of additional mechanisms of heart failure (HF) progression may allow a different and more complete phenotyping of the disease and identification of novel therapeutic targets. Persistent latent myocardial inflammation/immune activation in HF may represent an attempt to restore tissue …

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Sweeteners: erythritol, xylitol and cardiovascular risk—friend or foe?

Bettina K. Wölnerhanssen, Anne Christin Meyer‐Gerspach, Arduino Arduini, Angelo D’Alessandro et autres

Hyperglycaemia harms vascular health and promotes platelet aggregation. Reducing glucose concentration is crucial, and sugar alcohols may aid this effort. Used for over 50 years in food, cosmetic, and pharmaceutical industries, erythritol and xylitol minimally affect plasma glucose and insulin levels while …

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Alterations of Myocardial Ketone Metabolism in Heart Failure with Preserved Ejection Fraction (HFpEF)

Qiuyu Sun, Cory S. Wagg, Nathan Wong, Kaleigh Wei et autres

Abstract Introduction Cardiac energy metabolism is disrupted in heart failure with preserved ejection fraction (HFpEF), as characterized by a switch from glucose oxidation towards fatty acid oxidation. However, although oxidation of ketones is an important source of ATP it remains unclear how …

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Impact of Cholesterol on Cardiac Mitochondrial Function

Gary D. Lopaschuk

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Cardiac energy substrate utilization in heart failure with preserved ejection fraction: reconciling conflicting evidence on fatty acid and glucose metabolism

Lina A. Shehadeh, Emely Robleto, Gary D. Lopaschuk

Direct measurements reveal fatty acid oxidation remains active or increased in HFpEF hearts, whereas glucose oxidation becomes impaired, challenging previous assumptions. Apparent contradictions in HFpEF metabolism literature arise from methodological differences-studies using isolated mitochondria versus intact hearts. Evidence demonstrates fatty acid oxidation …

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Cardiac energy metabolism in diabetes: emerging therapeutic targets and clinical implications

Anjali Panwar, M Adib, Gary D. Lopaschuk

Patients with diabetes are at an increased risk for developing diabetic cardiomyopathy and other cardiovascular complications. Alterations in cardiac energy metabolism in patients with diabetes, including an increase in mitochondrial fatty acid oxidation and a decrease in glucose oxidation, are important contributing …

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IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT): a small animal acute myocardial infarction randomized-controlled multicenter study on the effect of ischemic preconditioning

Sauri Hernández‐Reséndiz, Reinis Vilšķe̅rsts, David Aluja, Ioanna Andreadou et autres

Although many cardioprotective interventions have been shown to limit infarct size (IS), in preclinical animal studies of acute myocardial ischemia/reperfusion injury (IRI), their clinical translation to patient benefit has been largely disappointing. A major factor is the lack of rigor and reproducibility …

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The Impact of Obesity on Cardiac Energy Metabolism and Efficiency in Heart Failure With Preserved Ejection Fraction

Ezra B. Ketema, Gary D. Lopaschuk

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