Activation of human vascular cells decreases their expression of transforming growth factor-beta

被引：25

作者：

Lebastchi, Amir H. ^{[1
]}

Qin, Lingfeng ^{[1
]}

Khan, Salman F. ^{[1
]}

Zhou, Jing ^{[1
]}

Geirsson, Arnar ^{[1
,2
]}

Kim, Richard W. ^{[1
]}

Li, Wei ^{[1
]}

Tellides, George ^{[1
,2
]}

机构：

[1] Yale Univ, Sch Med, Dept Surg, Interdept Program Vasc Biol & Therapeut, New Haven, CT 06510 USA

[2] Vet Affairs Connecticut Healthcare Syst, West Haven, CT USA

来源：

ATHEROSCLEROSIS | 2011年 / 219卷 / 02期

关键词：

Arteriosclerosis; Smooth muscle cells; Transforming growth factor-beta; Human; SMOOTH-MUSCLE-CELLS; REGULATORY T-CELLS; TGF-BETA; ATHEROSCLEROTIC LESIONS; GENE-EXPRESSION; ACCELERATES ATHEROSCLEROSIS; INTERFERON-GAMMA; MESSENGER-RNA; PROLIFERATION; INJURY;

D O I：

10.1016/j.atherosclerosis.2011.07.121

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Objective: Despite pro-fibrotic effects, transforming growth factor (TGF)-beta prevents arteriosclerosis by suppressing effector leukocytes and promoting smooth muscle differentiation. However, previous observations of increased TGF-beta expression in arteriosclerotic plaques are not consistent with that of an effective protective factor. We investigated the expression, regulation, and responses of TGF-beta in human arterial tissues and cells. Methods and results: The expression of TGF-beta by intrinsic vascular cells was lower in arteriosclerotic than non-diseased coronary arteries. Activation of resident and infiltrating leukocytes did not elicit TGF-beta production from coronary artery segments in organ culture. Instead, the basal expression of TGF-beta by coronary arteries decreased after vessel procurement and ex vivo culture. Activation of cultured smooth muscle cells and endothelial cells with phorbol ester and ionophore also decreased TGF-beta expression. Isolated cell types representing those found in the artery wall were all capable of signaling in response to TGF-beta, however production of the cytoprotective molecule, interleukin-11 was cell type-dependent and restricted to smooth muscle cells and fibroblasts. Interleukin-11 reduced smooth muscle cell apoptosis to T cell effectors. Conclusions: Inflammation and cellular activation diminish the basal expression of TGF-beta by quiescent human vascular cells. Induction of interleukin-11 may contribute to the anti-arteriosclerotic actions of TGF-beta. Published by Elsevier Ireland Ltd.

引用

页码：417 / 424

页数：8

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