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Role of CCR2 in the Development of Streptozotocin-Treated Diabetic Cardiomyopathy

Xin Tan1,2, Lizhi Hu1, Zhiping Shu3

  • 1Clinical Center for Human Genomic Research, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.

Diabetes
|August 24, 2019
PubMed

Insights

Chemokine receptor 2 (CCR2) exacerbates diabetic cardiomyopathy by promoting cardiac inflammation and oxidative stress. Blocking CCR2 activity offers a potential therapeutic strategy for managing this diabetes complication.

Area of Science:

  • Cardiovascular Research
  • Endocrinology
  • Immunology

Background:

  • Diabetes mellitus is a significant risk factor for cardiovascular complications.
  • Diabetic cardiomyopathy, a distinct cardiac dysfunction in diabetes, lacks targeted therapies.
  • The role of chemokine receptor 2 (CCR2) in diabetic cardiomyopathy remains unexplored.

Purpose of the Study:

  • To investigate the specific role of cardiac CCR2 in the development of diabetic cardiomyopathy.
  • To evaluate CCR2 as a potential therapeutic target for diabetic heart disease.

Main Methods:

  • A mouse model of streptozotocin (STZ)-induced diabetic cardiomyopathy was established.
  • CCR2 knockout mice and CCR2 inhibitor treatments were employed.
  • Cardiac function, fibrosis, apoptosis, reactive oxygen species (ROS) production, and immune cell polarization were assessed.

Main Results:

  • CCR2 expression was upregulated in the hearts of STZ-induced diabetic mice.
  • CCR2 knockout significantly ameliorated cardiac dysfunction, fibrosis, apoptosis, and ROS production.
  • CCR2 deletion promoted M2 macrophage polarization and CCR2 inhibition reversed hyperglycemia-induced cardiac dysfunction.

Conclusions:

  • Cardiac CCR2 plays a critical role in mediating inflammation and oxidative stress in diabetic cardiomyopathy.
  • CCR2 inhibition demonstrates therapeutic potential for treating diabetic cardiomyopathy.
  • CCR2 represents a promising novel therapeutic target for diabetic heart disease.

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