title: Carvedilol promotes mitochondrial biogenesis by regulating the PGC-1/TFAM pathway in human umbilical vein endothelial cells (HUVECs).
abstract: Carvedilol, a third-generation and nonselective β-adrenoceptor antagonist, is a licensed drug for treating patients suffering from heart failure in clinics. It has been shown that Carvedilol protects cells against mitochondrial dysfunction. However, it's unknown whether Carvedilol affects mitochondrial biogenesis. In this study, we found that treatment with Carvedilol in HUVECs resulted in a significant increase of PGC-1α, NRF1, and TFAM. Notably, Carvedilol significantly increased mtDNA contents and the two mitochondrial proteins, cytochrome C and COX IV. In addition, MitoTracker Red staining results indicated that treatment with Carvedilol increased mitochondria mass. Mechanistically, we found that the effect of Carvedilol on the expression of PGC-1α is mediated by the PKA-CREB pathway. Importantly, our results revealed that stimulation of mitochondrial biogenesis by carvedilol resulted in functional gain of the mitochondria by showing increased oxygen consumption and mitochondrial respiratory rate. The increased expression of PGC-1α and mitochondrial biogenesis induced by Carvedilol might suggest a new mechanism of the therapeutic effects of Carvedilol in heart failure.
authors.affiliation: Department of General Surgery, The Third Xiang Ya Hospital of Central South University, Changsha, 410013, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Yao
authors.affiliation: Vascular and Endovascular Surgery, Louisiana State University Health Sciences Center-Shreveport, 71103, USA.
authors.forename: Wayne W
authors.initials: WW
authors.lastname: Zhang
authors.affiliation: Vascular and Endovascular Surgery, Louisiana State University Health Sciences Center-Shreveport, 71103, USA.
authors.forename: Luyu
authors.initials: L
authors.lastname: Yao
authors.affiliation: Vascular and Endovascular Surgery, Louisiana State University Health Sciences Center-Shreveport, 71103, USA.
authors.forename: Shu
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of General Surgery, The Third Xiang Ya Hospital of Central South University, Changsha, 410013, China.
authors.forename: Wanpin
authors.initials: W
authors.lastname: Nie
authors.affiliation: Department of General Surgery, The Third Xiang Ya Hospital of Central South University, Changsha, 410013, China. Electronic address: huangfz226@yeah.net.
authors.forename: Feizhou
authors.initials: F
authors.lastname: Huang
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D002227:Carbazoles / Q000008:administration & dosage*; D000077261:Carvedilol; D049108:Cell Enlargement / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011412:Propanolamines / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011412:Propanolamines; C499631:TFAM protein, human; D014157:Transcription Factors; D000077261:Carvedilol
keywords: Carvedilol; Endothelium; Mitochondria; PGC-1α