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

Abstract

OBJECTIVE:

Despite pro-fibrotic effects, transforming growth factor (TGF)-β prevents arteriosclerosis by suppressing effector leukocytes and promoting smooth muscle differentiation. However, previous observations of increased TGF-β expression in arteriosclerotic plaques are not consistent with that of an effective protective factor. We investigated the expression, regulation, and responses of TGF-β in human arterial tissues and cells.

METHODS AND RESULTS:

The expression of TGF-β by intrinsic vascular cells was lower in arteriosclerotic than non-diseased coronary arteries. Activation of resident and infiltrating leukocytes did not elicit TGF-β production from coronary artery segments in organ culture. Instead, the basal expression of TGF-β 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-β expression. Isolated cell types representing those found in the artery wall were all capable of signaling in response to TGF-β, 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-β by quiescent human vascular cells. Induction of interleukin-11 may contribute to the anti-arteriosclerotic actions of TGF-β.

• Authors: Amir H Lebastchi, Lingfeng Qin, Salman F Khan, Jing Zhou, Arnar Geirsson, Richard W Kim, Wei Li, George Tellides
• Journal: Atherosclerosis (Atherosclerosis) Vol. 219 Issue 2 Pg. 417-24 (Dec 2011) ISSN: 1879-1484 [Electronic] Ireland
• PMID: 21862019 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Published by Elsevier Ireland Ltd.

Chemical References

• Calcium Ionophores
• IL11 protein, human
• Interleukin-11
• Recombinant Proteins
• TGFB1 protein, human
• Transforming Growth Factor beta1
• Ionomycin
• Tetradecanoylphorbol Acetate

Topics

• Apoptosis (drug effects)
• Calcium Ionophores (pharmacology)
• Case-Control Studies
• Cells, Cultured
• Coronary Artery Disease (immunology, metabolism, pathology, prevention & control)
• Coronary Vessels (drug effects, metabolism)
• Down-Regulation
• Endothelial Cells (drug effects, immunology, metabolism, pathology)
• Human Umbilical Vein Endothelial Cells (drug effects, metabolism)
• Humans
• Interleukin-11 (metabolism)
• Ionomycin (pharmacology)
• Leukocytes (drug effects, immunology)
• Muscle, Smooth, Vascular (drug effects, immunology, metabolism, pathology)
• Myocytes, Smooth Muscle (drug effects, immunology, metabolism, pathology)
• Organ Culture Techniques
• Recombinant Proteins (metabolism)
• Signal Transduction (drug effects)
• Tetradecanoylphorbol Acetate (pharmacology)
• Time Factors
• Transforming Growth Factor beta1 (metabolism)