EFFECTS OF ADIPOSE TISSUE ON ATHEROGENESIS VIA IMMUNOREGULATION AND IMMUNOMODULATION

Abstract: 

Background: Atherosclerosis, a chronic inflammatory disease of the arterial wall, is accelerated by obesity, adipose tissue inflammation and elevated circulating cytokine levels. The modulatory effects of adipokines on the pathogenetic role of specific immune cell subsets in atherosclerosis remain largely unknown.

Aims: To examine how obesity modifies the number, functional differentiation and activation of immune cells in atherosclerotic lesions, and to identify potential targets for therapeutic immunomodulation.

Methods - Workpackages:

  1. WP1 will determine how obesity alters the populations of immune cells in the vessel wall of atherosclerosis-prone mice, the kinetics of cell accumulation, and the molecules and receptors involved in recruitment and activation. Findings will be verified in vascular specimens from patients with cardiovascular disease and correlated with inflammation biomarkers.
  2. WP2 will examine the role of CD11c+ monocytes/dendritic cells and Foxp3+ regulatory T lymphocytes in obesity-associated vascular lesion formation using (conditional) knockout mouse strains.
  3. WP3 will employ molecular imaging to non-invasively visualise and longitudinally follow atherosclerotic lesion composition. The kinetics of CX3CR+ monocyte and Foxp3+ regulatory T cell recruitment will be monitored using reporter-gene transgenic mice or autologous transplantation of fluorescence-labelled cells.
  4. WP4 will examine how adipokines modify macrophage activation via TLR4, focussing on the adaptor protein MyD88, the negative regulator IRAK-M, and anti-inflammatory microRNAs.
  5. Finally, WP5 will test novel therapeutic approaches (CTL4-Ig, monoclonal anti-CD3 or anti-IL2 antibodies) for controlling vascular inflammation in obesity.

Expected results: To obtain a fundamental understanding of the molecular and cellular mechanisms underlying the systemic/endocrine (from abdominal fat) and paracrine (from perivascular adipose tissue) effects of obesity on atherosclerotic lesion growth.

 

FAT VESSEL / MIS 379527

Project info

Acronym:
FAT VESSEL
Coordinating Institution:
Democritus University of Thrace (DUTH)
Scientific Coordinator:
Konstantinides Stavros
Research Team 2 Leader:
Andreakos Evangelos
Research Team 3 Leader:
Tsatsanis Christos

Stats

I.D.:
1174
Mis:
379527
Budget:
594 828.00

Document Library

News

(06-07-2012) Ένταξη της Πράξης «ΘΑΛΗΣ – Δ.Π.Θ. –  ΕΠΙΔΡΑΣΗ ΤΟΥ ΛΙΠΩΔΟΥΣ ΙΣΤΟΥ ΣΤΗΝ ΑΘΗΡΟΓΕΝΕΣΗ ΜΕΣΩ ΑΝΟΣΟΡΥΘΜΙΣΗΣ ΚΑΙ ΑΝΟΣΟΤΡΟΠΟΠΟΙΗΣΗΣ», με MIS: 379527 στο Επιχειρησιακό Πρόγραμμα «ΕΚΠΑΙΔΕΥΣΗ ΚΑΙ ΔΙΑ ΒΙΟΥ ΜΑΘΗΣΗ» 2007-2013.  - ΑΠ10 (PDF|2,6 MB)