Angiostatin is negatively associated with coronary collateral growth in patients with coronary artery disease

Toshiro Matsunaga, William M. Chilian, Keith March

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Angiostatin, an inhibitor of tumor angiogenesis, is produced by the actions of matrix metalloproteinases (MMP) on plasminogen. Recently, we reported that angiostatin levels are increased in a model of inadequate coronary collateral growth and angiogenesis in response to ischemia, despite high levels of vascular endothelial growth factor (VEGF). We hypothesized that angiostatin levels are negatively associated with collateral formation in patients. Coronary angiograms from 37 patients undergoing coronary bypass surgery were evaluated for the absence of angiographically visible collaterals (Rentrop scores of 0) or the presence of Rentrop classification grade 3 (well developed) collaterals. Pericardial fluid was obtained from each patient during the bypass procedure, and the sample was analyzed for angiostatin, plasminogen, and VEGF (Western analysis) and for combined activities of MMP-2 and MMP-9 (zymographic analysis). In patients with no collaterals, angiostatin level was greater compared with that in patients with well-developed collaterals (3.1 ± 0.2 vs. 2.3 ± 0.1 optical density units, P < 0.05). Neither MMP activities nor VEGF levels were different between the two groups of patients. The higher levels of angiostatin in patients with no visible collaterals were reflective of a higher concentration of plasmin/plasminogen (6.2 ± 0.7 vs. 4.2 ± 0.5 optical density units, P < 0.05) compared with those in patients with well-developed collateral vessels. Our results support the concept that the growth inhibitor angiostatin may have a negative impact on coronary collateral growth in patients. Perhaps therapies attempting to provoke coronary collateral growth should incorporate approaches to limit or neutralize the effects of growth inhibitors.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume288
Issue number5 57-5
DOIs
StatePublished - May 2005

Fingerprint

Angiostatins
Coronary Artery Disease
Growth
Plasminogen
Vascular Endothelial Growth Factor A
Growth Inhibitors
Matrix Metalloproteinases
Angiogenesis Inhibitors
Fibrinolysin
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Angiography
Ischemia

Keywords

  • Matrix metalloproteinase
  • Plasminogen
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Physiology

Cite this

Angiostatin is negatively associated with coronary collateral growth in patients with coronary artery disease. / Matsunaga, Toshiro; Chilian, William M.; March, Keith.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 288, No. 5 57-5, 05.2005.

Research output: Contribution to journalArticle

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