bims-hafaim 2025-02-09 papers

Issue of 2025–02–09
three papers selected by
Kyle McCommis, Saint Louis University

Can J Cardiol. 2025 Jan 30. pii: S0828-282X(25)00099-6. [Epub ahead of print]

The impact of obesity on cardiac energy metabolism and efficiency in heart failure with preserved ejection fraction.

The incidence and prevalence of heart failure with preserved ejection fraction (HFpEF) continues to rise, and now comprises over half of all heart failure cases. There are many risk factors for HFpEF, including older age, hypertension, diabetes, dyslipidemia, sedentary behaviour, and obesity. The rising prevalence of obesity in society is a particularly important contributor to HFpEF development and severity. Obesity can adversely affect the heart, including inducing marked alterations in cardiac energy metabolism. This includes obesity-induced impairments in mitochondrial function, and an increase in fatty acid uptake and mitochondrial fatty acid ß-oxidation. This increase in myocardial fatty acid metabolism is accompanied by an impaired myocardial insulin signalling and a marked decrease in glucose oxidation. This switch from glucose to fatty acid metabolism decreases cardiac efficiency and can contribute to severity of HFpEF. Increased myocardial fatty acid uptake in obesity is also associated with the accumulation of fatty acids, resulting in cardiac lipotoxicity. Obesity also results in dramatic changes in the release of adipokines, which can negatively impact cardiac function and energy metabolism. Obesity-induced increases in epicardial fat can also increase cardiac insulin resistance and negatively impact cardiac energy metabolism and HFpEF. However, optimizing cardiac energy metabolism in obese subjects may be one approach to preventing and treating HFpEF. This review discusses what is presently known about the effects of obesity on cardiac energy metabolism and insulin signaling in HFpEF. The clinical implications of obesity and energy metabolism on HFpEF are also discussed.

Keywords: epicardial fat; fatty acid oxidation; glucose oxidation; lipotoxicity; mitochondria

DOI: https://doi.org/10.1016/j.cjca.2025.01.029

Nucleosides Nucleotides Nucleic Acids. 2025 Feb 02. 1-12

Pharmacological interventions that activate mitochondrial biogenesis stimulate nucleotide generation in isoproterenol-stressed rat cardiomyocytes.

Alicja Braczko, Klaudia Stawarska, Ada Kawecka, Iga Walczak, Ewa M Slomińska, Barbara Kutryb-Zając, Ryszard T Smoleński.

Mitochondrial dysfunction in failing hearts has been described as a driving force for energy deprivation and cardiomyocyte energy supply-demand imbalance. Isoproterenol (ISO), the β1/β2-adrenergic receptor agonist that leads to myocardial stress and mitochondrial damage, is extensively used for in vitro and in vivo studies to test the efficacy of therapeutic strategies in heart failure (HF). This study evaluated the cell morphology, nucleotide concentrations, and mitochondrial function of ISO-treated cardiomyocytes stimulated with the activators of mitochondrial biogenesis and nucleotide precursors. H9c2 rat cardiomyocyte line cells were treated with ISO in the presence of mitochondrial biogenesis stimuli quercetin (Que), rosiglitazone (Ros), S-Nitroso-N-acetyl-DL-penicillamin (SNAP), and NAD+ precursor, nicotinamide riboside (NR). The intracellular concentrations of nucleotides were analyzed using high-performance liquid chromato-graphy, and the Seahorse metabolic flux analyzer determined the mitochondrial function. ISO decreased intracellular ATP concentration in H9c2 cells as compared to control. The treatment with SNAP increased ATP concentration compared to ISO-only treated cells, while Que, Ros, and NR had no effect. NR treatment led to the elevation of intracellular NAD+ concentration, while the treatment with SNAP, Ros, and NR stimulated the mitochondrial respiration in ISO-pretreated H9c2 cells. In conclusion, mitochondrial biogenesis activators consistently improved cardiomyocyte mitochondrial function, but only selected molecules helped to improve ATP or NAD+ concentrations. This information may help to optimize treatment to ameliorate energy imbalance in failing cardiomyocytes.

Keywords: Cardiomyocytes; biogenesis; mitochondria; nucleotides; pharmacology

DOI: https://doi.org/10.1080/15257770.2025.2453105

Am J Cardiovasc Drugs. 2025 Feb 05.

Cardiovascular Effects of Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis.

Milene Vitória Sampaio Sobral, Livia Kneipp Rodrigues, Abner Mácola Pacheco Barbosa, Naila Camila da Rocha, Isac Ribeiro Moulaz, João Pedro Pereira Dos Santos, Bruno Henrique Couto Oliveira, João Lucas de Magalhães Leal Moreira, Francis Lopes Pacagnelli, Camila Mota Guida.

BACKGROUND: Semaglutide has emerged as an effective medication for treating type 2 diabetes mellitus (DM). However, the cardiovascular effects and safety of this agent in patients with heart failure with preserved ejection fraction (HFpEF) are unclear.
OBJECTIVE: This systematic review and meta-analysis aimed to assess the clinical and laboratory effects of semaglutide compared to placebo in patients with HFpEF.
METHODS: We systematically searched EMBASE, PubMed, and Cochrane databases for randomized controlled trials (RCTs) and non-randomized cohorts, from inception to July 2024, comparing semaglutide versus placebo in patients with HFpEF. Statistical analyses were performed using R Studio 4.3.2. Mean difference (MD) and odds ratio (OR) with 95% confidence intervals (CIs) were pooled across trials.
RESULTS: This meta-analysis included three studies, two RCTs and one non-randomized cohort, reporting data on 1463 patients. The follow-up time of the studies was 52 weeks. Compared to placebo, the use of semaglutide was associated with a significant increase in the 6-min walk distance (MD 16.20; 95% CI 10.19-22.21; p < 0.01; I2 = 0%). Additionally, reductions were observed in systolic blood pressure (MD -2.22; 95% CI -3.60 to -0.83; p < 0.01; I2 = 0%), C-reactive protein level (MD 0.59; 95% CI 0.49-0.70; p < 0.01; I2 = 51%), and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels (MD 0.81; 95% CI 0.74-0.89; p < 0.01; I2 = 0%).
CONCLUSION: These findings suggest that the use of semaglutide is associated with clinical and laboratory benefits in patients with HFpEF.

DOI: https://doi.org/10.1007/s40256-025-00721-4