| 1. |
- Crisby, Milita, et al.
(författare)
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Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques - Implications for plaque stabilization
- 2001
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Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 1524-4539 .- 0009-7322. ; 103:7, s. 926-933
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Tidskriftsartikel (refereegranskat)abstract
- Background--The clinical benefits of lipid lowering with statins are attributed to changes in plaque composition leading to lesion stability, but supporting clinical data from human studies are lacking. Therefore, we investigated the effect of 3 months of pravastatin treatment on composition of human carotid plaques removed during carotid endarterectomy. Methods and Results--Consecutive patients with symptomatic carotid artery stenosis received 40 mg/d pravastatin (n=11) or no lipid-lowering therapy (n=13; control subjects) for 3 months before scheduled carotid endarterectomy. Carotid Plaque composition was assessed with special stains and immunocytochemistry with quantitative image analysis. Plaques from the pravastatin group had less lipid by oil red O staining (8.2 +/-8.4% versus 23.9 +/- 21.1% of the plaque area, P<0.05), less oxidized LDL immunoreactivity (13.33.6% versus 22.0 +/-6.5%, P<0.001), fewer macrophages (15.010.2% versus 25.3 +/- 12.5%, P<0.05), fewer T cells (11.29.3% versus 24.3 +/- 13.4%, P<0.05), less matrix metalloproteinase 2 (MMP-2) immunoreactivity (3.63.9% versus 8.4 +/-5.3%, P<0.05), greater tissue inhibitor of metalloproteinase 1 (TIMP-1) immunoreactivity (9.06.2% versus 3.1 +/-3.9%, P<0.05), and a higher collagen content by Sirius red staining (12.43.1% versus 7.5 +/-3.5%, P<0.005), Cell death by TUNEL staining was reduced in the pravastatin group (17.77.8% versus 32.0 +/- 12.6%, P<0.05). Conclusions--Pravastatin decreased lipids, lipid oxidation, inflammation, MMP-2, and cell death and increased TIMP-1 and collagen content in human carotid plaques, confirming its plaque-stabilizing effect in humans.
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| 2. |
- Dimayuga, Paul, et al.
(författare)
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Inhibitory effect on arterial injury-induced neointimal formation by adoptive B-cell transfer in Rag-1 knockout mice.
- 2002
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : Lippincott Williams & Wilkins. - 1524-4636 .- 1079-5642. ; 22:4, s. 644-649
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the effect of B-cell reconstitution in immune-deficient Rag-1 knockout (KO) mice subjected to arterial injury. After 21 days, injury induced a 4- to 5-fold increase in neointimal formation in Rag-1 KO mice fed normal chow compared with wild-type (WT) mice (0.020+/-0.0160 [n=8] versus 0.0049+/-0.0022 [n=8] mm(2), respectively; P<0.05) and in western-type diet-fed Rag-1 KO mice compared with WT mice (0.0312+/-0.0174 [n=7] versus 0.0050+/-0.0028 [n=6] mm(2), respectively; P<0.05). To investigate the role of B cells in response to injury, Rag-1 KO mice were reconstituted with B cells derived from the spleens of WT mice, with donors and recipients on the same diet. Reconstitution of Rag-1 KO mice with B cells from WT mice (both fed normal chow) reduced neointimal formation compared with the effect in unreconstituted Rag-1 KO mice (0.0076+/-0.0039 [n=9] versus 0.020+/-0.0160 [n=8] mm(2), respectively; P<0.05). Reconstitution of Rag-1 KO mice with B cells from WT mice (both fed a western diet) reduced neointimal formation compared the effect in Rag-1 KO mice (0.0087+/-0.0037 [n=8] versus 0.0312+/-0.0174 [n=7] mm(2), respectively; P<0.05). Injured carotid arteries from reconstituted Rag-1 KO mice had detectable IgM and IgG, indicating viable transfer of B cells. The results suggest that B cells modulate the response to arterial injury.
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| 3. |
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| 4. |
- Nilsson, Jan, et al.
(författare)
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Atherosclerosis.
- 2004
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Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 37:4, s. 351-355
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Nilsson, Jan, et al.
(författare)
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Inflammation and cholesterol
- 2002
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Ingår i: European Heart Journal Supplements. - : Oxford University Press. - 1520-765X .- 1554-2815. ; 4:Suppl A, s. 18-25
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Tidskriftsartikel (refereegranskat)abstract
- Atherosclerosis develops as a result of a chronic arterial inflammation and intimal Fibrosis. The disease represents in many respects a vascular repair process activated in response to injury caused by toxic breakdown products of aggregated and oxidized lipoproteins. The initial response of the artery involves expression of adhesion molecules and recruitment of leukocytes. Degenerated lipoproteins are removed front the extracellular space by macrophages. If lipoproteins continue to I process becomes chronic and accumulate. the inflammatory cytokines stimulate smooth muscle to migrate into the intima. These cells proliferate and form an atherosclerotic plaque. Plaque cell death and inflammation in response to oxidized lipids and other toxic factors May Cause plaques to rupture.
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| 6. |
- Nilsson, Jan, et al.
(författare)
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Vaccin kan skydda mot ateroskleros. Oxiderat LDL spelar huvudrollen i immunsvaret
- 2004
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Ingår i: Läkartidningen. - : Sveriges Läkarförbund. - 0023-7205 .- 1652-7518. ; :19, s. 1700-1705
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Tidskriftsartikel (refereegranskat)abstract
- I takt med att förståelsen av den viktiga roll som inflammation och immunitet spelar vid utveckling av ateroskleros har ökat har immunsystemet blivit allt mer intressant som mål för prevention och behandling av ateroskleros. Ansamling och oxidering av LDL-partiklar i kärlväggen ger upphov till inflammation, fibros och bildning av aterosklerotiska plack. Samtidigt aktiveras autoimmuna reaktioner mot oxiderat LDL, vilket tycks ha skyddande effekt. De strukturer som dessa skyddande immunreaktioner riktas mot har nu börjat identifieras, vilket kan göra det möjligt att utveckla ett aterosklerosvaccin.
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| 7. |
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| 8. |
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| 9. |
- 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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| 10. |
- 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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