Isoforskolin, adenylate cyclase agonist, inhibits endothelial-to-mesenchymal transition in atherosclerosis

Phytomedicine, Journal Year: 2025, Volume and Issue: 139, P. 156520 - 156520

Published: Feb. 16, 2025

Language: Английский

---

Secretomes From Non‐Small Cell Lung Cancer Cells Induce Endothelial Plasticity Through a Partial Endothelial‐to‐Mesenchymal Transition

Cancer Medicine, Journal Year: 2025, Volume and Issue: 14(5)

Published: March 1, 2025

The tumor microenvironment (TME) of non-small cell lung cancer (NSCLC) is highly heterogeneous and involved in tumorigenesis resistance to therapy. Among the cells TME, endothelial are associated with latter processes through endothelial-to-mesenchymal transition (EndMT). During EndMT, (ECs) progressively lose their phenotype favor a mesenchymal phenotype, which favors production cancer-associated fibroblasts (CAFs). Our study aimed investigate consequences exposure different secretomes on EC plasticity. Conditioned media (CM) were prepared from lines A549, H1755, H23, H1437, H1975. Proliferation migration ECs treated these CMs assessed by Cyquant Incucyte technologies, respectively. angiogenic capacity was following tubulogenesis Matrigel. Phenotypic changes detected flow cytometry. Morphological analysis actin fibers performed immunohistochemistry, while proteomic mass spectrometry used identify protein content secretomes. A change found when human umbilical vein (HUVECs) CMs. This phenotypic morphological change, an increase both stress fiber expression spontaneous migration. Furthermore, markers (α-SMA CD44) confirmed changes. However, did not modify rate double-labeled (vWF+/α-SMA+ or CD31+/CD44+). Proteomic identified potential targets EndMT therapeutic relevance. Taken together, data suggest that can induce partial EndMT.

Language: Английский

---

Metaboloepigenetics: Role in the Regulation of Flow-Mediated Endothelial (Dys)Function and Atherosclerosis

Cells, Journal Year: 2025, Volume and Issue: 14(5), P. 378 - 378

Published: March 5, 2025

Endothelial dysfunction is the main initiating factor in atherosclerosis. Through mechanotransduction, shear stress regulates endothelial cell function both homeostatic and diseased states. Accumulating evidence reveals that epigenetic changes play critical roles etiology of cardiovascular diseases, including The metabolic regulation epigenetics has emerged as an important control gene expression states, but to best our knowledge, this connection remains largely unexplored In review, we (1) summarize how (or flow) (dys)function; (2) explore alterations occur endothelium response disturbed flow; (3) review metabolism under different conditions; (4) suggest mechanisms which may link altered epigenome by modulations metabolite availability. We believe plays role reprogramming could pave way for novel metabolism-based therapeutic strategies.

Language: Английский

---

SNAI2, a potential crossing point between cancer and cardiovascular disease

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(5)

Published: March 9, 2025

Cancer and cardiovascular disease remain the leading causes of morbidity mortality worldwide, two separate entities share several similarities possible interactions. Patients with cancer may have underlying disease, which is often exacerbated by stress tumor growth or treatment. At same time, cardiotoxicity induced anti-cancer therapies malignant process itself can lead to new diseases. Efforts been made find a rational explanation for this phenomenon. As classical tumor-promoting factor, we notice that SNAI2 simultaneously plays an important pathogenic role in Moreover, there are striking parallels mechanisms CVD, such as shared risk factors (e.g., smoking diabetes), cellular phenotypic switching, metabolic remodeling, all mediated SNAI2. This review aims summarize SNAI2's core linking well explore therapeutic approaches targeting also seeks provide insights into common both CVD.

Language: Английский

---

PD-1 inhibition disrupts collagen homeostasis and aggravates cardiac dysfunction through endothelial-fibroblast crosstalk and EndMT

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 17, 2025

Cardiac immune-related adverse events (irAEs) from PD-1-targeting immune check-point inhibitors (ICIs) are an increasing concern due to their high mortality rate. Collagen plays a crucial role in maintaining cardiac structure, elasticity, and signal transduction; however, the effects mechanisms of PD-1 inhibitor on collagen remodeling remain poorly understood. C57BL/6 mice were injected with anti-mouse antibody create inhibitor-treated model. function was measured by echocardiography, distribution analyzed Masson's trichrome staining Sirius Red staining. Single-nucleus RNA sequencing performed examine inhibition gene expression fibroblasts (CFs) endothelial cells (ECs). EC-CF crosstalk assessed using co-culture experiments ELISA. ChIP assay analyze regulation TCF12 TGF-β1 promoter. Western blot, qRT-PCR, immunofluorescence used detect TCF12, TGF-β1, endothelial-to-mesenchymal transition (EndMT) markers. Reactive oxygen species (ROS) levels evaluated DHE staining, MDA content, SOD activity assays. We report newly discovered cardiotoxic effect inhibitor, which causes aberrant heart, marked decrease interstitial increase perivascular deposition. Mechanistically, does not directly affect CFs but instead impact them through crosstalk. reduces secretion ECs downregulating we identify as transcriptional promoter TGF-β1. This subsequently decreases CF activity, leading reduced Additionally, induces EndMT, The dysfunction induced results ROS accumulation ECs. Inhibiting N-acetylcysteine (NAC) preserves normal reversing downregulation EndMT Our suggest that ECs, imbalanced (decrease collagen) heart modulating TCF12/TGF-β1-mediated EndMT. NAC supplementation could be effective clinical strategy mitigate inhibitor-induced dysfunction.

Language: Английский

---

Activity-based trapping for multiplex imaging illuminates the hidden role of endogenous formaldehyde in proinflammatory signaling

Published: March 1, 2025

Language: Английский

---

Integrated metabolomics and network pharmacology analysis to reveal the mechanisms of Wenshenyang decoction in the treatment of chronic kidney disease

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 30, 2025

Background Wenshenyang decoction (WSY) has been shown to have a considerable effect on restoring renal function and improving kidney Yang deficiency syndrome in patients with CKD. However, its mechanism remains unclear. Aims This study aimed integrated metabolomics network pharmacology analysis combined vitro experiments reveal the mechanisms. Materials methods Patients were selected from clinical trial. LC-MS (Liquid chromatography-mass spectrometry) was used investigate differential metabolites pathways. Spearman correlation performed between phenotypes. “Drug-component-differential metabolite” constructed predict core components hub genes, validated by molecular docking. On this basis, effects of WSY viability Human Kidney-2 cells (HK-2) induced doxorubicin (DOX) detected CCK-8, RT-qPCR (Reverse transcription quantitative polymerase chain reaction) detect mRNA expression level genes related targets. Key findings 54 metabolites, which 35 showed up regulated, 19 decreased. that correlated phenotype. KEGG (Kyoto Encyclopedia Genes Genomes) enrichment mainly affected linoleic acid metabolism, FcεRI signaling pathway, unsaturated fatty biosynthesis. The quercetin, luteolin kaempferol, PTGS2, AKT1, MMP9, EGFR MMP2. Molecular docking they had good biological binding capacity. In cell further kaempferol could significantly activate reduce levels EGFR, MMP2, ANGPTL4, increase FGFR1, SIRT3 glucocorticoid receptor (GR). Significance multi-component multi-target properties treatment CKD syndrome, may be anti-inflammatory anti-fibrotic effects. provides methodological reference for

Language: Английский

---

Empagliflozin attenuating renal interstitial fibrosis in diabetic kidney disease by inhibiting lymphangiogenesis and lymphatic endothelial-to-mesenchymal transition via the VEGF-C/VEGFR3 pathway

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 180, P. 117589 - 117589

Published: Oct. 16, 2024

Language: Английский

---

Endothelial Cpt1a Inhibits Neonatal Hyperoxia‐Induced Pulmonary Vascular Remodeling by Repressing Endothelial‐Mesenchymal Transition

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 12, 2025

Abstract Pulmonary hypertension (PH) increases the mortality of preterm infants with bronchopulmonary dysplasia (BPD). There are no curative therapies for this disease. Lung endothelial carnitine palmitoyltransferase 1a (Cpt1a), rate‐limiting enzyme shuttle system, is reduced in a rodent model BPD. It unknown whether Cpt1a reduction causes pulmonary vascular (PV) remodeling. The latter can be result endothelial‐mesenchymal transition (EndoMT). Here, cell (EC)‐specific KO and WT mice (<12 h old) exposed to hyperoxia (70% O 2 ) 14 days allow them recover normoxia until postnatal day 28. Hyperoxia PH, which aggravated EC‐specific mice. Upregulating expression inhibits hyperoxia‐induced PV lung EndoMT, detected by immunofluorescence, scRNA‐sequencing, EC lineage tracing, further increased Blocking EndoMT Male under same high oxygen conditions develop higher degree PH than females, associated expression. Conclusively, neonatal decreasing upregulating EndoMT. This provides valuable strategy developing targeted levels or inhibiting treat BPD‐associated PH.

Language: Английский

---

Intranuclear TCA and mitochondrial overload: the nascent sprout of tumors metabolism

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217527 - 217527

Published: Feb. 1, 2025

Language: Английский

---