乳内动脉移植物中的血管重塑及其与原位内皮素-1和受体表达的关联。

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

作者信息

Sutherland Allison J, Nataatmadja Maria I, Walker Philip J, Cuttle Leila, Garlick R Bruce, West Malcolm J

机构信息

Department of Surgery, The University of Queensland, Royal Brisbane and Women's Hospital, Herston, Queensland 4029, Australia.

出版信息

Circulation. 2006 Mar 7;113(9):1180-8. doi: 10.1161/CIRCULATIONAHA.105.582890. Epub 2006 Feb 27.

DOI:10.1161/CIRCULATIONAHA.105.582890

PMID:16505174

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.

摘要

背景

血管收缩肽内皮素 -1（ET -1）与动脉粥样硬化性心血管疾病、血管平滑肌细胞（VSMC）生长刺激及内膜增厚有关。ET -1结合两种受体亚型，即内皮素A和B受体，其中ETA受体介导血管收缩和VSMC生长。本研究旨在定量评估动脉重塑变量，并将其与乳内动脉（IMA）中ET -1、ETA和ETB表达的变化进行比较。

方法与结果

收集了55例冠状动脉疾病（CAD）患者（45例男性，10例女性；平均年龄65岁）的标本以及14例对照IMA标本（来自7例男性和7例女性；平均年龄45岁）。通过组织化学和免疫组织化学染色方法评估IMA横截面，以量化中层坏死、纤维化、VSMC生长、ET -1、ETA、ETB和巨噬细胞浸润的水平。患者中层坏死的面积百分比几乎是对照组的两倍（31.85±14.52%对17.10±9.96%，P = 0.0006）。与对照组相比，总胶原蛋白和I型胶原蛋白显著增加（分别为65.8±18.3%对33.7±13.7%，P = 0.07；14.2±10.0%对4.8±2.8%，P = 0.01）。尽管接受了ACE和/或他汀类药物治疗，但患者IMA中ET -1表达和细胞周期相对于对照组仍显著升高（分别为46.27±18.46对8.56±8.42，P = 0.0001；37.29±12.88对11.06±8.18，P = 0.0001）。患者血管中ETA和ETB染色升高（分别为46.88±11.52%对18.58±7.65%，P = 0.0001；42.98±7.08%对34.73±5.20%，P = 0.0067）。在所有切片中均观察到轻度的巨噬细胞存在。