Targeting Lactic Acid Modification in Ischemic Heart Diseases: Novel Therapeutics and Mechanism

Journal of Cardiovascular Translational Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

Language: Английский

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Fibrosis-Related Gene and Protein Expression in Normal and Glaucomatous Trabecular Meshwork Cells

Investigative Ophthalmology & Visual Science, Journal Year: 2025, Volume and Issue: 66(3), P. 48 - 48

Published: March 24, 2025

Purpose: Glaucomatous trabecular meshwork (GTM) tissue is characterized by excess fibrotic-like extracellular matrices, which negatively impacts aqueous humor outflow. Endothelial-to-mesenchymal transition (EndMT) the process tissues develop fibrosis. In this study, we investigated fibrotic-related gene and protein profiles of non-glaucomatous (NTM) GTM cells. Methods: Primary cells were cultured from NTM (n = 6) 5) age-matched cadaver eyes. RNA was harvested mRNA profiling 750 genes performed using human fibrosis panel (NanoString). Quantitative PCR (qPCR), Western blotting, immunofluorescence microscopy performed. A matrix metalloproteinase (MMP) fluorogenic assay used to quantitate enzyme activity. Results: Classic EndMT biomarkers, α-SMA, SNAI2, TWIST1, TWIST2, VIM, upregulated in cells, whereas increased phosphorylated SMAD2-3 indicated TGFβ signaling. had deposition FN-EDA fibronectin fibrils, but reduced amounts FN-EDB altered immunostaining active α5β1 αvβ3 integrins. NanoString analysis showed that 2 28 downregulated compared with immunoblotting confirmed levels N-cadherin decreased MMP2, CHI3L1, COL6A3, SERPINF1 proteins Whereas MMP2 reduced, there MMP Conclusions: Increased expression FN-EDA, N-cadherin, TWISTs, signaling, activity are consistent acquiring an phenotype. combination studies, a useful vitro model for studying fibrotic glaucoma.

Language: Английский

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Asprosin induces vascular endothelial-to-mesenchymal transition in diabetic lower extremity peripheral artery disease

Cardiovascular Diabetology, Journal Year: 2022, Volume and Issue: 21(1)

Published: Feb. 15, 2022

Abstract Background Altered adipokine secretion in dysfunctional adipose tissue facilitates the development of atherosclerotic diseases including lower extremity peripheral artery disease (PAD). Asprosin is a recently identified and displays potent regulatory role metabolism, but relationship between asprosin PAD remains uninvestigated. Methods 33 type 2 diabetes mellitus (T2DM) patients (DM), 51 T2DM with (DM + PAD) 30 healthy normal control (NC) volunteers were recruited blood samples collected for detecting circulatory level metabolomic screening. RNA sequencing was performed using aorta tissues from diabetic db/db mice human umbilical vein endothelial cells (HUVECs) treated to determine its impact on endothelial-to-mesenchymal transition (EndMT). Results The circulating levels DM group significantly higher than that NC group. Circulating remarkably negatively correlated ankle-brachial index (ABI), even after adjusting age, sex, body mass (BMI) other traditional risk factors PAD. Logistic regression analysis revealed an independent factor receiver-operator characteristic (ROC) curve determined good sensitivity (74.5%) specificity (74.6%) distinguish Data metabolomics displayed typical characteristics de novo amino acid synthesis collagen protein production by myofibroblasts activation TGF-β signaling pathway appeared aortic mice. directly induces EndMT HUVECs TGF-β-dependent manner as inhibitor SB431542 erased promotional effect EndMT. Conclusions Elevated might serve diagnostic marker. Mechanistically, participates vascular injury via pathway. Trial registration This trial registered at clinicaltrials.gov NCT05068895

Language: Английский

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Phloretin ameliorates diabetes-induced endothelial injury through AMPK-dependent anti-EndMT pathway

Pharmacological Research, Journal Year: 2022, Volume and Issue: 179, P. 106205 - 106205

Published: April 4, 2022

Language: Английский

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Endothelial-to-mesenchymal transition: An underappreciated mediator of diabetic complications

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

Published: Jan. 27, 2023

Diabetes and its complications represent a great burden on the global healthcare system. Diabetic are fundamentally diseases of vasculature, with endothelial cells being centerpiece early hyperglycemia-induced changes. Endothelial-to-mesenchymal transition is tightly regulated process that results in losing characteristics developing mesenchymal traits. Although endothelial-to-mesenchymal has been found to occur within most major diabetes, it not focus study or common target treatment prevention diabetic complications. In this review we summarize importance each complication, examine specific mechanisms at play, highlight potential prevent chronic diabetes.

Language: Английский

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Molecular mechanisms of endothelial remodeling under doxorubicin treatment

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 162, P. 114576 - 114576

Published: March 28, 2023

Doxorubicin (DOX) is an effective antineoplastic agent used to treat various types of cancers. However, its use limited by the development cardiotoxicity, which may result in heart failure. The exact mechanisms underlying DOX-induced cardiotoxicity are not fully understood, but recent studies have shown that endothelial-mesenchymal transition (EndMT) and endothelial damage play a crucial role this process. EndMT biological process cells lose their characteristics transform into mesenchymal cells, fibroblast-like phenotype. This has been contribute tissue fibrosis remodeling diseases, including cancer cardiovascular diseases. demonstrated increase expression markers, suggesting critical condition. Furthermore, cause damage, leading disruption barrier function increased vascular permeability. can leakage plasma proteins, edema inflammation. Moreover, DOX impair production nitric oxide, endothelin-1, neuregulin, thrombomodulin, thromboxane B2 etc. vasoconstriction, thrombosis further impairing cardiac function. In regard, review devoted generalization structuring information about known molecular under action DOX.

Language: Английский

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Mechanistic insights into the development of severe fetal growth restriction

Clinical Science, Journal Year: 2023, Volume and Issue: 137(8), P. 679 - 695

Published: April 1, 2023

Abstract Fetal growth restriction (FGR), which most commonly results from suboptimal placental function, substantially increases risks for adverse perinatal and long-term outcomes. The only “treatment” that exists is delivery, averts stillbirth but does not improve outcomes in survivors. Furthermore, the potential consequences of FGR to fetus, including cardiometabolic disorders, predispose these individuals developing their future pregnancies. This creates a multi-generational cascade effects stemming single dysfunctional placenta, understanding mechanisms underlying placental-mediated critically important if we are overall health. behind remain unknown. However, insufficiency derived maldevelopment vascular systems common etiology. To highlight mechanistic interactions within focus on development setting FGR. We delve into fetoplacental angiogenesis, robust ongoing process normal pregnancies impaired severe review cellular models FGR, with special attention novel integrin-extracellular matrix regulate angiogenesis In total, this focuses key developmental processes, specific human an underexplored area research.

Language: Английский

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Endothelial Reprogramming in Atherosclerosis

Bioengineering, Journal Year: 2024, Volume and Issue: 11(4), P. 325 - 325

Published: March 27, 2024

Atherosclerosis (AS) is a severe vascular disease that results in millions of cases mortality each year. The development atherosclerosis associated with structural lesions, characterized by the accumulation immune cells, mesenchymal lipids, and an extracellular matrix at intimal resulting formation atheromatous plaque. AS involves complex interactions among various cell types, including macrophages, endothelial cells (ECs), smooth muscle (SMCs). Endothelial dysfunction plays essential role initiation progression AS. can encompass constellation non-adaptive dynamic alterations biology function, termed “endothelial reprogramming”. This phenomenon transitioning from quiescent, anti-inflammatory state to pro-inflammatory proatherogenic identity, such as transition (EndMT) endothelial-to-immune cell-like (EndIT). Targeting these processes restore balance prevent identity shifts, alongside modulating epigenetic factors, attenuate progression. In present review, we discuss summarize studies reprogramming pathogenesis

Language: Английский

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In-Depth Genomic Analysis: The New Challenge in Congenital Heart Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1734 - 1734

Published: Feb. 1, 2024

The use of next-generation sequencing has provided new insights into the causes and mechanisms congenital heart disease (CHD). Examinations whole exome sequence have detected detrimental gene variations modifying single or contiguous nucleotides, which are characterised as pathogenic based on statistical assessments families correlations with disease, elevated expression during development, reductions in harmful protein-coding mutations general population. Patients CHD extracardiac abnormalities enriched for classes meeting these criteria, supporting a common set pathways organogenesis CHDs. Single-cell transcriptomics data revealed genes associated specific cell types, emerging evidence suggests that genetic disrupt multicellular essential cardiogenesis. Metrics units being tracked whole-genome studies.

Language: Английский

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Vascular Extracellular Matrix in Atherosclerosis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12017 - 12017

Published: Nov. 8, 2024

The extracellular matrix (ECM) plays a central role in the structural integrity and functionality of cardiovascular system. Moreover, ECM is involved atherosclerotic plaque formation stability. In fact, remodeling affects stability, cellular migration, inflammatory responses. Collagens, fibronectin, laminin, elastin, proteoglycans are crucial proteins during atherosclerosis development. This dynamic driven by proteolytic enzymes such as metalloproteinases (MMPs), cathepsins, serine proteases. Exploring investigating dynamics an important step to designing innovative therapeutic strategies targeting mechanisms, thus offering significant advantages management diseases. review illustrates structure vascular ECM, presenting new perspective on its potential target treatments.

Language: Английский

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