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CLINICAL RESEARCH: CORONARY ARTERY DISEASE

Reduced pericardial levels of endostatin correlate with collateral development in patients with ischemic heart disease

Vipul R. Panchal, MD^*, Jalees Rehman, MD^*, Anne T. Nguyen, MS^*, John W. Brown, MD, Mark W. Turrentine, MD, Yousuf Mahomed, MD and Keith L. March, MD, PhD^*,*

^* Department of Medicine, Krannert Institute of Cardiology, Indianapolis, Indiana, USA
Department of Surgery, Thoracic Surgery Section, Indiana University School of Medicine, Indianapolis, Indiana, USA

Manuscript received September 15, 2002; revised manuscript received September 14, 2003, accepted October 7, 2003.

^* Reprint requests and correspondence: Dr. Keith L. March, Indiana University School of Medicine, Indiana Center for Vascular Biology and Medicine, Krannert Institute of Cardiology, 975 W. Walnut Street, IB 441, Indianapolis, Indiana 46202, USA.
kmarch{at}iupui.edu

OBJECTIVES: We investigated whether pericardial levels of a pro-angiogenic factor (vascular endothelial growth factor, VEGF) or an anti-angiogenic factor (endostatin) related to the presence of coronary collateral circulation in patients with significant coronary artery disease (CAD).

BACKGROUND: Coronary collateralization favorably alters the prognosis of patients with occlusive CAD. The specific factors that mediate and maintain collateral formation in coronary vessel occlusion are yet to be identified.

METHODS: Coronary angiograms from 39 patients undergoing coronary artery bypass surgery were evaluated for the absence of collaterals (n = 20) or the presence of Rentrop classification grade 3 collaterals (n = 19). Pericardial fluid samples were obtained at the time of surgery and were assayed for the VEGF and endostatin by enzyme-linked immunosorbent assay comparing the two groups of patients.

RESULTS: Vascular endothelial growth factor levels were not significantly different between the groups (28.86 ± 4.67 pg/ml vs. 24.39 ± 3.08 pg/ml, p = 0.43). However, pericardial fluid endostatin levels were nearly 40% lower in patients with grade 3 collateralization compared with those lacking angiographic evidence of collaterals (15.17 ± 1.87 ng/ml vs. 24.25 ± 2.08 ng/ml, p < 0.0025).

CONCLUSIONS: Pericardial fluid levels of endostatin, but not VEGF, are associated with the presence or absence of collaterals in patients with CAD. These data suggest that the angiogenesis inhibitor endostatin levels may locally modulate coronary collateral formation.

Abbreviations and Acronyms   CABG = coronary artery bypass grafting   CAD = coronary artery disease   VEGF = vascular endothelial growth factor

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