دورية أكاديمية
AMPK deficiency inhibits fatty acid oxidation in endothelial progenitor cells to aggravate impaired angiogenesis after ischemic stroke in hyperlipidemic mice.
| العنوان: | AMPK deficiency inhibits fatty acid oxidation in endothelial progenitor cells to aggravate impaired angiogenesis after ischemic stroke in hyperlipidemic mice. |
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| المؤلفون: | Zhu J; College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, China., Shi Q; Zhejiang Provincial Key Laboratory of Laboratory Animals and Safety Research, Hangzhou Medical College, Hangzhou, China., Han X; Zhejiang Provincial Key Laboratory of Laboratory Animals and Safety Research, Hangzhou Medical College, Hangzhou, China., Wang M; Department of Pharmacology, College of Pharmacy, Beihua University, Jilin, China., Zhang L; College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, China., Ying H; College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, China.; Zhejiang Provincial Key Laboratory of Laboratory Animals and Safety Research, Hangzhou Medical College, Hangzhou, China., Yu B; College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, China. |
| المصدر: | Brain injury [Brain Inj] 2024 Aug 23; Vol. 38 (10), pp. 835-847. Date of Electronic Publication: 2024 May 08. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Informa Healthcare Country of Publication: England NLM ID: 8710358 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1362-301X (Electronic) Linking ISSN: 02699052 NLM ISO Abbreviation: Brain Inj Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: London : Informa Healthcare Original Publication: London ; New York : Taylor & Francis, c1987- |
| مواضيع طبية MeSH: | Endothelial Progenitor Cells*/metabolism , Hyperlipidemias*/metabolism , Hyperlipidemias*/complications , Fatty Acids*/metabolism , Ischemic Stroke*/metabolism , Mice, Inbred C57BL*, Animals ; Mice ; Male ; Diet, High-Fat/adverse effects ; AMP-Activated Protein Kinases/metabolism ; Disease Models, Animal ; Oxidation-Reduction ; Carnitine O-Palmitoyltransferase/metabolism ; Neovascularization, Physiologic/physiology ; Mice, Knockout ; Angiogenesis |
| مستخلص: | Background: Hyperlipidemia is a risk factor for stroke, and worsens neurological outcome after stroke. Endothelial progenitor cells (EPCs), which become dysfunctional in cerebral ischemia, hold capacity to promote revascularization. Objective: We investigated the role of dyslipidemia in impairment of EPC-mediated angiogenesis in cerebral ischemic mice. Methods and Results: The high fat diet (HFD)-fed mice following by ischemic stroke exhibited increased infarct volumes and neurological severity scores, and poorer angiogenesis. Bone marrow-EPCs treated with palmitic acid (PA) showed impaired functions and inhibited activity of AMP-activated protein kinase (AMPK). Notably, AMPK deficiency aggravated EPC dysfunction, further decreased mitochondrial membrane potential, and increased reactive oxygen species level in EPCs with PA treatment. Furthermore, the expression of fatty acid oxidation (FAO)-related genes was remarkably reduced, and carnitine palmitoyltransferase 1A (CPT1A) protein expression was downregulated in AMPK-deficient EPCs. AMPK deficiency aggravated neurological severity scores and angiogenesis in ischemic brain of HFD-fed mice, accompanied by suppressed protein level of CPT1A. EPC transplantation corrected impaired neurological severity scores and angiogenesis in AMPK-deficient mice. Conclusion: Our findings suggest that AMPK deficiency aggravates poor angiogenesis in ischemic brain by mediating FAO and oxidative stress thereby inducing EPC dysfunction in hyperlipidemic mice. |
| فهرسة مساهمة: | Keywords: AMPK; Hyperlipidemia; angiogenesis; endothelial progenitor cells; fatty acid β-oxidation; ischemic stroke |
| المشرفين على المادة: | 0 (Fatty Acids) EC 2.7.11.31 (AMP-Activated Protein Kinases) EC 2.3.1.21 (Carnitine O-Palmitoyltransferase) |
| تواريخ الأحداث: | Date Created: 20240508 Date Completed: 20240711 Latest Revision: 20240711 |
| رمز التحديث: | 20240711 |
| DOI: | 10.1080/02699052.2024.2349776 |
| PMID: | 38716911 |
| قاعدة البيانات: | MEDLINE |
PDF full text from Publisher | تدمد: | 1362-301X |
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| DOI: | 10.1080/02699052.2024.2349776 |