Carvedilol promotes mitochondrial biogenesis by regulating the PGC-1/TFAM pathway in human umbilical vein endothelial cells (HUVECs)

Biochemical and Biophysical Research Communications
Kai YaoFeizhou Huang

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.

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Citations

Sep 25, 2018·Journal of Cellular and Molecular Medicine·Heike WankaJörg Peters
Apr 13, 2020·Journal of Cellular and Molecular Medicine·Lucia-Doina Popov
Feb 26, 2020·Archives of Physiology and Biochemistry·Dan ChenLongguang Li
May 7, 2020·Signal Transduction and Targeted Therapy·Yang LiuJinliang Xing
Apr 2, 2016·International Neurourology Journal·Jubert MarquezJin Han
Feb 13, 2021·Oxidative Medicine and Cellular Longevity·Rodrigo CarrascoPaaladinesh Thavendiranathan

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