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


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.
Sutherland
Allison J
AJ
Department of Surgery, The University of Queensland, Royal Brisbane and Women's Hospital, Herston, Queensland 4029, Australia.
Nataatmadja
Maria I
MI
Walker
Philip J
PJ
Cuttle
Leila
L
Garlick
R Bruce
RB
West
Malcolm J
MJ
D000368:Aged; D016022:Case-Control Studies; D049109:Cell Proliferation; D003324:Coronary Artery Disease / Q000209:etiology / Q000473:pathology*; D019332:Endothelin-1 / Q000032:analysis*; D005260:Female; D005355:Fibrosis / Q000473:pathology; D006801:Humans; D008264:Macrophages / Q000166:cytology; D008297:Male; D008323:Mammary Arteries / Q000737:chemistry / Q000473:pathology*; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D009336:Necrosis; D044022:Receptor, Endothelin A / Q000032:analysis; D044023:Receptor, Endothelin B / Q000032:analysis; D017466:Receptors, Endothelin / Q000032:analysis*
D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin