Vascular remodeling in the internal mammary artery graft and association with in situ endothelin-1 and receptor expression

Sutherland, Allison J., Nataatmadja, Maria I., Walker, Philip J., Cuttle, Leila, Garlick, R. Bruce, & West, Malcolm J. (2006) Vascular remodeling in the internal mammary artery graft and association with in situ endothelin-1 and receptor expression. Circulation, 113(9), pp. 1180-1188.

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Abstract

BACKGROUND: The vasoconstricting peptide endothelin-1 (ET-1) has been associated with atherosclerotic cardiovascular disease, vascular smooth muscle cell (VSMC) growth stimulation, and intimal thickening. ET-1 binds 2 receptor subtypes, endothelin A and B, and the ETA receptor mediates vasoconstriction and VSMC growth. This study aims to quantitatively assess arterial remodeling variables and compare them with changes in ET-1, ETA, and ETB expression in the internal mammary artery (IMA).

METHODS AND RESULTS: Specimens from 55 coronary artery disease (CAD) patients (45 men, 10 women; mean age 65 years) and 14 control IMA specimens (from 7 men and 7 women; mean age 45 years) were collected. IMA cross sections were assessed by histochemical and immunohistochemical staining methods to quantify the levels of medionecrosis, fibrosis, VSMC growth, ET-1, ETA, ETB, and macrophage infiltration. The percentage area of medionecrosis in the patients was almost double that in the controls (31.85+/-14.52% versus 17.10+/-9.96%, P=0.0006). Total and type 1 collagen was significantly increased compared with controls (65.8+/-18.3% versus 33.7+/-13.7%, P=0.07, and 14.2+/-10.0% versus 4.8+/-2.8%, P=0.01, respectively). Despite ACE and/or statin therapy, ET-1 expression and cell cycling were significantly elevated in the patient IMAs relative to the controls (46.27+/-18.46 versus 8.56+/-8.42, P=0.0001, and 37.29+/-12.88 versus 11.06+/-8.18, P=0.0001, respectively). ETA and ETB staining was elevated in the patient vessels (46.88+/-11.52% versus 18.58+/-7.65%, P=0.0001, and 42.98+/-7.08% versus 34.73+/-5.20%, P=0.0067, respectively). A mild presence of macrophages was noted in all sections.

CONCLUSIONS: Elevated distribution of collagen indicative of fibrosis coupled with increased cell cycling and high levels of ET-1 and ETA expression in the absence of chronic inflammation suggests altered IMA VSMC regulation is fundamental to the remodeling process.

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ID Code: 67217
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: Aged, Case-Control Studies, Cell Proliferation, Coronary Artery Disease/etiology/*pathology, Endothelin-1/*analysis, Female, Fibrosis/pathology, Humans, Macrophages/cytology, Male, Mammary Arteries/chemistry/*pathology, Middle Aged, Muscle, Smooth, Vascular/pathology, Necrosis, Receptor, Endothelin A/analysis, Receptor, Endothelin B/analysis, Receptors, Endothelin/*analysis
DOI: 10.1161/CIRCULATIONAHA.105.582890
ISSN: 1524-4539
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2006 American Heart Association, Inc.
Deposited On: 26 Feb 2014 23:13
Last Modified: 26 Mar 2014 12:08

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