bims-hafaim Biomed News
on Heart failure metabolism
Issue of 2022‒07‒17
six papers selected by
Kyle McCommis
Saint Louis University
  1. Cardiac-specific overexpression of Ndufs1 ameliorates cardiac dysfunction after myocardial infarction by alleviating mitochondrial dysfunction and apoptosis.
  2. Nogo-A reduces ceramide de novo biosynthesis to protect from heart failure.
  3. Effects of Glucagon-Like Peptide-1 Receptor Agonist (GLP-1RA) on Cardiac Structure and Function: A Systematic Review and Meta-Analysis of Randomized-Controlled Trials.
  4. Effects of 26-week treatment with empagliflozin versus glimepiride on myocardial glucose metabolic rate in patients with type 2 diabetes: the randomized, open-label, active-controlled crossover FIORE trial.
  5. [Coenzyme Q-10 in the treatment of patients with chronic heart failure and reduced left ventricular ejection fraction: systematic review and meta-analysis].
  6. Metformin Attenuates Cardiac Hypertrophy Via the HIF-1α/PPAR-γ Signaling Pathway in High-Fat Diet Rats.
  1. Exp Mol Med. 2022 Jul 11.
    Cardiac-specific overexpression of Ndufs1 ameliorates cardiac dysfunction after myocardial infarction by alleviating mitochondrial dysfunction and apoptosis.
    Bingchao Qi, Liqiang Song, Lang Hu, Dong Guo, Gaotong Ren, Tingwei Peng, Mingchuan Liu, Yexian Fang, Chunyu Li, Mingming Zhang, Yan Li.
      Myocardial infarction (MI) is the leading cause of premature death among adults. Cardiomyocyte death and dysfunction of the remaining viable cardiomyocytes are the main pathological factors of heart failure after MI. Mitochondrial complexes are emerging as critical mediators for the regulation of cardiomyocyte function. However, the precise roles of mitochondrial complex subunits in heart failure after MI remain unclear. Here, we show that NADH:ubiquinone oxidoreductase core subunit S1 (Ndufs1) expression is decreased in the hearts of heart failure patients and mice with myocardial infarction. Furthermore, we found that cardiac-specific Ndufs1 overexpression alleviates cardiac dysfunction and myocardial fibrosis in the healing phase of MI. Our results demonstrated that Ndufs1 overexpression alleviates MI/hypoxia-induced ROS production and ROS-related apoptosis. Moreover, upregulation of Ndufs1 expression improved the reduced activity of complex I and impaired mitochondrial respiratory function caused by MI/hypoxia. Given that mitochondrial function and cardiomyocyte apoptosis are closely related to heart failure after MI, the results of this study suggest that targeting Ndufs1 may be a potential therapeutic strategy to improve cardiac function in patients with heart failure.
    DOI:  https://doi.org/10.1038/s12276-022-00800-5
  2. Cardiovasc Res. 2022 Jul 11. pii: cvac108. [Epub ahead of print]
    Nogo-A reduces ceramide de novo biosynthesis to protect from heart failure.
    Linda Sasset, Onorina Laura Manzo, Yi Zhang, Alice Marino, Luisa Rubinelli, Maria Antonietta Riemma, Madhavi Latha S Chalasani, Dragos C Dasoveanu, Fiorentina Roviezzo, Stanislovas S Jankauskas, Gaetano Santulli, Maria Rosaria Bucci, Theresa T Lu, Annarita Di Lorenzo.
      AIMS: Growing evidence correlate the accrual of the sphingolipid ceramide in plasma and cardiac tissue with heart failure (HF). Regulation of sphingolipid metabolism in the heart and the pathological impact of its derangement remain poorly understood. Recently, we discovered that Nogo-B, a membrane protein of endoplasmic reticulum, abundant in the vascular wall, down-regulates the sphingolipid de novo biosynthesis, via serine palmitoyltransferase (SPT), first and rate liming enzyme, to impact vascular functions and blood pressure. Nogo-A, a splice isoform of Nogo, is transiently expressed in cardiomyocyte (CM) following pressure overload. Cardiac Nogo is upregulated in dilated and ischemic cardiomyopathies in animals and humans. However, its biological function in the heart remains unknown.METHODS AND RESULTS: We discovered that Nogo-A is a negative regulator of SPT activity and refrains ceramide de novo biosynthesis in CM exposed to hemodynamic stress, hence limiting ceramide accrual.At 7 days following transverse aortic constriction (TAC), SPT activity was significantly upregulated in CM lacking Nogo-A and correlated with ceramide accrual, particularly very long chain ceramides, which are the most abundant in CM, resulting in the suppression of "beneficial" autophagy. At 3 months post-TAC, mice lacking Nogo-A in CM showed worse pathological cardiac hypertrophy and dysfunction, with ca.50% mortality rate.
    CONCLUSIONS: Mechanistically, Nogo-A refrains ceramides from accrual, therefore preserves the "beneficial" autophagy, mitochondrial function, and metabolic gene expression, limiting the progression to HF under sustained stress.
    DOI:  https://doi.org/10.1093/cvr/cvac108
  3. Cardiovasc Drugs Ther. 2022 Jul 12.
    Effects of Glucagon-Like Peptide-1 Receptor Agonist (GLP-1RA) on Cardiac Structure and Function: A Systematic Review and Meta-Analysis of Randomized-Controlled Trials.
    Shi Yin Wong, Ainsley Ryan Yan Bin Lee, Aaron Hon Jiun Sia, Yu Jun Wo, Yao Hao Teo, Yao Neng Teo, Nicholas L Syn, Ching-Ching Ong, Lynette L Teo, Tiong-Cheng Yeo, Kian-Keong Poh, William K Kong, Raymond C Wong, Ching-Hui Sia.
      PURPOSE: Recent trials suggest glucagon-like peptide-1 receptor agonists (GLP-1RAs) may have a cardioprotective role by reducing major adverse cardiac events, stroke mortality and heart failure-related hospitalisations. We examined whether and how GLP-1RAs affect cardiac function in cardiovascular and metabolic diseases including type 2 diabetes, heart failure and post-myocardial infarction.METHODS: In this PRISMA-adherent systematic review and meta-analysis, three databases were searched from inception to July 2021 and registered on PROSPERO (CRD42021259661).
    RESULTS: 20 reports of 19 randomized placebo-controlled trials including 2062 participants were meta-analyzed. Among type 2 diabetes patients, GLP-1RA resulted in improved systolic function measured by circumferential strain (mean difference [MD]= -5.48; 95% CI: -10.47 to -0.49; P= 0.03; I2= 89%) and diastolic dysfunction measured by E / A (MD= -0.15; 95% CI: -0.25 to -0.05; P= 0.003; I2= 0%). For post-myocardial infarction patients, GLP-1RA reduced infarct size (g) (MD= -5.36; 95% CI: -10.68 to -0.04; P= 0.05; I2= 78%). Liraglutide, but not exenatide, demonstrated improved systolic function, by increasing left ventricular ejection fraction (MD= 4.89; 95% CI: 3.62 to 6.16; P< 0.00001; I2= 0%) and reducing left ventricular end-systolic volume (MD= -4.15; 95% CI: -7.49 to -0.81; P = 0.01; I2= 0%). Among heart failure patients, no significant changes were noted.
    CONCLUSION: GLP-1RA drugs may improve systolic and diastolic function in type 2 diabetes and reduce infarct size post-acute myocardial infarction with no demonstrable effect on cardiac function in heart failure. Tailored recommendations for the use of GLP-1RAs for cardioprotection should be considered for each patient's condition.
    Keywords:  Glucagon-like peptide-1 receptor agonists (GLP-1 RA); cardiac structure and function; myocardial infarction, heart failure; type 2 diabetes
    DOI:  https://doi.org/10.1007/s10557-022-07360-w
  4. Diabetes Obes Metab. 2022 Jul 15.
    Effects of 26-week treatment with empagliflozin versus glimepiride on myocardial glucose metabolic rate in patients with type 2 diabetes: the randomized, open-label, active-controlled crossover FIORE trial.
    Elena Succurro, Patrizia Vizza, Annalisa Papa, Sofia Miceli, Francesco Cicone, Teresa Vanessa Fiorentino, Angela Sciacqua, Francesco Andreozzi, Pierangelo Veltri, Giuseppe Lucio Cascini, Giorgio Sesti.
      AIM: The primary aim of this study was to determine whether treatment with empagliflozin was able to affect myocardial glucose metabolic rate, assessed by cardiac dynamic 18 F-FDG-PET combined with a euglycemic-hyperinsulinemic clamp compared to glimepiride in patients with type 2 diabetes.MATERIALS AND METHODS: To further investigate the cardioprotective mechanism of SGLT2i we performed a 26-week, randomized, open-label, cross-over, active-comparator study to determine the effects of empagliflozin 10 mg versus glimepiride 2 mg daily on myocardial glucose metabolic rate assessed by cardiac dynamic 18 F-FDG-PET combined with a euglycemic-hyperinsulinemic clamp in 23 patients with type 2 diabetes. We also measured cardiac geometry, myocardial mechano-energetic efficiency, and systolic and diastolic function by echocardiography.
    RESULTS: As compared with glimepiride, treatment with empagliflozin resulted in a greater reduction in myocardial glucose metabolic rate from baseline to 26 weeks (adjusted difference -6.07 μmol/min/100g, (-8.59, -3.55), P<0.0001). Moreover, empagliflozin led to significant reductions in left atrial diameter, left ventricular end-systolic and end-diastolic volumes, NT-proBNP levels, blood pressure, heart rate, stroke work, myocardial oxygen consumption, estimated by rate pressure product, and an increase in ejection fraction, myocardial mechano-energetic efficiency, red blood cells, hematocrit, and hemoglobin levels compared to glimepiride.
    CONCLUSIONS: The present study provides evidence that empagliflozin treatment in subjects with type 2 diabetes without coronary artery disease leads to a significant reduction in myocardial glucose metabolic rate. This article is protected by copyright. All rights reserved.
    DOI:  https://doi.org/10.1111/dom.14816
  5. Kardiologiia. 2022 Jun 30. 62(6): 3-14
    [Coenzyme Q-10 in the treatment of patients with chronic heart failure and reduced left ventricular ejection fraction: systematic review and meta-analysis].
    V Yu Mareev, Yu V Mareev, Yu L Begrambekova.
      Aim    The aim of the study was evaluation of the effect of the coenzyme Q10 (Q10) treatment on all-cause and cardiovascular mortality of patients with chronic heart failure (CHF). Q-10 increases the electron transfer in the mitochondrial respiratory chain and exerts anti-inflammatory and antioxidant effects. These effects improve the endothelial function and reduce afterload, which facilitates the heart pumping function. Patients with reduced left ventricular (LV) ejection fraction (EF) (CHFrEF) have low Q10.Material and methods    Criteria of inclusion in the meta-analysis: 1) placebo-controlled studies; 2) enrollment of at least 100 patients; 3) publications after 2010, which implies an optimal basic therapy for CHF; 4) duration of at least 6 months; 5) reported cardiovascular and/or all-cause mortality; 6) using sufficient doses of Q10 (&gt;100 mg/day). The search was performed in CENTRAL, MEDLINE, Embase, Web of Science, E-library, and ClinicalTrials.gov databases. All-cause mortality was the primary efficacy endpoint in this systematic review and the meta-analysis. The secondary endpoint was cardiovascular mortality. Meta-analysis was performed according to the Mantel-Haenszel methods. The Cochrane criterion (I2) was used for evaluation of statistical heterogeneity. The random effects model was used at I2≥50 %, whereas the fixed effects model was used at I2&lt;50.Results    Analysis of studies published from 01.01.2011 to 01.12.2021 identified 357 publications, 23 of which corresponded to the study topic, but only 6 (providing results of four randomized clinical trials, RCT) completely met the predefined criteria. The final analysis included results of managing 1139 patients (586 received Q10 and 553 received placebo). Risk of all-cause death was analyzed by data of four RCTs (1139 patients). The decrease in the risk associated with the Q10 treatment was 36 % (OR=0.64, 95 % CI 0.48-0.87, р=0.004). The heterogeneity of studies was low (Chi2=0.84; p=0.84; I2=0 %). Risk of cardiovascular mortality was analyzed by data of two RCTs (863 patients). The decrease in the risk associated with the Q10 treatment was significant, 55% (OR=0.45, 95 % CI: 0.32-0.64, р=0.00001). In this case, the data heterogeneity was also low (Chi2=0.41; p=0.52; I2=0 %).Conclusion    The meta-analysis confirmed the beneficial effect of coenzyme Q10 on the prognosis of patients with CHFrEF receiving the recommended basic therapy.
    DOI:  https://doi.org/10.18087/cardio.2022.6.n2050
  6. Front Pharmacol. 2022 ;13 919202
    Metformin Attenuates Cardiac Hypertrophy Via the HIF-1α/PPAR-γ Signaling Pathway in High-Fat Diet Rats.
    Yuansheng Liu, Qian Zhang, Lei Yang, Wencong Tian, Yinan Yang, Yuhang Xie, Jing Li, Liang Yang, Yang Gao, Yang Xu, Jie Liu, Yachen Wang, Jie Yan, Guoxun Li, Yanna Shen, Zhi Qi.
      Coronary artery disease (CAD) and cardiac hypertrophy (CH) are two main causes of ischemic heart disease. Acute CAD may lead to left ventricular hypertrophy (LVH). Long-term and sustained CH is harmful and can gradually develop into cardiac insufficiency and heart failure. It is known that metformin (Met) can alleviate CH; however, the molecular mechanism is not fully understood. Herein, we used high-fat diet (HFD) rats and H9c2 cells to induce CH and clarify the potential mechanism of Met on CH. We found that Met treatment significantly decreased the cardiomyocyte size, reduced lactate dehydrogenase (LDH) release, and downregulated the expressions of hypertrophy markers ANP, VEGF-A, and GLUT1 either in vivo or in vitro. Meanwhile, the protein levels of HIF-1α and PPAR-γ were both decreased after Met treatment, and administrations of their agonists, deferoxamine (DFO) or rosiglitazone (Ros), markedly abolished the protective effect of Met on CH. In addition, DFO treatment upregulated the expression of PPAR-γ, whereas Ros treatment did not affect the expression of HIF-1α. In conclusion, Met attenuates CH via the HIF-1α/PPAR-γ signaling pathway.
    Keywords:  HIF-1α; PPAR-γ; cardiac hypertrophy; coronary artery disease; high-fat diet; metformin
    DOI:  https://doi.org/10.3389/fphar.2022.919202
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