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Author Notes:

Corresponding Author: Xiang Song Email: song761231@sina.com

XQ, GC, and XS designed research.

XQ and ML performed research.

XQ, ML, MW, GC, and XS analyzed data and XQ, MW, GC, and XS wrote the paper.

We thank Dr. William C. Claycomb for providing HL-1 cardiomyocytes and Dr. Sandra Garraway for critical reading of this manuscript.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


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).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Pharmacology & Pharmacy
  • adrenergic receptor
  • protein kinase C
  • cardiac fibrosis
  • collagen

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


Journal Title:

Frontiers in Pharmacology


Volume 7, Number DEC


, Pages 495-495

Type of Work:

Article | Final Publisher PDF


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.

Copyright information:

© 2016 Qian, Li, Wagner, Chen and Song.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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