Cellular Signalling, Journal Year: 2023, Volume and Issue: 109, P. 110744 - 110744
Published: June 2, 2023
Language: Английский
Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14
Published: March 28, 2023
Cardiac fibrosis plays an indispensable role in cardiac tissue homeostasis and repair after myocardial infarction (MI). The fibroblast-to-myofibroblast differentiation extracellular matrix collagen deposition are the hallmarks of fibrosis, which modulated by multiple signaling pathways various types cells time-dependent manners. Our understanding development MI has evolved basic clinical researches, regulation fibrotic remodeling may facilitate novel diagnostic therapeutic strategies, finally improve outcomes. Here, we aim to elaborate pathophysiology, examination intervention MI.
Language: Английский
Citations
33
The FASEB Journal, Journal Year: 2024, Volume and Issue: 38(4)
Published: Feb. 15, 2024
Abstract Myocardial infarction (MI) is defined as sudden ischemic death of myocardial tissue. Amphiregulin (Areg) regulates cell survival and crucial for the healing tissues after damage. However, functions mechanisms Areg MI remain unclear. Here, we aimed to investigate Areg's impact on remodeling. Mice model was constructed −/− mice were used. Expression analyzed using western blotting, RT–qPCR, flow cytometry, immunofluorescence staining. Echocardiographic analysis, Masson's trichrome, triphenyltetrazolium chloride staining used assess cardiac function structure. RNA sequencing unbiased analysis. Apoptosis autophagy determined by TUNEL staining, electron microscopy, mRFP‐GFP‐LC3 lentivirus. Lysosomal acidity Lysotracker elevated in infarct border zone MI. It mostly secreted macrophages. deficiency aggravated adverse ventricular remodeling, reflected worsening function, a lower rate, increased scar size, interstitial fibrosis. analyses showed that related epidermal growth factor receptor (EGFR), phosphoinositide 3‐kinase/protein kinase B (PI3K‐Akt), mammalian target rapamycin (mTOR) signaling pathways, V‐ATPase lysosome pathways. Mechanistically, exerts beneficial effects via increasing lysosomal promote autophagosome clearance, activating EGFR/PI3K/Akt/mTOR pathway, subsequently inhibiting excessive formation apoptosis cardiomyocytes. This study provides novel evidence role remodeling regulating identifies potential therapeutic
Language: Английский
Citations
11
Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 246, P. 108421 - 108421
Published: April 19, 2023
Lysophosphatidic acid (LPA) is a simple phospholipid consisting of phosphate group, glycerol moiety, and only one hydrocarbon chain. Despite its chemical structure, LPA plays an important role as essential bioactive signaling molecule via specific six G protein-coupled receptors, LPA1–6. Recent studies, especially those using genetic tools, have revealed diverse physiological pathological roles receptors in almost every organ system. Furthermore, many studies are illuminating detailed mechanisms to orchestrate multiple receptor pathways facilitate their coordinated function. Importantly, these extensive "bench" works now translated into the "bedside" exemplified by approaches targeting LPA1 combat fibrotic diseases. In this review, we discuss implications for clinical application focusing on findings vivo utilizing tools receptors.
Language: Английский
Citations
21
Circulation Research, Journal Year: 2023, Volume and Issue: 133(1), P. 86 - 103
Published: May 30, 2023
Reperfusion therapy is critical to myocardial salvage in the event of a infarction but complicated by ischemia-reperfusion injury (IRI). Limited understanding spatial organization cardiac cells, which governs cellular interaction and function, has hindered search for targeted interventions minimizing deleterious effects IRI.We used imaging mass cytometry characterize distribution dynamics cell phenotypes communities mouse left ventricle following IRI. Heart sections were collected from 12 segments (basal, mid-cavity, apical, apex anterior, lateral, inferior wall) 8 time points (before ischemia [I-0H], postreperfusion [R-0H, R-2H, R-6H, R-12H, R-1D, R-3D, R-7D]), stained with 29 metal-isotope-tagged antibodies. Cell community analysis was performed on reconstructed images, most disease-relevant type target protein selected intervention obtained total 251 multiplexed identified 197 063 single grouped into 23 distinct based structure neighborhoods. The architecture heterogeneous throughout ventricular wall exhibited swift changes Analysis proteins posttranslational modifications cells unveiled 13 modification intensity clusters highlighted increased H3K9me3 (tri-methylated lysine 9 histone H3) as key regulatory response endothelial during middle stage Erasing H3K9 methylation, silencing its methyltransferase Suv39h1 or overexpressing demethylase Kdm4d isolated attenuated dysfunction pathological remodeling vitro, binding significantly at function-related genes upon hypoxia, suppressing tube formation, rescued inhibiting H3K9me3.We mapped spatiotemporal heterogeneity adult heart IRI, uncovered potential therapeutic alleviating
Language: Английский
Citations
18
Pharmacological Research, Journal Year: 2024, Volume and Issue: 205, P. 107245 - 107245
Published: May 29, 2024
Fibrosis is a common pathological process that can affect virtually all the organs, but there are hardly any effective therapeutic options. This has led to an intense search for antifibrotic therapies over last decades, with great number of clinical assays currently underway. We have systematically reviewed current and recently finished trials involved in development new drugs, preclinical studies analyzing relevance each these pharmacological strategies fibrotic processes affecting tissues beyond those being clinically studied. analyze discuss this information aim determining most promising options feasibility extending their value as agents other conditions.
Language: Английский
Citations
7
Future Pharmacology, Journal Year: 2024, Volume and Issue: 4(1), P. 199 - 221
Published: March 4, 2024
Individuals suffering from diverse neuropsychiatric and neurodegenerative disorders often have comparable symptoms, which may underline the implication of shared hereditary influences same biological processes. Lysophosphatidic acid (LPA) is a bioactive phospholipid crucial regulator development adult neuronal systems; hence, it play an important role in onset certain diseases such as Alzheimer’s, Parkinson’s disease, schizophrenia. During development, LPA signaling regulates many cellular processes proliferation, survival, migration, differentiation, cytoskeleton reorganization, DNA synthesis. So far, six lysophosphatidic receptors that respond to been discovered categorized based on their homology. Despite abundance evidence relating activities different pathological conditions, little known about involvement field diseases. The purpose this review define related illnesses stated above order better understand these pathologies provide future novel treatment strategies latest data.
Language: Английский
Citations
4
Open Medicine, Journal Year: 2025, Volume and Issue: 20(1)
Published: Jan. 1, 2025
Abstract Background The specific role of lysophosphatidic acid 2 (LPA ) in deep vein thrombosis (DVT) remains unclear. Methods An inferior vena cava annulus retraction model DVT was established wild-type (WT) and global LPA knockout ( Lpar2 −/− mice. We examined the incidence DVT, wet weight thrombus, length assessed endothelial permeability through Evans blue dye assay vivo, cell viability, (EC) mouse ECs vitro. Proteomics, histopathology, immunohistochemistry, western blotting were employed to investigate DVT. Results deficiency increased vascular promoted progression Histological examination revealed aggravated inflammation thrombus In vitro , resulted ECs. Proteomic results indicated that after may be related tight junction (TJ) protein. agonist, 2-[4-(1,3-dioxo-1 H ,3 -benzoisoquinolin-2-yl)butylsulfamoyl] benzoic acid, significantly reduced as well expression TJ protein zonula occludens-1. Conclusion These data provide a novel mechanism barrier protection
Language: Английский
Citations
0
Journal of Pharmaceutical Analysis, Journal Year: 2024, Volume and Issue: 14(10), P. 100997 - 100997
Published: May 8, 2024
miR-135 is a highly conserved miRNA in mammals and includes miR-135a miR-135b. Recent studies have shown that miR-135b key regulatory factor cardio-cerebrovascular diseases. It involved regulating the pathological process of myocardial infarction, ischemia/reperfusion injury, cardiac hypertrophy, atrial fibrillation, diabetic cardiomyopathy, atherosclerosis, pulmonary hypertension, cerebral Parkinson's disease, Alzheimer's disease. Obviously, an emerging player diseases expected to be important target for treatment However, crucial role its underlying mechanism action has not been reviewed. Therefore, this review, we aimed comprehensively summarize signaling pathway mediated by Drugs targeting related patents, highlighting importance utility as therapeutic diseases, discussed.
Language: Английский
Citations
3
Redox Biology, Journal Year: 2025, Volume and Issue: unknown, P. 103511 - 103511
Published: Jan. 1, 2025
Language: Английский
Citations
0
ACS Omega, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 18, 2025
Ischemeia-reperfusion (I/R) injury is a severe complication after restoring blood perfusion in acute myocardial infarction treatment, which vascular endothelial cell dysfunction considered as the key event to exacerbate injury. We have previously verified protective function of ZNF580 cells, however, impact on I/R and its underlying mechanisms not been explored depth. The purpose present study investigate regulatory role confirm that potential therapeutic candidate for treatment. mechanism was determined via bioinformatics. A model human umbilical vein cells (HUVECs) subsequently established whether protects against this effect exerted through regulation autophagic flow. Our identified 459 differentially expressed genes (DEGs) increased viability gradually restored morphology, cytoplasm full, intracellular structure clear, space significantly reduced HUVECs exposed Both Western blotting reverse transcription-polymerase chain reaction (RT-qPCR) were used detect levels different apoptosis-related proteins, it shown lysosome-associated membrane protein 2 (LAMP2) light 3 (LC3) expressions, markedly decreased 62 (P62) expression. Moreover, lactate dehydrogenase (LDH) supernatant rate apoptosis. promoted autophagosome lysosome fusion flux, thereby protecting from Its possibly related activation adenosine 5'-monophosphate (AMP)-activated kinase (AMPK) signaling pathway.
Language: Английский
Citations
0