Doxazosin Stimulates Galectin-3 Expression and Collagen Synthesis in HL-1 Cardiomyocytes Independent of Protein Kinase C PathwayReportar como inadecuado

Doxazosin Stimulates Galectin-3 Expression and Collagen Synthesis in HL-1 Cardiomyocytes Independent of Protein Kinase C Pathway - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Journal Title:

Frontiers in Pharmacology


Volume 7, Number DEC


Frontiers Media S.A. | 2016-12-20, Pages 495-495

Type of Work:

Article | Final Publisher PDF

Abstract: Doxazosin, a drug commonly prescribed for hypertension and prostate disease, increases heart failure risk. However, the underlying mechanism remains unclear. Galectin-3 is an important mediator that plays a pathogenic role in cardiac hypertrophy and heart failure. In the present study, we investigated whether doxazosin could stimulate galectin-3 expression and collagen synthesis in cultured HL-1 cardiomyocytes. We found that doxazosin dose-dependently induced galectin-3 protein expression, with a statistically significant increase in expression with a dose as low as 0.01 μM. Doxazosin upregulated collagen I and a-smooth muscle actin a-SMA protein levels and also induced apoptotic protein caspase-3 in HL-1 cardiomyocytes. Although we previously reported that activation of protein kinase C PKC stimulates galectin-3 expression, blocking the PKC pathway with the PKC inhibitor chelerythrine did not prevent doxazosin-induced galectin-3 and collagen expression. Consistently, doxazosin treatment did not alter total and phosphorylated PKC. These results suggest that doxazosin-stimulated galectin-3 is independent of PKC pathway. To determine if the a1-adrenergic pathway is involved, we pretreated the cells with the irreversible a-adrenergic receptor blocker phenoxybenzamine and found that doxazosin-stimulated galectin-3 and collagen expression was similar to controls, suggesting that doxazosin acts independently of a1-adrenergic receptor blockade. Collectively, we show a novel effect of doxazosin on cardiomycytes by stimulating heart fibrosis factor galectin-3 expression. The mechanism of action of doxazosin is not mediated through either activation of the PKC pathway or antagonism of a1-adrenergic receptors.

Subjects: Health Sciences, Medicine and Surgery - Health Sciences, General - Research Funding: This work was supported by Chinese National Natural Science Foundation Project 81300248, 81570358 to XS, and by NIH grant R01-DK087838 to GC.

Keywords: Science and Technology - Life Sciences and Biomedicine - Pharmacology and Pharmacy - adrenergic receptor - protein kinase C - cardiac fibrosis - collagen - HEART-FAILURE - PRESSURE-OVERLOAD - CARDIAC FIBROSIS - PROSTATE-CANCER - APOPTOSIS - ALPHA - CELLS - HYPERTENSION - DYSFUNCTION - INHIBITION -

Autor: Xiaoqian Qian, Mingyang Li, Mary Wagner, Guangping Chen, Xiang Song,



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