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Fong To

Biomedical analyst

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Reduced oxidized LDL in T2D plaques is associated with a greater statin usage but not with future cardiovascular events

Author

  • Pratibha Singh
  • Isabel Goncalves
  • Christoffer Tengryd
  • Mihaela Nitulescu
  • Ana F. Persson
  • Fong To
  • Eva Bengtsson
  • Petr Volkov
  • Marju Orho-Melander
  • Jan Nilsson
  • Andreas Edsfeldt

Summary, in English

BACKGROUND: Type 2 diabetes (T2D) patients are at a greater risk of cardiovascular events due to aggravated atherosclerosis. Oxidized LDL (oxLDL) has been shown to be increased in T2D plaques and suggested to contribute to plaque ruptures. Despite intensified statin treatment during the last decade the higher risk for events remains. Here, we explored if intensified statin treatment was associated with reduced oxLDL in T2D plaques and if oxLDL predicts cardiovascular events, to elucidate whether further plaque oxLDL reduction would be a promising therapeutic target. METHODS: Carotid plaque OxLDL levels and plasma lipoproteins were assessed in 200 patients. Plaque oxLDL was located by immunohistochemistry. Plaque cytokines, cells and scavenger receptor gene expression were quantified by Luminex, immunohistochemistry and RNA sequencing, respectively. Clinical information and events during follow-up were obtained from national registers. RESULTS: Plaque oxLDL levels correlated with markers of inflammatory activity, endothelial activation and plasma LDL cholesterol (r = 0.22-0.32 and p ≤ 0.01 for all). T2D individuals exhibited lower plaque levels of oxLDL, sLOX-1(a marker of endothelial activation) and plasma LDL cholesterol (p = 0.001, p = 0.006 and p = 0.009). No increased gene expression of scavenger receptors was identified in T2D plaques. The lower oxLDL content in T2D plaques was associated with a greater statin usage (p = 0.026). Supporting this, a linear regression model showed that statin treatment was the factor with the strongest association to plaque oxLDL and plasma LDL cholesterol (p < 0.001 for both). However, patients with T2D more frequently suffered from symptoms and yet plaque levels of oxLDL did not predict cardiovascular events in T2D (findings are summarized in Fig. 1a). CONCLUSIONS: This study points out the importance of statin treatment in affecting plaque biology in T2D. It also implies that other biological components, beyond oxLDL, need to be identified and targeted to further reduce the risk of events among T2D patients receiving statin treatment.

Department/s

  • Cardiovascular Research - Translational Studies
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Cardiovascular Research - Matrix and Inflammation in Atherosclerosis
  • Diabetic Complications
  • Diabetes - Cardiovascular Disease
  • EpiHealth: Epidemiology for Health
  • Cardiovascular Research - Immunity and Atherosclerosis
  • WCMM-Wallenberg Centre for Molecular Medicine

Publishing year

2020

Language

English

Publication/Series

Cardiovascular Diabetology

Volume

19

Issue

1

Document type

Journal article

Publisher

BioMed Central (BMC)

Topic

  • Endocrinology and Diabetes
  • Cardiac and Cardiovascular Systems

Keywords

  • Atherosclerosis
  • Carotid stenosis
  • Diabetes mellitus
  • Oxidized low-density lipoproteins

Status

Published

Research group

  • Cardiovascular Research - Translational Studies
  • Cardiovascular Research - Matrix and Inflammation in Atherosclerosis
  • Diabetic Complications
  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Immunity and Atherosclerosis

ISBN/ISSN/Other

  • ISSN: 1475-2840