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Transforming growth factor-β2 is associated with atherosclerotic plaque stability and lower risk for cardiovascular events.


ABSTRACT:

Aims

Transforming growth factor-beta (TGF-β) exists in three isoforms TGF-β1, -β2, and -β3. TGF-β1 has been suggested to be important for maintaining plaque stability, yet the role of TGF-β2 and -β3 in atherosclerosis remains to be investigated.This study explores the association of the three isoforms of TGF-β with plaque stability in the human atherosclerotic disease.

Methods and results

TGF-β1, -β2, and -β3 proteins were quantified in 223 human carotid plaques by immunoassays. Indications for the endarterectomy were: symptomatic carotid plaque with stenosis >70% or without symptoms and >80% stenosis. Plaque mRNA levels were assessed by RNA sequencing. Plaque components and extracellular matrix were measured histologically and biochemically. Matrix metalloproteinases and monocyte chemoattractant protein-1 (MCP-1) was measured with immunoassays. The effect of TGF-β2 on inflammation and protease activity was investigated in vitro using THP-1 and RAW264.7 macrophages. Patients were followed longitudinally for cardiovascular (CV) events.TGF-β2 was the most abundant isoform and was increased at both protein and mRNA levels in asymptomatic plaques. TGF-β2 was the main determinant separating asymptomatic plaques in an Orthogonal Projections to Latent Structures Discriminant Analysis. TGF-β2 correlated positively to features of plaque stability and inversely to markers of plaque vulnerability. TGF-β2 was the only isoform inversely correlated to the matrix-degrading matrix metalloproteinase-9 and inflammation in the plaque tissue. In vitro, TGF-β2 pre-treatment reduced MCP-1 gene and protein levels as well as matrix metalloproteinase-9 gene levels and activity. Patients with plaques with high TGF-β2 levels had a lower risk to suffer from future CV events.

Conclusions

TGF-β2 is the most abundant TGF-β isoform in human plaques and may maintain plaque stability by decreasing inflammation and matrix degradation.

SUBMITTER: Edsfeldt A 

PROVIDER: S-EPMC10478752 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Transforming growth factor-β2 is associated with atherosclerotic plaque stability and lower risk for cardiovascular events.

Edsfeldt Andreas A   Singh Pratibha P   Matthes Frank F   Tengryd Christoffer C   Cavalera Michele M   Bengtsson Eva E   Dunér Pontus P   Volkov Petr P   Karadimou Glykeria G   Gisterå Anton A   Orho-Melander Marju M   Nilsson Jan J   Sun Jiangming J   Gonçalves Isabel I  

Cardiovascular research 20230901 11


<h4>Aims</h4>Transforming growth factor-beta (TGF-β) exists in three isoforms TGF-β1, -β2, and -β3. TGF-β1 has been suggested to be important for maintaining plaque stability, yet the role of TGF-β2 and -β3 in atherosclerosis remains to be investigated.This study explores the association of the three isoforms of TGF-β with plaque stability in the human atherosclerotic disease.<h4>Methods and results</h4>TGF-β1, -β2, and -β3 proteins were quantified in 223 human carotid plaques by immunoassays. I  ...[more]

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