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 and 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: 1180-1188. doi:10.1161/CIRCULATIONAHA.105.582890

Author Sutherland, Allison J.
Nataatmadja, Maria I.
Walker, Philip J.
Cuttle, Leila
Garlick, R. Bruce
West, Malcolm J.
Title Vascular remodeling in the internal mammary artery graft and association with in situ endothelin-1 and receptor expression
Journal name Circulation   Check publisher's open access policy
ISSN 0009-7322
Publication date 2006
Sub-type Article (original research)
DOI 10.1161/CIRCULATIONAHA.105.582890
Volume 113
Issue 9
Start page 1180
End page 1188
Total pages 9
Editor J. Loscalzo
Place of publication Baltimore, U.S.A.
Publisher Lippincott Williams & Wilkins
Collection year 2006
Language eng
Subject C1
110201 Cardiology (incl. Cardiovascular Diseases)
110316 Pathology (excl. Oral Pathology)
110323 Surgery
Formatted abstract
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.

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.
Keyword Cardiac & Cardiovascular Systems
Peripheral Vascular Disease
Coronary Disease
Coronary-bypass Grafts
Nitric-oxide Synthase
Q-Index Code C1

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Created: Wed, 15 Aug 2007, 08:14:21 EST