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

Article

关键词: NITRIC-OXIDE SYNTHASE;    SMOOTH-MUSCLE-CELLS;    CORONARY-ARTERY;    ETA-RECEPTOR;    IMMUNOREACTIVITY;    INHIBITION;    PEPTIDE;    WALL;   

DOI  :  10.1161/CIRCULATIONAHA.105.582890

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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