Critical role of angiopoietins/Tie-2 in hyperglycemic exacerbation of myocardial infarction and impaired angiogenesis

Qin Hui Tuo, Heng Zeng, Amanda Stinnett, Heidi Yu, Judy L. Aschner, Daun Fang Liao, Jian Xiong Chen

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) are the two ligands of the Tie-2 receptor, a receptor tyrosine kinase that is expressed on the endothelium. A balanced angiopoietin/Tie-2 system is critical for the maintenance of vascular integrity. We investigated the potential role of a disrupted angiopoietin/Tie-2 system on hyperglycemic exacerbation of myocardial infarction and impaired angiogenesis. Using streptozotocin (STZ) mice subjected to myocardial ischemia, we examined the effects of shifting the Ang-2-to-Ang-1 ratio on myocardial infarction size, apoptosis, bone marrow (BM) cell-endothelial progenitor cell (EPC) differentiation, and angiogenesis. In control mice, myocardial ischemia increased expression of both Ang-2 and Tie-2. In STZ mice, Ang-2 expression was elevated, whereas Tie-2 expression was reduced, and neither was significantly altered by ischemia. Myocardial infarct size and apoptosis were increased in STZ compared with control mice. Using in vivo administration of an adenovirus containing Ang-1 or Ang-2, we found that shifting the Ang-2-to-Ang-1 ratio to favor Ang-1 reduced myocardial apoptosis and infarct size in STZ mice, while shifting the Ang-2-to-Ang-1 ratio to favor Ang-2 resulted in a significant increase in myocardial infarct size and apoptosis in control mice. Myocardial ischemia-stimulated BM cell-EPC differentiation was inhibited and myocardial angiogenesis was reduced in STZ mice. Systemic administration of Ad-Ang-1 restored BM cell-EPC differentiation and increased myocardial VEGF expression and angiogenesis in STZ mice. Our data demonstrate that disturbed angiopoietin/Tie-2 signaling contributes to the hyperglycemic exacerbation of myocardial infarction and impaired angiogenesis. Restoration of the Ang-2-to-Ang-1 ratio may be a novel therapeutic strategy for the treatment of diabetic myocardial ischemic diseases.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume294
Issue number6
DOIs
StatePublished - Jun 2008
Externally publishedYes

Fingerprint

Angiopoietin-2
Angiopoietin-1
Myocardial Infarction
Streptozocin
Bone Marrow Cells
Apoptosis
Myocardial Ischemia
Cell Differentiation
Receptor Protein-Tyrosine Kinases
Cardiomyopathies
Adenoviridae
Vascular Endothelial Growth Factor A
Endothelium
Blood Vessels

Keywords

  • Angiopoietin-1
  • Angiopoietin-2
  • Apoptosis
  • Hyperglycemia

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Critical role of angiopoietins/Tie-2 in hyperglycemic exacerbation of myocardial infarction and impaired angiogenesis. / Tuo, Qin Hui; Zeng, Heng; Stinnett, Amanda; Yu, Heidi; Aschner, Judy L.; Liao, Daun Fang; Chen, Jian Xiong.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 294, No. 6, 06.2008.

Research output: Contribution to journalArticle

Tuo, Qin Hui ; Zeng, Heng ; Stinnett, Amanda ; Yu, Heidi ; Aschner, Judy L. ; Liao, Daun Fang ; Chen, Jian Xiong. / Critical role of angiopoietins/Tie-2 in hyperglycemic exacerbation of myocardial infarction and impaired angiogenesis. In: American Journal of Physiology - Heart and Circulatory Physiology. 2008 ; Vol. 294, No. 6.
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