Critical Appraisal of Pharmaceutical Therapy in Diabetic Cardiomyopathy—Challenges and Prospectives DOI Creative Commons
Elina Khattab,

Michaelia Kyriakou,

Elena Leonidou

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(1), P. 134 - 134

Published: Jan. 20, 2025

Diabetes mellitus (DM) is a multifaceted disorder with pandemic spread and remarkable burden of cardiovascular mortality morbidity. Diabetic cardiomyopathy (DBCM) has been increasingly recognized as the development cardiac dysfunction, which accompanied by heart failure (HF) symptoms in absence obvious reasons like ischemic disease, hypertension, or valvulopathies. Several pathophysiological mechanisms have proposed, including metabolic disorders (e.g., glycation products), oxidative stress, low-grade inflammation, mitochondrial etc., should guide new therapeutic strategies. Up to now, HF treatment not differed between patients without diabetes, limits expected benefits despite high risk former group. However, DBCM may require different management, prioritize anti-diabetic medications testing other novel therapies. This review aims appraise challenges prospectives individualized pharmaceutical therapy for DBCM.

Language: Английский

Obesity cardiomyopathy: evidence, mechanisms, and therapeutic implications DOI
Jun Ren, Ne N. Wu, Shuyi Wang

et al.

Physiological Reviews, Journal Year: 2021, Volume and Issue: 101(4), P. 1745 - 1807

Published: May 5, 2021

The prevalence of heart failure is on the rise and imposes a major health threat, in part, due to rapidly increased overweight obesity. To this point, epidemiological, clinical, experimental evidence supports existence unique disease entity termed "obesity cardiomyopathy," which develops independent hypertension, coronary disease, other diseases. Our contemporary review evaluates for pathological condition, examines putative responsible mechanisms, discusses therapeutic options disorder. Clinical findings have consolidated presence left ventricular dysfunction Experimental investigations uncovered pathophysiological changes myocardial structure function genetically predisposed diet-induced Indeed, consolidates wide array cellular molecular mechanisms underlying etiology obesity cardiomyopathy including adipose tissue dysfunction, systemic inflammation, metabolic disturbances (insulin resistance, abnormal glucose transport, spillover free fatty acids, lipotoxicity, amino acid derangement), altered intracellular especially mitochondrial Ca2+ homeostasis, oxidative stress, autophagy/mitophagy defect, fibrosis, dampened flow reserve, microvascular (microangiopathy), endothelial impairment. Given important role risk failure, that with preserved systolic recent rises COVID-19-associated cardiovascular mortality, should provide compelling cardiomyopathy, various comorbid conditions, offer new insights into potential approaches (pharmacological lifestyle modification) clinical management cardiomyopathy.

Language: Английский

Citations

258
Role of mitochondrial metabolic disorder and immune infiltration in diabetic cardiomyopathy: new insights from bioinformatics analysis DOI Creative Commons
Cheng Peng, Yanxiu Zhang,

Xueyan Lang

et al.

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Feb. 1, 2023

Diabetic cardiomyopathy (DCM) is one of the common cardiovascular complications diabetes and a leading cause death in diabetic patients. Mitochondrial metabolism immune-inflammation are key for DCM pathogenesis, but their crosstalk remains an open issue. This study explored separate roles mitochondrial immune microenvironment with bioinformatics.DCM chip data (GSE4745, GSE5606, GSE6880) were obtained from NCBI GEO, while gene downloaded MitoCarta3.0 database. Differentially expressed genes (DEGs) screened by GEO2R processed GSEA, GO KEGG pathway analyses. Mitochondria-related DEGs (MitoDEGs) obtained. A PPI network was constructed, hub MitoDEGs closely linked to or heart failure identified CytoHubba, MCODE CTD scores. Transcription factors target miRNAs predicted Cytoscape miRWalk database, respectively, regulatory established. The infiltration pattern analyzed ImmuCellAI, relationship between abundance investigated using Spearman method. rat model established validate expression cardiac function.MitoDEGs significantly enriched pathways involved metabolism, immunoregulation, collagen synthesis. Nine Immune analysis revealed increased B cells decreased DCs DCM. demonstrated that positively associated pro-inflammatory cells, negatively anti-inflammatory cells. In animal experiment, 4 (Pdk4, Hmgcs2, Decr1, Ivd) showed trend consistent bioinformatics result. Additionally, up-regulation Pdk4, Decr1 down-regulation Ivd distinctly reduced function.This unraveled interaction DCM, providing new insights into research on potential pathogenesis exploration novel targets medical interventions.

Language: Английский

Citations

62
Inhibition of fatty acid uptake by TGR5 prevents diabetic cardiomyopathy DOI Creative Commons
H J Wang, Jiaxing Wang, Hao Cui

et al.

Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(6), P. 1161 - 1177

Published: May 2, 2024

Language: Английский

Citations

26
FGF-based drug discovery: advances and challenges DOI
Gaozhi Chen, Lingfeng Chen, Xiaokun Li

et al.

Nature Reviews Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Language: Английский

Citations

4
CD74 ablation rescues type 2 diabetes mellitus-induced cardiac remodeling and contractile dysfunction through pyroptosis-evoked regulation of ferroptosis DOI
Lin Chen, Zhiqiang Yin,

Xing Qin

et al.

Pharmacological Research, Journal Year: 2022, Volume and Issue: 176, P. 106086 - 106086

Published: Jan. 13, 2022

Language: Английский

Citations

46
Heart failure with preserved ejection fraction (HFpEF) in type 2 diabetes mellitus: from pathophysiology to therapeutics DOI Creative Commons
Miyesaier Abudureyimu,

Xuanming Luo,

Xiang Wang

et al.

Journal of Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 14(5)

Published: April 29, 2022

Type 2 diabetes mellitus (T2DM or T2D) is a devastating metabolic abnormality featured by insulin resistance, hyperglycemia, and hyperlipidemia. T2D provokes unique changes compromises cardiovascular geometry function. Meanwhile, increases the overall risk for heart failure (HF) acts independent of classical factors including coronary artery disease, hypertension, valvular diseases. The incidence HF extremely high in patients with manifested as preserved, reduced, midrange ejection fraction (HFpEF, HFrEF, HFmrEF, respectively), all which significantly worsen prognosis T2D. HFpEF seen approximately half cases defined heterogenous syndrome discrete phenotypes, particularly close association syndrome. Nonetheless, management remains unclear, largely due to poorly pathophysiology behind HFpEF. Here, this review, we will summarize findings from multiple preclinical clinical studies well recent trials, mainly focusing on pathophysiology, potential mechanisms, therapies

Language: Английский

Citations

40
Common mechanisms underlying diabetic vascular complications: focus on the interaction of metabolic disorders, immuno-inflammation, and endothelial dysfunction DOI Creative Commons
Chongxiang Xue, Keyu Chen, Zezheng Gao

et al.

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Oct. 30, 2023

Abstract Diabetic vascular complications (DVCs), including macro- and micro- angiopathy, account for a high percentage of mortality in patients with diabetes mellitus (DM). Endothelial dysfunction is the initial role step pathogenesis DVCs. Hyperglycemia lipid metabolism disorders contribute to endothelial via direct injury products, crosstalk between immunity inflammation, as well related interaction network. Although physiological phenotypic differences support their specified changes different targeted organs, there are still several common mechanisms underlying Also, inhibitors these may decrease incidence DVCs effectively. Thus, this review provide new insights into possible measures secondary prevention DM. And we discussed current limitations those present preventive research.

Language: Английский

Citations

38
Exploring the impact of the PNPLA3 I148M variant on primary human hepatic stellate cells using 3D extracellular matrix models DOI Creative Commons
Elisabetta Caon, María Manuela Martins, Harry Hodgetts

et al.

Journal of Hepatology, Journal Year: 2024, Volume and Issue: 80(6), P. 941 - 956

Published: Feb. 15, 2024

Background and aims The PNPLA3 rs738409 C>G (encoding for I148M) variant is a risk locus the fibrogenic progression of chronic liver diseases, process driven by hepatic stellate cells (HSCs). We investigated how I148M affects HSCs biology using transcriptomic data validated findings in 3D-culture models. Methods RNA sequencing was performed on 2D-cultured primary human biopsies obese individuals, genotyped variant. Data were wild type (WT) or carrying I148M-PNPLA3 cultured 3D extracellular matrix (ECM) scaffolds from healthy cirrhotic with/without TGFB1 Cytosporone-B (Csn-B) treatment. Results Comparison between analysis highlighted shared I148M-driven dysregulated pathways related to mitochondrial function, antioxidant response, ECM remodelling signalling. Analogous WT/I148M-PNPLA3 scaffolds. Mitochondrial dysfunction linked respiratory chain complex IV insufficiency. Antioxidant capacity lower HSCs, while ROS secretion increased higher bioengineered versus signalling pathway followed same trend. In cells, TGFB1-endogenous inhibitor NR4A1 expression activation decreased: treatment with Csn-B agonist total but not regulation TGFB1/Csn-B Akt WT-PNPLA3 Erk HSCs. Conclusion have impaired dampening antifibrotic activity. These features are exacerbated ECM, highlighting dual impact fibrotic microenvironment progressive diseases. Impact implications Hepatic (HSCs) play key role associated disease. genetic mutation has been fibrogenesis, its needs further investigation. Here, comparative novel vitro model, we demonstrate cell behaviour, show that it cell's function as well gene NR4A1. Our publicly available data, platform our could facilitate discovery targets develop more effective treatments

Language: Английский

Citations

17
Nuclear receptor subfamily 4 group A member 1 promotes myocardial ischemia/reperfusion injury through inducing mitochondrial fission factor-mediated mitochondrial fragmentation and inhibiting FUN14 domain containing 1-depedent mitophagy DOI Creative Commons
Junyan Wang,

Haowen Zhuang,

Lianqun Jia

et al.

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(11), P. 4458 - 4475

Published: Jan. 1, 2024

This study investigated the mechanism by which NR4A1 regulates mitochondrial fission factor (Mff)-related and FUN14 domain 1 (FUNDC1)-mediated mitophagy following cardiac ischemia-reperfusion injury(I/R). Our findings showed that damage regulation was positively correlated with pathological pan-apoptosis of myocardial cell mitochondria. Compared wild-type mice (WT), NR4A1-knockout exhibited resistance to injury fission, characterized activation. Results increased expression level, activating mediated Mff restoring phenotype FUNDC1. The inactivation FUNDC1 phosphorylation could not mediate normalization in a timely manner, leading an excessive stress response unfolded proteins imbalance homeostasis. process disrupted quality control network, accumulation damaged mitochondria activation pan-apoptotic programs. data indicate is novel critical target I/R exertsand negative regulatory effects Mff-mediated mito-fission inhibiting FUNDC1-mediated mitophagy. Targeting crosstalk balance between NR4A1-Mff-FUNDC1 potential approach for treating I/R.

Language: Английский

Citations

17
FGF1 alleviates polystyrene nanoplastics-induced neuroinflammation through the suppression of lipophagy DOI
Bo Qian,

Chen-Qiang Wang,

Zou Su

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 302, P. 140531 - 140531

Published: Jan. 30, 2025

Language: Английский

Citations

1