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Updated: Jan 3, 2026

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
PKD deletion promotes autophagy and inhibits hypertrophy in cardiomyocyte
1Postdoctoral Mobile Station of Shandong University of Traditional Chinese Medicine, Shandong, China; Department of Cardiology, Affiliated Hospital of Shandong Academy of Medical Sciences, Shandong, China; Department of Cardiology, Jinan Central Hospital Affiliated to Shandong University, Shandong, China.
Abstract:
Protein kinase D (PKD) plays an important role in the development of cardiac hypertrophy induced by pressure overload. However, the mechanism involved is unclear. This study, using primary cardiomyocyte culture, PKD knockdown and overexpression, and other molecular techniques, tested our hypothesis that PKD pathway mediates cardiac hypertrophy by negatively regulating autophagy in cardiomyocyte. Neonatal cardiomyocytes were isolated from Wistar rats and cell hypertrophy was induced by norepinephrine treatment (PE, 10-4 mol/L), and divided into the following groups: (1) Vehicle; (2) PE; (3) PE + control siRNA; (4) PE + Rapamycin (100 nM); (5) PE + PKD-siRNA (2 × 108 U/0.1 ml); (6) PE + PKD siRNA + 3 MA (10 mM). The results showed that PE treatment induced cardiomyocyte hypertrophy, which were confirmed by cell size and biomarkers of cardiomyocyte hypertrophy including increased ANP and BNP mRNA. PKD knockdown or Rapamycin significantly inhibited PE-induced cardiomyocyte hypertrophy. In addition, PKD siRNA increased autophagy activity determined by electron microscopy, increased biomarkers of autophagy by Western blot, accompanied by down-regulated AKT/mTOR/S6K pathway. All the effects of PKD knockout were inhibited by co-treatment with 3-MA, an autophagy inhibitor. Oppositely, the autophagy in cardiomyocytes was inhibited by PKD overexpression. These results suggest that PKD participates in the development of cardiac hypertrophy by regulating autophagy via AKT/mTOR/S6K pathway.
Insights
Protein kinase D (PKD) promotes cardiac hypertrophy by inhibiting autophagy. Inhibiting PKD or enhancing autophagy prevents this heart condition, revealing a key regulatory pathway.
Area of Science:
- Cardiovascular Biology
- Molecular Cell Biology
- Biochemistry
Background:
- Cardiac hypertrophy is a significant risk factor for heart failure.
- The precise molecular mechanisms underlying cardiac hypertrophy remain incompletely understood.
- Protein kinase D (PKD) is implicated in cardiac hypertrophy development.
Purpose of the Study:
- To investigate the role of Protein kinase D (PKD) in cardiac hypertrophy.
- To elucidate the mechanism by which PKD influences cardiomyocyte size and function.
- To test the hypothesis that PKD negatively regulates autophagy in cardiomyocytes during hypertrophy.
Main Methods:
- Primary neonatal rat cardiomyocyte culture.
- Norepinephrine-induced cardiomyocyte hypertrophy model.
- PKD knockdown (siRNA) and overexpression studies.
- Autophagy modulation using Rapamycin and 3-MA.
- Analysis of cardiomyocyte size, hypertrophy biomarkers (ANP, BNP), and autophagy markers.
- Western blot and electron microscopy.
Main Results:
- Norepinephrine induced cardiomyocyte hypertrophy, increasing ANP and BNP mRNA levels.
- PKD knockdown and Rapamycin significantly attenuated norepinephrine-induced hypertrophy.
- PKD knockdown enhanced autophagy and downregulated the AKT/mTOR/S6K pathway.
- Autophagy inhibition (3-MA) reversed the protective effects of PKD knockdown.
- PKD overexpression suppressed autophagy.
Conclusions:
- PKD plays a crucial role in mediating cardiac hypertrophy.
- PKD regulates cardiac hypertrophy by negatively controlling autophagy.
- The PKD-mediated regulation of autophagy occurs via the AKT/mTOR/S6K signaling pathway.
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