Effects of sex and obesity on immune checkpoint inhibition-related cardiac systolic dysfunction in aged mice DOI Creative Commons
Nabil V. Sayour, Dániel Kucsera,

Abdulaziz AlHaddad

и другие.

Basic Research in Cardiology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 8, 2024

Despite accumulating data on underlying mechanisms, the influence of sex and prevalent cardio-metabolic co-morbidities manifestation severity immune checkpoint inhibitor (ICI)-induced cardiotoxicity has not been well defined. To elucidate whether affect ICI-induced cardiotoxicity, we randomized 17-month-old male female mice to receive control diet (CON) or high-fat (HFD) + L-NAME-a well-established mouse model co-morbidities-for 17 weeks (n = 5-7), evaluated markers T-cell function in spleen. As expected, HFD L-NAME significantly increased body- heart weight, serum cholesterol levels, caused no systolic dysfunction, however, led diastolic cardiomyocyte hypertrophy, fibrosis only males compared corresponding CON. Western blot analyses splenic protein levels showed differential expression depending co-morbidities, suggesting exhaustion both sexes L-NAME, but more pronounced males. In a sub-study with similar setup, tested cardiotoxic manifestations ICI by treating anti-PD-1 monoclonal antibody (ICI) for last 2 administration 5-7). After treatment, cardiac functions decreased CON, groups baseline (before administration). conclusion, this exploratory study using aged mice, describe first time that ICI-related dysfunction is diminished when obesity hypercholesterolemia are present, possibly due obesity-related exhaustion.

Язык: Английский

The Prognostic Value of the Triglyceride Glucose Index in Patients With Acute Myocardial Infarction DOI Creative Commons
Hao Qian, Yuanyuan Zhao, Lijuan Chen

и другие.

Journal of Cardiovascular Pharmacology and Therapeutics, Год журнала: 2023, Номер 28

Опубликована: Янв. 1, 2023

Objective: The triglyceride-glucose (TyG) index is a simple and reliable surrogate for insulin resistance. Recent studies have suggested that the TyG an independent predictor of cardiovascular disease. However, prognostic value in patients with acute myocardial infarction (AMI) remains uncertain. Thus, this study aimed to evaluate AMI. Methods: AMI admitted Zhongda Hospital from 2018 2020 were successively enrolled. After screening inclusion criteria, 1144 divided into three groups according tertiles distribution. Patients followed up 1 year as outpatients or contacted via telephone, occurrence timing all-cause deaths recorded. Results: was significantly correlated heart failure (HF) patients. high (group 3) (odds ratio: 9.070, 95% confidence interval [CI] 4.359-18.875, P＜.001) had higher incidence HF compared median 2). Similarly, death group 3 than 2 during 1-year follow-up (hazard 2.996, CI 1.058-8.487, P = .039). Conclusion: closely related may be valuable indicator predict long-term prognosis

Язык: Английский

Процитировано

14
Metabolic reprogramming and interventions in angiogenesis DOI Creative Commons
Yun Liu, Zifang Wu, Yikun Li

и другие.

Journal of Advanced Research, Год журнала: 2024, Номер unknown

Опубликована: Май 1, 2024

Endothelial cell (EC) metabolism plays a crucial role in the process of angiogenesis. Intrinsic metabolic events such as glycolysis, fatty acid oxidation, and glutamine metabolism, secure vascular migration proliferation, energy biomass production, well redox homeostasis maintenance during vessel formation. Nevertheless, perturbation EC instigates dysregulation-associated diseases, especially cancer. In this review, we aim to discuss regulation angiogenesis by metabolites enzymes, prospect possible therapeutic opportunities strategies targeting metabolism. work, various aspects considering normal diseased vasculature. Of relevance, highlight that implications metabolism-targeted intervention (chiefly enzymes or metabolites) could be harnessed orchestrating spectrum pathological angiogenesis-associated diseases.

Язык: Английский

Процитировано

6
Single-cell transcriptomics reveal distinctive patterns of fibroblast activation in heart failure with preserved ejection fraction DOI Creative Commons
Jan D. Lanzer, Laura M. Wienecke, Ricardo O. Ramirez Flores

и другие.

Basic Research in Cardiology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 23, 2024

Inflammation, fibrosis and metabolic stress critically promote heart failure with preserved ejection fraction (HFpEF). Exposure to high-fat diet nitric oxide synthase inhibitor N[w]-nitro-l-arginine methyl ester (L-NAME) recapitulate features of HFpEF in mice. To identify disease-specific traits during adverse remodeling, we profiled interstitial cells early murine using single-cell RNAseq (scRNAseq). Diastolic dysfunction perivascular were accompanied by an activation cardiac fibroblast macrophage subsets. Integration fibroblasts from two models for reduced (HFrEF) identified a catalog conserved phenotypes across mouse models. Moreover, HFpEF-specific characteristics included induced metabolic, hypoxic inflammatory transcription factors pathways, including enhanced expression Angiopoietin-like 4 (Angptl4) next basement membrane compounds, such as collagen IV (Col4a1). Fibroblast was further dissected into transcriptional compositional shifts thereby highly responsive cell states each HF model identified. In contrast HFrEF, where myofibroblast matrifibrocyte crucial features, found that these played subsidiary role HFpEF. These signatures corroborated human myocardial bulk transcriptomes. Furthermore, potential cross-talk between macrophages via SPP1 TNFɑ estimated target genes Col4a1 Angptl4. Treatment recombinant ANGPTL4 ameliorated the phenotype diastolic reducing deposition vivo vitro. line, ANGPTL4, elevated plasma samples patients particularly high levels associated global-longitudinal strain. Taken together, our study provides comprehensive characterization molecular patterns HFpEF, well identification central mechanistic regulator protective effects.

Язык: Английский

Процитировано

6
Why is endothelial resilience key to maintain cardiac health? DOI Creative Commons
Lukas Tombor, Stefanie Dimmeler

Basic Research in Cardiology, Год журнала: 2022, Номер 117(1)

Опубликована: Июль 14, 2022

Abstract Myocardial injury as induced by myocardial infarction results in tissue ischemia, which critically incepts cardiomyocyte death. Endothelial cells play a crucial role restoring oxygen and nutrient supply to the heart. Latest advances single-cell multi-omics, together with genetic lineage tracing, reveal transcriptional phenotypical adaptation injured microenvironment, includes alterations metabolic, mesenchymal, hematopoietic pro-inflammatory signatures. The extent of transition mesenchymal or cell lineages is still debated, but it clear that several adaptive changes are transient endothelial revert back naïve state after resolution responses. This resilience acute stress responses important for preventing chronic dysfunction. Here, we summarize how adjust this dynamic response contributes repair regeneration. We will highlight intrinsic microenvironmental factors contribute may be targetable maintain functionally active, healthy microcirculation.

Язык: Английский

Процитировано

22
Multi-omic analysis of the cardiac cellulome defines a vascular contribution to cardiac diastolic dysfunction in obese female mice DOI Creative Commons
Malathi S.I. Dona, Ian C. Hsu,

Alex Meuth

и другие.

Basic Research in Cardiology, Год журнала: 2023, Номер 118(1)

Опубликована: Март 29, 2023

Coronary microvascular dysfunction (CMD) is associated with cardiac and predictive of mortality in obesity, especially females. Clinical data further support that CMD associates development heart failure preserved ejection fraction mineralocorticoid receptor (MR) antagonism may be more efficacious obese female, versus male, HFpEF patients. Accordingly, we examined the impact smooth muscle cell (SMC)-specific MR deletion on obesity-associated coronary diastolic female mice. Obesity was induced mice via western diet (WD) feeding alongside littermates fed standard diet. Global blockade spironolactone prevented females specific SMC-MR sufficient to prevent dysfunction. Cardiac gene expression profiling suggested reduced inflammation WD-fed independent blood pressure, aortic stiffening, hypertrophy. Further mechanistic studies utilizing single-cell RNA sequencing non-cardiomyocyte populations revealed novel impacts cellulome Specifically, WD inflammatory signatures non-myocyte including B/T cells, macrophages, endothelium as well increased VCAM-1 protein expression, fibrosis, by deletion. Further, a basal reduction mast cells WD-induced pro-inflammatory chemokine leukocyte recruitment. These reveal central role for signaling dysfunction, thus supporting emerging paradigm vascular origin obesity.

Язык: Английский

Процитировано

12
Protein–protein interaction network-based integration of GWAS and functional data for blood pressure regulation analysis DOI Creative Commons
Evridiki-Pandora Tsare, Maria I. Klapa, Nicholas Κ. Moschonas

и другие.

Human Genomics, Год журнала: 2024, Номер 18(1)

Опубликована: Фев. 8, 2024

Abstract Background It is valuable to analyze the genome-wide association studies (GWAS) data for a complex disease phenotype in context of protein–protein interaction (PPI) network, as related pathophysiology results from function interacting polyprotein pathways. The analysis may include design and curation phenotype-specific GWAS meta-database incorporating genotypic eQTL linking PPI other biological datasets, development systematic workflows network-based integration toward protein pathway prioritization. Here, we pursued this blood pressure (BP) regulation. Methods relational scheme implemented Microsoft SQL Server BP-GWAS enabled combined storage of: attributes mined Catalog literature, Ensembl-defined SNP-transcript associations, GTEx data. BP-protein interactome was reconstructed PICKLE meta-database, extending GWAS-deduced network with shortest paths connecting all GWAS-proteins into one component. shortest-path intermediates were considered BP-related. For prioritization, new integrated GWAS-based scoring two criteria: considering role by (RbSP) novel promoting common neighbors GWAS-prioritized proteins. Prioritized proteins ranked number satisfied criteria. Results includes 6687 variants linked 1167 BP-associated protein-coding genes. 1065 proteins, 672 forming connected RbSP contains 1443 additional, network-deduced indicated that essentially are at most second neighbors. prioritized set derived union BP-significant any or included 335 ~ 2/3 deduced BP extension 126 least ESR1 only satisfying three criteria, followed top-10 INSR, PTN11, CDK6, CSK, NOS3, SH2B3, ATP2B1, FES FINC, two. Pathway revealed numerous bioprocesses, which indeed functionally supported BP-associated, our understanding about Conclusions workflow could be used multifactorial diseases.

Язык: Английский

Процитировано

5
High-resolution DNA methylation changes reveal biomarkers of heart failure with preserved ejection fraction versus reduced ejection fraction DOI
Giuditta Benincasa, Mark E. Pepin, Vincenzo Russo

и другие.

Basic Research in Cardiology, Год журнала: 2024, Номер unknown

Опубликована: Дек. 27, 2024

Язык: Английский

Процитировано

5
The beneficial health effects of puerarin in the treatment of cardiovascular diseases: from mechanisms to therapeutics DOI
Qiang Wan, Qiwen Lu, Sang Luo

и другие.

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2024, Номер 397(10), С. 7273 - 7296

Опубликована: Май 6, 2024

Язык: Английский

Процитировано

4
Shensong yangxin, a multi-functional traditional Chinese medicine for arrhythmia: A review of components, pharmacological mechanisms, and clinical applications DOI Creative Commons
Xuan Lu, Tongxing Wang, Bin Hou

и другие.

Heliyon, Год журнала: 2024, Номер 10(16), С. e35560 - e35560

Опубликована: Авг. 1, 2024

As a common cardiovascular disease (CVD), Arrhythmia refers to any abnormality in the origin, frequency, rhythm, conduction velocity, timing, pathway, sequence, or other aspect of cardiac impulses, and it is one diseases clinical practice. At present, various ion channel blockers are used for treatment arrhythmia that include Na

Язык: Английский

Процитировано

4
Diversity of cells and signals in the cardiovascular system DOI Creative Commons
Eleonora Grandi, Manuel F. Navedo, Jeffrey J. Saucerman

и другие.

The Journal of Physiology, Год журнала: 2023, Номер 601(13), С. 2547 - 2592

Опубликована: Фев. 6, 2023

This white paper is the outcome of seventh UC Davis Cardiovascular Research Symposium on Systems Approach to Understanding Disease and Arrhythmia. biannual meeting aims bring together leading experts in subfields cardiovascular biomedicine focus topics importance field. The theme 2022 was 'Cell Diversity System, cell-autonomous cell-cell signalling'. Experts field contributed their experimental mathematical modelling perspectives discussed emerging questions, controversies, challenges examining cell signal diversity, co-ordination interrelationships involved function. originates from formal presentations informal discussions Symposium, which aimed develop a holistic view how multiple types system integrate influence function, disease progression therapeutic strategies. first section describes major (e.g. cardiomyocytes, vascular smooth muscle endothelial cells, fibroblasts, neurons, immune etc.) signals second emphasizes complexity at subcellular, cellular levels context development, ageing disease. Finally, third surveys technological innovations that allow interrogation this diversity advancing our understanding integrated function dysfunction.

Язык: Английский

Процитировано

9