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

作者：Lebastchi Amir H; Qin Lingfeng; Khan Salman F; Zhou Jing; Geirsson Arnar; Kim Richard W; Li Wei; Tellides George^*

来源：Atherosclerosis, 2011, 219(2): 417-424.

DOI：10.1016/j.atherosclerosis.2011.07.121

• Arteriosclerosis
• Smooth muscle cells
• Transforming growth factor-beta
• Human

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.

• 出版日期2011-12