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Dr. Shyue, Song-Kun

Associate Research Fellow
  • 02-27899153 (Lab) (Room No: N337)
  • 02-26523962 (Office)
  • 02-27829224 (Fax)

Specialty:
  • Caveolin-1
  • Protein Degradation
  • PGs & Cardiovascular Diseases
  • Adenovirus vector gene therapy
     

Education and Positions:
  • Ph.D. Univ. of Texas-Houston, Health Science Center


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Atypical antipsychotics and CD36 pathway

Dr. Shyue, Song-Kun
Metabolism: clinical and experimental, Aug 06, 2021

 

 

Background

Clinical reports indicate that schizophrenia patients taking atypical antipsychotic drugs suffer from metabolism diseases including atherosclerosis. However, the mechanisms underlying the detrimental effect of atypical antipsychotic drugs on atherosclerosis remain to be explored.

Methods

In this study, we used apolipoprotein E-deficient (apoe−/−) hyperlipidemic mice and apoe−/−cd36−/− mice to investigate the underlying mechanism of atypical antipsychotic drugs on atherosclerosis and macrophage-foam cells.

Results

In vivo studies showed that genetic deletion of cd36 gene ablated the pro-atherogenic effect of olanzapine in apoe−/− mice. Moreover, in vitro studies revealed that genetic deletion or siRNA-mediated knockdown of cd36 or pharmacological inhibition of CD36 prevented atypical antipsychotic drugs-induced oxLDL accumulation in macrophages. Additionally, olanzapine and clozapine activated NADPH oxidase (NOX) to generate reactive oxygen species (ROS) which upregulated the activity of peroxisome proliferator-activated receptor γ (PPARγ) and subsequently elevated CD36 expression. Inhibition of NOX activity, ROS production or PPARγ activity suppressed CD36 expression and abolished the detrimental effects of olanzapine and clozapine on oxLDL accumulation in macrophages.

Conclusion

Collectively, our results suggest that atypical antipsychotic drugs exacerbate atherosclerosis and macrophage-foam cell formation by activating the NOX-ROS-PPARγ-CD36 pathway.