Single-cell transcriptomics identifies Col1a1 and Col1a2 as hub genes in obesity-induced cardiac fibrosis

Biochemical and Biophysical Research Communications, Journal Year: 2022, Volume and Issue: 618, P. 30 - 37

Published: June 9, 2022

Language: Английский

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Use of Statins in Heart Failure with Preserved Ejection Fraction: Current Evidence and Perspectives

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4958 - 4958

Published: May 1, 2024

Systemic inflammation and coronary microvascular endothelial dysfunction are essential pathophysiological factors in heart failure (HF) with preserved ejection fraction (HFpEF) that support the use of statins. The pleiotropic properties statins, such as anti-inflammatory, antihypertrophic, antifibrotic, antioxidant effects, generally accepted may be beneficial HF, especially HFpEF. Numerous observational clinical trials have consistently shown a prognostic effect statins patients HFpEF, while results two larger HFrEF been controversial. Such differences related to more pronounced impact on pathophysiology HFpEF pro-inflammatory comorbidities (arterial hypertension, diabetes mellitus, obesity, chronic kidney disease) common This review discusses potential mechanisms statin action for well evaluated effects left ventricular diastolic function outcomes

Language: Английский

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Myocardial dysfunction caused by MyBPC3 P459fs mutation in hypertrophic cardiomyopathy: evidence from multi-omics approaches and super-resolution imaging

Frontiers in Cardiovascular Medicine, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 27, 2025

Mutations in the sarcomere protein, particularly cardiac myosin binding protein C gene (MyBPC3), were most frequent genetic cause of hypertrophic cardiomyopathy (HCM). The pathogenic MyBPC3 P459fs mutation has been reported HCM patients. However, there was limited knowledge structure-function relationships and potential pathways clinical with mutation. We used multi-omics approaches super-resolution imaging to explore effects on humans cells. patients carrying (MyBPC3-P459fs HCMs) healthy controls (HCs) evaluated for myocardial function using both conventional advanced echocardiography. In parallel, H9C2 cells infected either (P459fs cells) or its wild type (WT investigated fiber formation behind this metabolomics proteomics. First, echocardiography showed that MyBPC3-P459fs HCMs exhibited left ventricular diastolic systolic dysfunction. Subsequently, indicated formed fewer shorter fibers cytoplasm compared WT Moreover, our metabolomic proteomic data suggested several key components mitochondrial membrane integrity, remodeling, energy metabolism, oxidative stress, inflammation, actin capacity significantly altered response This investigation dysfunction disarray added underlying this. These findings provided a link between observed structural functional disorders onset pathogenesis might have significant translational contribution effective treatment

Language: Английский

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Nicotinamide riboside kinase-2 regulates metabolic adaptation in the ischemic heart

Journal of Molecular Medicine, Journal Year: 2023, Volume and Issue: 101(3), P. 311 - 326

Published: Feb. 19, 2023

Language: Английский

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Statins and Cardiomyocyte Metabolism, Friend or Foe?

Journal of Cardiovascular Development and Disease, Journal Year: 2023, Volume and Issue: 10(10), P. 417 - 417

Published: Oct. 2, 2023

Statins inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis, and are cornerstone of lipid-lowering treatment. They significantly reduce cardiovascular morbidity mortality. However, musculoskeletal symptoms observed 7 to 29 percent all users. The mechanism underlying these complaints has become increasingly clear, but less is known about effect on cardiac muscle function. Here we discuss both adverse beneficial effects statins heart. exert pleiotropic protective diseased heart that independent their cholesterol-lowering activity, including reduction hypertrophy, fibrosis infarct size. Adverse seem be associated with altered cardiomyocyte metabolism. In this review explore differences action potential side skeletal how they present clinically. These insights may contribute a more personalized treatment strategy.

Language: Английский

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Statins for Heart Failure with Preserved Ejection Fraction: Current Evidence and Perspectives

Published: April 15, 2024

Systemic inflammation and coronary microvascular endothelial dysfunction are essential pathophysiological factors in heart failure with preserved ejection fraction (HFpEF) that support the use of statins. The pleiotropic properties statins, such as anti-inflammatory, antihypertrophic, antifibrotic, antioxidant effects, generally accepted may be beneficial HF, especially HFpEF. Numerous observational clinical trials have consistently shown a prognostic effect statins patients HFpEF, while results two larger HFrEF been controversial. Such differences related to more pronounced impact on pathophysiology HFpEF pro-inflammatory comorbidities (arterial hypertension, diabetes mellitus, obesity, chronic kidney disease) common This review discusses potential mechanisms statin action for well evaluated effects left ventricular diastolic function outcomes

Language: Английский

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A network medicine approach to study comorbidities in heart failure with preserved ejection fraction

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

Published: July 24, 2023

Comorbidities are expected to impact the pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF). However, comorbidity profiles usually reduced a few comorbid disorders. Systems medicine approaches can model phenome-wide improve our understanding HFpEF and infer associated genetic profiles.We retrospectively explored 569 comorbidities in 29,047 HF patients, including 8062 6585 (HFrEF) patients from German university hospital. We assessed differences between subtypes via multiple correspondence analysis. Then, we used machine learning classifiers identify distinctive HFrEF patients. Moreover, built network (HFnet) main disease clusters that summarized comorbidity. Lastly, predicted novel gene candidates for by linking HFnet multilayer network, integrating databases. To corroborate candidate genes, collected transcriptomic data murine model. compared genes signature as well literature.We found high degree variance HFrEF, while each was more similar HFmrEF. The present were diverse than those included neoplastic, osteologic rheumatoid Disease communities captured important concepts which could be assigned subtypes, age groups, sex. Based on profile, recovered candidates, involved fibrosis (COL3A1, LOX, SMAD9, PTHL), hypertrophy (GATA5, MYH7), oxidative stress (NOS1, GSST1, XDH), endoplasmic reticulum (ATF6). Finally, significantly overrepresented providing additional plausibility their relevance.We applied systems analyze patient cohort. able helped characterize derived distinct profile HFpEF, leveraged suggest propagation. identification routine clinical provides insights may diagnosis treatment targets

Language: Английский

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Se alleviates homocysteine‑induced fibrosis in cardiac fibroblasts via downregulation of lncRNA MEG3

Experimental and Therapeutic Medicine, Journal Year: 2021, Volume and Issue: 22(5)

Published: Sept. 7, 2021

Selenium (Se) is considered to have antioxidant properties, which are beneficial for heart condition. Hyperhomocysteinemia (HHCY) has been suggested potentially lead failure and characterized by cardiac fibrosis; however, investigation on the role of Se HHCY in fibrosis rare. Since previous studies demonstrated important long non‑coding RNA maternally expressed 3 (MEG3) some diseases, present study aimed determine how MEG3 might exert regulatory effects HCY‑induced fibroblasts (CFs). Mouse CFs were isolated treated with HCY Se. The expression α‑smooth muscle actin (α‑SMA), collagen I III was detected western blotting reflect CF fibrosis. Reverse transcription‑quantitative PCR performed levels MEG3. Inflammation oxidative stress responses analyzed measuring TNF‑α, IL‑1β (ELISA) reactive oxygen species (using a commercial kit), respectively. Cell Counting Kit‑8 used evaluate proliferation. Total phosphorylated (p) janus kinase 2 (JAK2) signal transducer activator transcription (STAT3) evaluated blotting. transfected adenovirus expressing short‑hairpin knock down expression. treatment downregulated level HCY‑stimulated CFs, whilst inhibiting inflammatory response. Furthermore, inhibited increased proliferation following treatment. In addition, MEG3‑knockdown could improve caused HCY. ratios p‑JAK2/JAK2 p‑STAT3/STAT3 decreased or silencing. Taken together, findings from that may alleviate downregulating reducing response CFs. This suggests be potential therapeutic option treating future.

Language: Английский

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Role of chaperones and endoplasmic reticulum stress in protein complexity associated with dyslipidemia: A future perspective to novel therapeutics (Review)

World Academy of Sciences Journal, Journal Year: 2023, Volume and Issue: 6(1)

Published: Dec. 6, 2023

Protein structure is extraordinarily complex and consists of various folding processes, namely, primary, secondary, tertiary quaternary. Currently, researchers are eager to acquire knowledge elucidate the mechanisms involved in these processes. Over past decade, several studies have indicated that endoplasmic reticulum stress (ERS) response assists protein via intracellular signaling. ERS plays a key role unfolding. An increase promotes unwinding folded protein. The present review specifically discusses complexity dyslipidemia (the condition elevated cholesterol levels blood) with unfolded response. achieved by pathological conditions, including oxidative stress, calcium imbalance high blood. Therefore, review, highlighted as regards complexity, which indicates considering would be great benefit reducing ERS. literature was performed using search engines web‑based databases (Google Scholar ScienceDirect) keywords such ‘Role chaperones dyslipidemia’ ‘Protein complexity’ or dyslipidemia’. Furthermore, associated ER finding novel therapeutics for disease prevention also discussed.

Language: Английский

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Methylation and transcriptomic expression profiles of HUVEC in the oxygen and glucose deprivation model and its clinical implications in AMI patients

Frontiers in Genetics, Journal Year: 2023, Volume and Issue: 14

Published: Dec. 7, 2023

The obstructed coronary artery undergoes a series of pathological changes due to ischemic-hypoxic shocks during acute myocardial infarction (AMI). However, the altered DNA methylation levels in endothelial cells under these conditions and their implication for etiopathology AMI have not been investigated detail. This study aimed explore relationship between pathologically gene expression profile human umbilical vein (HUVECs) subjected oxygen-glucose deprivation (OGD), its clinical implications patients. Illumina Infinium MethylationEPIC BeadChip assay was used genome-wide using Novaseq6000 platform mRNA sequencing 3 pairs HUVEC-OGD control samples. GO KEGG pathway enrichment analyses, as well correlation, causal inference test (CIT), protein-protein interaction (PPI) analyses identified 22 hub genes that were validated by MethylTarget qRT-PCR. ELISA detect four target molecules associated with progression AMI. A total 2,524 differentially expressed (DEGs) 22,148 methylated positions (DMPs) corresponding 6,642 (DMGs) screened (|Δβ|>0.1 detection p < 0.05). After GO, KEGG, CIT, PPI 441 filtered. qRT-PCR confirmed overexpression VEGFA, CCL2, TSP-1, SQSTM1, BCL2L11, TIMP3 genes, downregulation MYC, CD44, BDNF, GNAQ, RUNX1, ETS1, NGFR, MME, SEMA6A, GNAI1, IFIT1, MEIS1. fragments BDNF_1_ (r = 0.931, 0.0001) SQSTM1_2_NEW 0.758, 0.0043) positively correlated expressions MYC_1_ -0.8245, 0.001) negatively correlated. Furthermore, TNFSF10 BDNF elevated peripheral blood patients (p 0.0284 0.0142, respectively). Combined from vitro cellular assays samples, aiming establish potential chain factor (DNA methylation) - mediator (mRNA)-cell outcome (endothelial cell injury)-clinical (AMI), our promising OGD-specific which provided solid basis screening fundamental diagnostic prognostic biomarkers injury Moreover, it furnished first evidence ischemia hypoxia, BNDF regulated blood.

Language: Английский

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