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

Edsfeldt, Andreas (författare): Lund University,Lunds universitet,Kardiovaskulär forskning - translationella studier,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Cardiovascular Research - Translational Studies,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine,Department of Clinical Sciences, Malmö, Lund University, Sweden; Wallenberg Centre for Molecular Medicine, Lund University, Sweden; Department of Cardiology, Skåne University Hospital, Sweden.

Singh, Pratibha (författare): Lund University,Lunds universitet,Kardiovaskulär forskning - translationella studier,Forskargrupper vid Lunds universitet,Cardiovascular Research - Translational Studies,Lund University Research Groups,Department of Clinical Sciences, Malmö, Lund University, Sweden.

Matthes, Frank (författare): Lund University,Lunds universitet,Vaskulär biologi,Forskargrupper vid Lunds universitet,Vascular Biology,Lund University Research Groups,Department of Clinical Sciences, Malmö, Lund University, Sweden.

Tengryd, Christoffer (författare): Lund University,Lunds universitet,Kardiovaskulär forskning - translationella studier,Forskargrupper vid Lunds universitet,Cardiovascular Research - Translational Studies,Lund University Research Groups,Department of Clinical Sciences, Malmö, Lund University, Sweden.

Cavalera, Michele (författare): Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Kardiovaskulär forskning - translationella studier,Forskargrupper vid Lunds universitet,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine,Cardiovascular Research - Translational Studies,Lund University Research Groups,Department of Clinical Sciences, Malmö, Lund University, Sweden.

Bengtsson, Eva (författare): Malmö universitet,Malmö University,Lund University,Lunds universitet,Kardiovaskulär forskning - matrix och inflammation i ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Matrix and Inflammation in Atherosclerosis,Lund University Research Groups,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces,Department of Clinical Sciences, Malmö, Lund University, Sweden.

Dunér, Pontus (författare): Lund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups,Department of Clinical Sciences, Malmö, Lund University, Sweden.

Volkov, Petr (författare): Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups,LUDC Bioinformatics Unit, Department of Clinical Sciences, Malmö, Lund University, Sweden; Data Science and Quantitative Biology, Discovery Sciences, R&D, AstraZeneca, Gothenburg, Sweden.

Karadimou, Glykeria (författare): Karolinska Institutet,Karolinska Institute,Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.

Gisterå, Anton (författare): Karolinska Institutet,Karolinska University Hospital

Orho-Melander, Marju (författare): Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups,Department of Clinical Sciences, Malmö, Lund University, Sweden.; Diabetes and Cardiovascular Disease Genetic Epidemiology Unit, Department of Clinical Sciences, Malmö, Lund University, Sweden.

Nilsson, Jan (författare): Lund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups,Department of Clinical Sciences, Malmö, Lund University, Sweden.

Sun, Jiangming (författare): Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Kardiovaskulär forskning - translationella studier,Diabetes - Molecular Metabolism,Lund University Research Groups,Cardiovascular Research - Translational Studies,Department of Clinical Sciences, Malmö, Lund University, Sweden.

Gonçalves, Isabel (författare): Lund University,Lunds universitet,Kardiovaskulär forskning - translationella studier,Forskargrupper vid Lunds universitet,Cardiovascular Research - Translational Studies,Lund University Research Groups,Department of Clinical Sciences, Malmö, Lund University, Sweden.; Department of Cardiology, Skåne University Hospital, Sweden.

(creator_code:org_t)

Oxford University Press, 2023
2023
Engelska.
Ingår i: Cardiovascular Research. - : Oxford University Press. - 0008-6363 .- 1755-3245. ; 119:11, s. 2061-2073

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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.

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Av författaren/redakt...: Edsfeldt, Andrea ...; Singh, Pratibha; Matthes, Frank; Tengryd, Christo ...; Cavalera, Michel ...; Bengtsson, Eva; visa fler...; Dunér, Pontus; Volkov, Petr; Karadimou, Glyke ...; Gisterå, Anton; Orho-Melander, M ...; Nilsson, Jan; Sun, Jiangming; Gonçalves, Isabe ...; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Kardiologi

Artiklar i publikationen: Cardiovascular R ...

Av lärosätet: Lunds universitet; Malmö universitet; Karolinska Institutet

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