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Updated: Jan 9, 2026
Transverse Aortic Constriction in Mice
Published on: April 21, 2010
SNX16 aggravates AngII-induced cardiac hypertrophy in mice via EGFR transactivation
Lin Xie1,2,3, Ke Wen1,4, Guan-Hui Yu1,4
1The National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, China.
Insights
Sorting Nexin 16 (SNX16) upregulation promotes cardiac hypertrophy by enhancing epidermal growth factor receptor (EGFR) recycling. Deleting SNX16 in mice inhibited this process, offering potential therapeutic targets for heart failure.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Cellular Trafficking
Background:
- Cardiac hypertrophy is a major risk factor for heart failure and cardiovascular mortality.
- Upregulated Sorting Nexin 16 (SNX16) expression is observed in hypertrophic hearts.
Purpose of the Study:
- To investigate the role of SNX16 in cardiac hypertrophy.
- To elucidate the mechanism by which SNX16 influences cardiac hypertrophy, particularly its relationship with the epidermal growth factor receptor (EGFR) pathway.
Main Methods:
- Utilized a cardiac-specific SNX16 deletion mouse model.
- Administered Angiotensin II (AngII) to induce hypertrophy.
- Examined EGFR transactivation, recycling, and downstream signaling.
- Investigated SNX16 expression and EGFR phosphorylation in human cardiac hypertrophy patient samples.
Main Results:
- Cardiac-specific deletion of SNX16 significantly inhibited AngII-induced cardiac hypertrophy and cardiomyocyte enlargement in male mice.
- SNX16 overexpression and AngII stimulation promoted cardiomyocyte enlargement and EGFR transactivation, effects blocked by an EGFR inhibitor (AZD9291).
- SNX16 deficiency impaired AngII- or EGF-induced EGFR recycling in cardiomyocytes.
- Elevated SNX16 expression and EGFR/Src phosphorylation were confirmed in human hypertrophic heart tissues.
Conclusions:
- SNX16 plays a critical role in AngII-induced cardiac hypertrophy.
- SNX16 facilitates cardiac hypertrophy by enhancing EGFR transactivation through increased EGFR recycling in endosomal trafficking.
- Targeting the SNX16-EGFR axis presents a potential therapeutic strategy for cardiac hypertrophy and heart failure.
Abstract:
Cardiac hypertrophy is an independent risk factor for heart failure (HF) which often leads to cardiovascular disease-related death worldwide. Here we show that the upregulated expressions of Sorting Nexin 16 (SNX16) are evident in the hypertrophic hearts. Cardiac-specific deletion of SNX16 significantly inhibited AngII-induced cardiac hypertrophy and cardiomyocytic enlargement in male mice. In addition, we observed that both AngII stimulation and SNX16 overexpression markedly enlarged cardiomyocytes and promoted EGFR transactivation, and these effects were almost completely abolished by AZD9291, an inhibitor of the EGFR pathway. SNX16 deficiency significantly inhibited AngII- or EGF-induced recycling of EGFR in endosomal trafficking in cardiomyocytes. Finally, the elevated expression of SNX16 and the phosphorylation of EGFR and Src were further confirmed in heart tissues from patients with cardiac hypertrophy. Therefore, the present study demonstrates that SNX16-mediated transactivation of EGFR plays a key role in AngII-induced cardiac hypertrophy via enhancing the recycling of EGFR.
