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Vaccines modulating lipoprotein autoimmunity as a possible future therapy for cardiovascular disease
J Nilsson1, G N Fredrikson, H Björkbacka
1Department of Clinical Sciences, Malmö University Hospital, Lund University, Malmö, Sweden. jan.nilsson@med.lu.se
Abstract:
Current strategies for prevention of cardiovascular disease focus on risk factor intervention. Although these have been proven both safe and effective results from randomized clinical trials suggest that it is difficult to achieve relative risk reductions exceeding 40% with this approach. To further improve efficacy future therapies must aim at targeting the actual disease process in the arterial wall. Emerging evidence have identified an important role of the immune system in atherosclerosis and suggest that modulation of autoimmune responses against oxidized LDL and other antigens in the atherosclerotic plaque represent one possible new approach to disease prevention. Oxidized LDL is targeted by both antibody-mediated and cellular immune responses and as much as 10% of the T cells in atherosclerotic plaques are oxidized LDL-specific. Immune activation in the atherosclerotic plaque is primarily of the pro-inflammatory Th1-type and inhibition Th1 immunity reduces atherosclerosis in experimental animals. Atherosclerosis vaccines based on antigens derived from LDL have been developed to modulate these processes. Their mechanisms of action remain to be full characterized but may involve expression of protective antibodies that facilitate the removal of oxidized LDL and antigen-specific regulatory T cells that counteract Th1 autoimmunity against oxidized LDL. In this review we will discuss the possibilities and challenges encountering the translation of immune-modulatory therapy for atherosclerosis from the experimental stage into the clinic.
Insights
Targeting the immune system offers a novel approach to cardiovascular disease prevention by modulating autoimmune responses against oxidized LDL. This immune-modulatory therapy holds promise for improving upon current risk factor interventions.
Area of Science:
- Immunology
- Cardiovascular Research
- Atherosclerosis Pathogenesis
Background:
- Current cardiovascular disease prevention strategies primarily focus on risk factor intervention, with limited success in achieving substantial risk reduction.
- Emerging evidence highlights the immune system's significant role in atherosclerosis development.
- Targeting the disease process within the arterial wall is crucial for enhanced therapeutic efficacy.
Purpose of the Study:
- To explore immune-modulatory therapies for atherosclerosis, focusing on autoimmune responses against oxidized low-density lipoprotein (LDL).
- To review the potential of atherosclerosis vaccines in modulating immune responses for disease prevention.
- To discuss the challenges and possibilities of translating these experimental immune-based therapies into clinical practice.
Main Methods:
- Review of current literature on the immune system's role in atherosclerosis.
- Analysis of experimental findings related to immune modulation and atherosclerosis vaccines.
- Discussion of the mechanisms underlying immune-modulatory approaches, including antibody and T cell responses.
Main Results:
- Oxidized LDL triggers both antibody-mediated and cellular immune responses in atherosclerosis.
- Pro-inflammatory Th1 immune activation is predominant in atherosclerotic plaques.
- Inhibition of Th1 immunity has shown promise in reducing atherosclerosis in experimental models.
- Atherosclerosis vaccines targeting LDL antigens may induce protective antibodies and regulatory T cells.
Conclusions:
- Immune-modulatory therapies targeting autoimmune responses against oxidized LDL represent a promising new avenue for cardiovascular disease prevention.
- Further research is needed to fully characterize the mechanisms of action for atherosclerosis vaccines.
- Translating these novel immune-based strategies from experimental settings to clinical application presents both opportunities and challenges.
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