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2012 ; 347
(1
): 155-75
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Transforming growth factor-? and atherosclerosis: interwoven atherogenic and
atheroprotective aspects
#MMPMID21626289
Toma I
; McCaffrey TA
Cell Tissue Res
2012[Jan]; 347
(1
): 155-75
PMID21626289
show ga
Age-related progression of cardiovascular disease is by far the largest health
problem in the US and involves vascular damage, progressive vascular fibrosis and
the accumulation of lipid-rich atherosclerotic lesions. Advanced lesions can
restrict flow to key organs and can trigger occlusive thrombosis resulting in a
stroke or myocardial infarction. Transforming growth factor-beta (TGF-?) is a
major orchestrator of the fibroproliferative response to tissue damage. In the
early stages of repair, TGF-? is released from platelets and activated from
matrix reservoirs; it then stimulates the chemotaxis of repair cells, modulates
immunity and inflammation and induces matrix production. At later stages, it
negatively regulates fibrosis through its strong antiproliferative and apoptotic
effects on fibrotic cells. In advanced lesions, TGF-? might be important in
arterial calcification, commonly referred to as "hardening of the arteries".
Because TGF-? can signal through multiple pathways, namely the SMADs, a MAPK
pathway and the Rho/ROCK pathways, selective defects in TGF-? signaling can
disrupt otherwise coordinated pathways of tissue regeneration. TGF-? is known to
control cell proliferation, cell migration, matrix synthesis, wound contraction,
calcification and the immune response, all being major components of the
atherosclerotic process. However, many of the effects of TGF-? are essential to
normal tissue repair and thus, TGF-? is often thought to be "atheroprotective".
The present review attempts to parse systematically the known effects of TGF-? on
both the major risk factors for atherosclerosis and to isolate the role of TGF-?
in the many component pathways involved in atherogenesis.