Advanced

Atheroprotective immunity and cardiovascular disease: therapeutic opportunities and challenges.

Nilsson, Jan LU ; Lichtman, Andrew and Tegui, Alain (2015) In Journal of Internal Medicine 278(5). p.507-519
Abstract
Emerging knowledge of the role of atheroprotective immune responses in modulating inflammation and tissue repair in atherosclerotic lesions has provided promising opportunities to develop novel therapies directly targeting the disease process in the artery wall. Regulatory T (Treg) cells have a protective role through release of anti-inflammatory cytokines and suppression of auto-reactive effector T cells. Studies in experimental animals have shown that blocking the generation or action of Treg cells is associated with more aggressive development of atherosclerosis. Conversely, cell transfer and other approaches to expand Treg cell populations in vivo result in reduced atherosclerosis. There have been relatively few clinical studies of... (More)
Emerging knowledge of the role of atheroprotective immune responses in modulating inflammation and tissue repair in atherosclerotic lesions has provided promising opportunities to develop novel therapies directly targeting the disease process in the artery wall. Regulatory T (Treg) cells have a protective role through release of anti-inflammatory cytokines and suppression of auto-reactive effector T cells. Studies in experimental animals have shown that blocking the generation or action of Treg cells is associated with more aggressive development of atherosclerosis. Conversely, cell transfer and other approaches to expand Treg cell populations in vivo result in reduced atherosclerosis. There have been relatively few clinical studies of Treg cells and cardiovascular disease but the available evidence also supports a protective function. These observations have raised hope that it may be possible to develop therapies that act by enforcing the suppressive activities of Treg cells in atherosclerotic lesions. One approach to achieve this goal has been through development of vaccines that stimulate immunological tolerance for plaque antigens. Several pilot vaccines based on LDL-derived antigens have demonstrated promising results in preclinical testing. If such therapies can be shown to be effective also in clinical trials, this could have an important impact on cardiovascular prevention and treatment. Here, we review the current knowledge of the mode of action of atheroprotective immunity and of the ways to stimulate such pathways in experimental settings. The challenges in translating this knowledge into the clinical setting are also discussed within the perspective of the experience of introducing immune-based therapies for other chronic non-infectious diseases. This article is protected by copyright. All rights reserved. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Internal Medicine
volume
278
issue
5
pages
507 - 519
publisher
Wiley-Blackwell Publishing Ltd
external identifiers
  • pmid:25659809
  • wos:000363278500007
  • scopus:84944678181
ISSN
1365-2796
DOI
10.1111/joim.12353
language
English
LU publication?
yes
id
24240e3c-f3ef-4c41-9099-af4ab7861bd3 (old id 5145227)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25659809?dopt=Abstract
date added to LUP
2015-03-04 19:12:42
date last changed
2017-11-05 03:17:38
@article{24240e3c-f3ef-4c41-9099-af4ab7861bd3,
  abstract     = {Emerging knowledge of the role of atheroprotective immune responses in modulating inflammation and tissue repair in atherosclerotic lesions has provided promising opportunities to develop novel therapies directly targeting the disease process in the artery wall. Regulatory T (Treg) cells have a protective role through release of anti-inflammatory cytokines and suppression of auto-reactive effector T cells. Studies in experimental animals have shown that blocking the generation or action of Treg cells is associated with more aggressive development of atherosclerosis. Conversely, cell transfer and other approaches to expand Treg cell populations in vivo result in reduced atherosclerosis. There have been relatively few clinical studies of Treg cells and cardiovascular disease but the available evidence also supports a protective function. These observations have raised hope that it may be possible to develop therapies that act by enforcing the suppressive activities of Treg cells in atherosclerotic lesions. One approach to achieve this goal has been through development of vaccines that stimulate immunological tolerance for plaque antigens. Several pilot vaccines based on LDL-derived antigens have demonstrated promising results in preclinical testing. If such therapies can be shown to be effective also in clinical trials, this could have an important impact on cardiovascular prevention and treatment. Here, we review the current knowledge of the mode of action of atheroprotective immunity and of the ways to stimulate such pathways in experimental settings. The challenges in translating this knowledge into the clinical setting are also discussed within the perspective of the experience of introducing immune-based therapies for other chronic non-infectious diseases. This article is protected by copyright. All rights reserved.},
  author       = {Nilsson, Jan and Lichtman, Andrew and Tegui, Alain},
  issn         = {1365-2796},
  language     = {eng},
  number       = {5},
  pages        = {507--519},
  publisher    = {Wiley-Blackwell Publishing Ltd},
  series       = {Journal of Internal Medicine},
  title        = {Atheroprotective immunity and cardiovascular disease: therapeutic opportunities and challenges.},
  url          = {http://dx.doi.org/10.1111/joim.12353},
  volume       = {278},
  year         = {2015},
}