Fibroblast growth factor receptor (FGFR) is expressed in a variety of cells and is involved in their proliferation/migration/survival. To elucidate FGFR-mediated specific action of vascular endothelial cells (ECs) on myocardial ischemia, we generated endothelium-targeted transgenic mice overexpressing constitutively active FGFR2 using Tie2 promoter (FGFR2-Tg). Infarct size, vessel formation and blood perfusion were significantly improved 28 days after myocardial infarction (MI) in FGFR2-Tg, compared with wild-type mice. Aortic ECs isolated from FGFR-Tg showed a marked increase in migratory capacity and tube formation. These in vitro angiogenic activities were blocked by PI3-kinase inhibitor. Whereas, parameters obtained from echocardiography were already improved at three days after MI. Cardiomyocyte apoptosis at the ischemic border zone was decreased in FGFR2-Tg (32.1%, p < 0.05) and cardiac mRNA expression of FGF2 (basic FGF) was also up-regulated (142%, p < 0.05) at 3 days after MI. 1% oxygen-mediated apoptosis was significantly inhibited in FGFR2-Tg-ECs and this inhibition was abolished by PI3-kinase inhibitor. FGFR2-Tg-ECs exposed to 1% oxygen exhibited enhanced phosphorylation of 416-Tyr-Src, 473-Ser-Akt, and HIF1alpha accumulation. The production of FGF2 was enhanced 2.1-fold in FGFR-Tg-ECs under 1% oxygen via the Src/Akt/HIF1alpha pathway, which induced the peri-vessel migration of vascular smooth muscle cells (VSMCs) and anti-apoptotic effects on VSMCs and cardiomyocytes. FGF receptor signaling in ECs promoted migration, survival and autocrine production of FGF2, leading to reduced infarct size, which is associated with anti-apoptotic action in the early stage and with enhanced angiogenesis in the late stage after MI.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.yjmcc.2009.01.015 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Thermodynamics of Surfactant-Enriched Binary-Fluid Systems.
Langmuir
January 2025
Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
Surface-active agents (surfactants) release potential energy as they migrate from one of two adjacent fluids onto their fluid-fluid interface, a process that profoundly impacts the system's energy and entropy householding. The continuum thermodynamics underlying such a surfactant-enriched binary-fluid system has not yet been explored comprehensively. In this article, we present a mathematical description of such a system, in terms of balance laws, equations of state, and permissible constitutive relations and interface conditions, that satisfies the first and second law of thermodynamics.
View Article and Find Full Text PDFHistone deacetylase inhibition with givinostat: a multi-targeted mode of action with the potential to halt the pathological cascade of Duchenne muscular dystrophy.
Front Cell Dev Biol
January 2025
Department of Human Genetics, Leiden University Medical Center (LUMC), Leiden, Netherlands.
Muscle repair and regeneration are complex processes. In Duchenne muscular dystrophy (DMD), these processes are disrupted by the loss of functional dystrophin, a key part of the transmembrane dystrophin-associated glycoprotein complex that stabilizes myofibers, indirectly leading to progressive muscle wasting, subsequent loss of ambulation, respiratory and cardiac insufficiency, and premature death. As part of the DMD pathology, histone deacetylase (HDAC) activity is constitutively increased, leading to epigenetic changes and inhibition of muscle regeneration factors, chronic inflammation, fibrosis, and adipogenesis.
View Article and Find Full Text PDFLooking beyond the ER, PR, and HER2: what's new in the ARsenal for combating breast cancer?
Reprod Biol Endocrinol
January 2025
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
Breast cancer (BrCa) is a complex and heterogeneous disease with diverse molecular subtypes, leading to varied clinical outcomes and posing significant treatment challenges. The increasing global burden of BrCa, particularly in low- and middle-income countries, underscores the urgent need for more effective therapeutic strategies. The androgen receptor (AR), expressed in a substantial proportion of breast cancer cases, has emerged as a potential biomarker and therapeutic target.
View Article and Find Full Text PDFTransient activation of YAP/TAZ confers resistance to morusin-induced apoptosis.
BMC Mol Cell Biol
January 2025
Department of Biological Sciences, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
Background: The Hippo signaling pathway involves a kinase cascade that controls phosphorylation of the effector proteins YAP and TAZ, leading to regulation of cell growth, tissue homeostasis, and apoptosis. Morusin, a compound extracted from Morus alba, has shown potential in cancer therapy by targeting multiple signaling pathways, including the PI3K/Akt/mTOR, JAK/STAT, MAPK/ERK, and apoptosis pathways. This study explores the effects of morusin on YAP activation and its implications for apoptosis resistance.
View Article and Find Full Text PDFCotargeting of thioredoxin 1 and glutamate-cysteine ligase in both imatinib-sensitive and imatinib-resistant CML cells.
Biochem Pharmacol
January 2025
State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, PR China; School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, PR China. Electronic address:
Chronic myeloid leukemia (CML) is a type of malignancy characterized by harboring the oncogene Bcr-Abl, which encodes the constitutively activated tyrosine kinase BCR-ABL. Although tyrosine kinase inhibitors targeting BCR-ABL have revolutionized CML therapy, native and acquired drug resistance commonly remains a great challenge. Thioredoxin 1 (Trx1) and glutamate-cysteine ligase (GCL), which are two major antioxidants that maintain cellular redox homeostasis, are potential targets for cancer therapy and overcoming drug resistance.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!