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(Circulation. 2006;113:1180-1188.)
© 2006 American Heart Association, Inc.

Cardiovascular Surgery

Vascular Remodeling in the Internal Mammary Artery Graft and Association With In Situ Endothelin-1 and Receptor Expression

Allison J. Sutherland, BSc (Hons), PhD; Maria I. Nataatmadja, MDSc, PhD; Philip J. Walker, MBBS, FRACS; Leila Cuttle, BSc (Hons); R. Bruce Garlick, MBBS (Hons), FRACS; Malcolm J. West, MBBS, PhD, FRACP

From the Department of Surgery, The University of Queensland, Royal Brisbane and Women’s Hospital (A.J.S., P.J.W.); Department of Medicine, The University of Queensland, The Prince Charles Hospital (M.I.N., M.J.W.); Department of Paediatrics and Child Health, The University of Queensland, Royal Children’s Hospital Research Centre (L.C.); and Department of Cardiac Surgery, The Prince Charles Hospital and Holy Spirit Northside Hospital (R.B.G.), Brisbane, Australia.

Correspondence to Allison Sutherland, BSc (Hons), PhD, Department of Surgery, The University of Queensland, Clinical Sciences Bldg, Royal Brisbane and Women’s Hospital, Herston Rd, Herston, Queensland 4029, Australia.

Received August 15, 2005; revision received November 24, 2005; accepted December 14, 2005.

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 ET_A receptor mediates vasoconstriction and VSMC growth. This study aims to quantitatively assess arterial remodeling variables and compare them with changes in ET-1, ET_A, and ET_B 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, ET_A, ET_B, 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). ET_A and ET_B 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 ET_A expression in the absence of chronic inflammation suggests altered IMA VSMC regulation is fundamental to the remodeling process.

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