bims-hafaim 2024-12-08 papers

Issue of 2024–12–08
two papers selected by
Kyle McCommis, Saint Louis University

Front Pharmacol. 2024 ;15 1467132

Astragaloside IV alleviates inflammation and improves myocardial metabolism in heart failure mice with preserved ejection fraction.

Xiao Wang, Xinting Chen, Yuting Wang, Xinyu He, Lan Li, Xiaodan Wang, Yuting Huang, Guanwei Fan, Jingyu Ni.

Background: Heart failure with preserved ejection fraction (HFpEF) has grown to become the dominant form of heart failure worldwide. However, no unequivocally effective treatment for HFpEF has been identified in clinical trials. In this study, we report that Astragaloside IV (AS-IV) can be used to treat HFpEF.
Methods: Mice were fed on a high-fat diet and given 0.5 g/L L-NAME (in drinking water) for 10 weeks to establish the HFpEF model. After 10th weeks, the HFpEF mice were given 10 mg/kg empagliflozin, 10 mg/kg AS-IV, or 20 mg/kg AS-IV for 4 weeks. The echocardiography, blood pressure, hemodynamics, heart failure biomarkers, collagen deposition and fibrosis, histopathology, and inflammation in HFpEF mice were evaluated. Metabolic profiling based on NMR measurements was also performed. Myocardial glucose and fatty acid metabolism were evaluated.
Results: AS-IV improves cardiac function and myocardial remodeling in HFpEF mice. AS-IV attenuates systemic inflammatory infiltration and myocardial inflammation levels in HFpEF mice by decreasing the expression of plasma inflammatory markers GDF15, CRP, IL1RL1, and MCP-1, NLRP3, IL-1β, Caspase-1, and IL-6 in the myocardium of HFpEF mice. Metabolomic analysis suggested that AS-IV improved cardiac glucose and fatty acid metabolism in HFpEF mice. Further studies showed that AS-IV significantly improved Complex I activity, increased ATP production, and elevated plasma NAD + levels; AS-IV also significantly improved pyruvate dehydrogenase activity and decreased pyruvate and lactate accumulation, thereby improving glucose metabolism in the hearts of HFpEF mice.
Conclusion: These results provide novel evidence that Astragaloside IV alleviates inflammation and improves myocardial metabolism in HFpEF mice.

Keywords: HFpEF; astragaloside IV; inflammation; metabolism; mitochondria

DOI: https://doi.org/10.3389/fphar.2024.1467132

Epigenomics. 2024 Dec 02. 1-16

Multi-omics insights into the pathogenesis of diabetic cardiomyopathy: epigenetic and metabolic profiles.

Li Zhou, Shuai Mei, Xiaozhu Ma, Qidamugai Wuyun, Ziyang Cai, Chen Chen, Hu Ding, Jiangtao Yan.

AIM: Diabetic cardiomyopathy (DbCM), a complex metabolic disease, greatly threatens human health due to therapeutic limitations. Multi-omics approaches facilitate the elucidation of its intrinsic pathological changes.
METHODS: Metabolomics, RNA-seq, proteomics, and assay of transposase-accessible chromatin (ATAC-seq) were utilized to elucidate multidimensional molecular alterations in DbCM.
RESULTS: In the heart and plasma of mice with DbCM, metabolomic analysis demonstrated significant differences in branched-chain amino acids (BCAAs) and lipids. Subsequent RNA-seq and proteomics showed that the key genes, including BCKDHB, PPM1K, Cpt1b, Fabp4, Acadm, Acadl, Acadvl, HADH, HADHA, HADHB, Eci1, Eci2, PDK4, and HMGCS2, were aberrantly regulated, contributing to the disorder of BCAAs and fatty acids. ATAC-seq analysis underscored the pivotal role of epigenetic regulation by revealing dynamic shifts in chromatin accessibility and a robust positive correlation with gene expression patterns in diabetic cardiomyopathy mice. Furthermore, motif analysis identified that KLF15 as a critical transcription factor in DbCM, regulating the core genes implicated with BCAAs metabolism.
CONCLUSION: Our research delved into the metabolic alterations and epigenetic landscape and revealed that KLF15 may be a promising candidate for therapeutic intervention in DbCM.

Keywords: ATAC-seq; BCAAs; Diabetic cardiomyopathy; RNA-seq; epigenomics; metabolomics; multi-omics

DOI: https://doi.org/10.1080/17501911.2024.2435257