sq-23377 and Coronary-Artery-Disease

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.. 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.. 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.

Topics: Apoptosis; Calcium Ionophores; Case-Control Studies; Cells, Cultured; Coronary Artery Disease; Coronary Vessels; Down-Regulation; Endothelial Cells; Human Umbilical Vein Endothelial Cells; Humans; Interleukin-11; Ionomycin; Leukocytes; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Organ Culture Techniques; Recombinant Proteins; Signal Transduction; Tetradecanoylphorbol Acetate; Time Factors; Transforming Growth Factor beta1