| 1. |
- Chyu, Kuang-Yuh, et al.
(författare)
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Active and passive immunization for atherosclerosis
- 2007
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Ingår i: Current Opinion in Molecular Therapeutics. - 2040-3445. ; 9:2, s. 176-182
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Forskningsöversikt (refereegranskat)abstract
- This review summarizes experimental findings that highlight the role of immune mechanisms in atherosclerosis and the potential atheroprotective effects of active or passive immunization strategies. Immunomodulation therapy appears to be feasible and effective, suggesting that a vaccine for atherosclerosis can be developed for clinical testing. Given the increasing number of patients with atherosclerotic disease on current therapy, a new therapy is needed and an immunization strategy could provide such a possibility. Several questions regarding this approach remain unanswered, however, such as choice of optimal antigens, choice of most effective adjuvants, the optimal route of administration, durability of effects and safety, but cautious optimism remains that a vaccine-based approach has the potential to become a part of the armamentarium for atherosclerotic vascular disease.
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| 2. |
- Chyu, Kuang-Yuh, et al.
(författare)
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Immunization for atherosclerosis
- 2007
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Ingår i: Current Atherosclerosis Reports. - : Springer Science and Business Media LLC. - 1523-3804 .- 1534-6242. ; 9:2, s. 104-109
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Forskningsöversikt (refereegranskat)abstract
- This review summarizes experimental findings that highlight the complex roles of the immune system in atherogenesis. Immune activation can have either proatherogenic or atheroprotective effects. Immune-modulation therapy via an active or passive immunization strategy aims to exploit the atheroprotective aspects of the immune system to modulate atherosclerosis. Several experimental studies have demonstrated that such an approach is feasible and effective, raising the tantalizing possibility that an atheroprotective vaccine can be developed for clinical testing. Several potential immunogens have been identified and tested for their atheroprotective efficacy with variable results. Although several questions such as choice of optimal antigens, choice of most effective adjuvants, the optimal route of administration, durability of effects, and safety remain to be answered, we believe that a vaccine-based approach to manage atherosclerotic cardiovascular disease is a potentially viable paradigm.
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| 3. |
- Dimayuga, Paul C, et al.
(författare)
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T Cell Modulation of Intimal Thickening After Vascular Injury. The Bimodal Role of IFN-{gamma} in Immune Deficiency.
- 2005
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 25:Oct 13, s. 2528-2534
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Tidskriftsartikel (refereegranskat)abstract
- Background - Immune deficiency results in exuberant intimal thickening after arterial injury. The mechanisms involved are not well defined. We investigated the role of T cells and IFN-gamma in the response to injury in normal and immune-deficient Rag-1KO mice. Methods and Results - Carotid arterial injury was induced in wild-type (WT), Rag-1KO mice, and Rag-1KO mice reconstituted with T cell-enriched splenocytes. The exuberant intimal thickening in Rag-1KO mice compared with WT mice 21 days after injury was reduced by T cell transfer (P < 0.01). Exogenous IFN-gamma starting on the day of injury inhibited intimal thickening in Rag-1KO mice. However, antibody neutralization of endogenous IFN-gamma in Rag-1KO mice starting 7 days after injury decreased intimal thickening, indicating that late presence of IFN-gamma promoted intimal thickening in Rag-1KO mice. Results further suggest that the effect of late IFN-gamma in Rag-1KO mice is mediated in part by increased IRF-1 and iNOS expression, coupled with low SOCS1 expression. Conclusion - T cells inhibit intimal thickening in the early stages of the response to injury through basal IFN-gamma secretion. In the Rag-1KO mice, late IFN-gamma expression promotes intimal thickening. These findings add novel insight to conditions of immune deficiency that affect intimal thickening.
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| 4. |
- Nilsson, Jan, et al.
(författare)
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Oxidized lipoprotein autoimmunity: an emerging drug target in cardiovascular disease
- 2006
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Ingår i: Future Lipidology. - : Informa UK Limited. - 1746-0875. ; 1:3, s. 321-330
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Forskningsöversikt (refereegranskat)abstract
- Oxidative modification of low-density lipoprotein (LDL) in the arterial wall is believed to be one of the most important mechanisms involved in the development of atherosclerosis. It is well established that oxidized (Ox)-LDL uptake is responsible for the formation of macrophage foam cells, one of the most characteristic hallmarks of the atherosclerotic plaque, and that the proinflammatory and cytotoxic effects of Ox-LDL play an important role in vascular inflammation and lesion development. More recently, it has become apparent that Ox-LDL is also recognized by the immune system, thus resulting in innate and adaptive immune reactions modulating both Ox-LDL clearance and the vascular inflammatory response. The finding that some of these immune responses have a protective effect against plaque development has focused attention on the potential to develop novel therapies for the prevention and treatment of cardiovascular disease based on the selective activation of this protective immunity by vaccines, or mimicking them directly by using Ox-LDL-specific antibodies.
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| 5. |
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| 6. |
- Nordin Fredrikson, Gunilla, et al.
(författare)
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Identification of Immune Responses Against Aldehyde-Modified Peptide Sequences in ApoB Associated With Cardiovascular Disease.
- 2003
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : The Assoc.. - 1524-4636 .- 1079-5642. ; 23:5, s. 872-878
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Tidskriftsartikel (refereegranskat)abstract
- Objective— Atherosclerosis is associated with an immune response against oxidized LDL, which modulates the progression of the disease process. Methods and Results— Using a library of polypeptides covering the complete sequence of apoB-100, the only major protein of LDL, we have identified over 100 different human antibodies reacting against aldehyde-modified apoB-100 sequences. IgM antibody titer levels decreased with age and were associated with the intima-media thickness of the carotid artery in subjects younger than 60 years. There were also inverse associations between IgM levels and oxidized LDL in plasma. In prospective clinical studies, antibody levels against several aldehyde-modified apoB-100 sites were associated with cardiovascular disease in this age group. Whether this immune response is adaptive (protective) or maladaptive (causal) in atherosclerosis requires further investigation. Conclusions— We have characterized a large number of epitopes within the apoB-100 component of oxidized LDL that provoke an immune response in humans. These findings will make it possible to study the role of immune responses against specific sites in oxidized LDL and to determine whether these immune responses influence the risk for future cardiac events.
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| 7. |
- Nordin Fredrikson, Gunilla, et al.
(författare)
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Inhibition of Atherosclerosis in ApoE-Null Mice by Immunization with ApoB-100 Peptide Sequences.
- 2003
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : The Assoc.. - 1524-4636 .- 1079-5642. ; 23:5, s. 879-884
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Tidskriftsartikel (refereegranskat)abstract
- Objective - LDL oxidation is believed to play an important role in the development of atherosclerosis, and oxidized LDL particles have been shown to become targets for the immune system. Immunization of animals with oxidized LDL results in reduction of atherosclerosis, suggesting an atheroprotective effect of this immune response. Methods and Results - Using a polypeptide library covering the complete sequence of apoB-100, a large number of native and malondialdehyde-modified peptide sequences in apoB-100 that are recognized by antibodies in human plasma were identified. We report here that immunization with apoB-100 peptide sequences, against which high levels of IgG and IgM antibodies are present in healthy human controls, reduce atherosclerosis in apoE-null mice by about 60%. Immunizations with these peptides were also found to increase the collagen content of subvalvular lesions. Conclusions - These studies have identified peptide sequences in apoB-100 that induce immune responses, which inhibits atherosclerosis. This suggests a way of developing an immunization therapy for coronary heart disease.
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| 8. |
- Shah, Prediman K, et al.
(författare)
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Vaccination for atherosclerosis: a novel therapeutic paradigm
- 2004
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Ingår i: Expert Review of Vaccines. - : Informa UK Limited. - 1744-8395 .- 1476-0584. ; 3:6, s. 711-716
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Tidskriftsartikel (refereegranskat)abstract
- Numerous studies have identified a role for the innate and adaptive immune response in atherosclerosis; both pro- and antiatherogenic roles for the immune responses have been demonstrated. Common autoantigens against which an immune response has been identified in experimental and human models of atherosclerosis include oxidized low-density lipopoteins, beta2 glycoprotein 1 and heat shock protein 60. Activation of atheroprotective adaptive immune responses have been demonstrated for oxidized low-density lipoprotein-related antigens. Conversely, atheroprotection has been demonstrated with the induction of immune tolerance through activation of mucosal immunity to heat shock protein 65/60 and beta2 glycoprotein 1. Recent identification of specific immunoreactive antigenic epitopes in the apolipoprotein B-100 component of low density lipoproetin and early experimental observations have provided proof of concept that active vaccination using specific apolipoprotein B-100-related antigens may emerge as a novel immunomodulating atheroprotective strategy.
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| 9. |
- Shah, Prediman K, et al.
(författare)
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Vaccine for Atherosclerosis.
- 2014
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 64:25, s. 2779-2791
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Forskningsöversikt (refereegranskat)abstract
- Atherosclerosis is an immune-mediated inflammatory disease of the arterial wall, with both the innate and adaptive immune systems responding to many endogenous and exogenous antigens. Both proatherogenic as well as atheroprotective roles have been identified for the immune system in atherosclerosis. Hence, it is conceivable that an immunomodulatory strategy via active immunization against many of these antigens could potentially alter the natural history of atherosclerosis. This review discusses: 1) the complex role of important components of the innate and adaptive immune systems in atherogenesis; 2) the nature of many antigens that have been tested successfully in vaccine formulations to reduce atherosclerosis in pre-clinical experimental models; and 3) the potential opportunities and challenges for clinical application of vaccination for atherosclerosis in the future.
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| 10. |
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