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Factors common to arteriosclerosis and sclerosing cholangitis |
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| Arteriosclerosis |
Sclerosing Cholangitis |
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| Co-factors -Gender: Age below 60, men develop coronary heart disease twice as frequently as women -Infectious agents: e.g. Chlamydia pneumoniae -Systemic inflammation: elevated CRP levels, associated rheumatoid arthritis |
Co-factors -Gender: Males are affected twice as often as females -Infectious agents: e.g. increased prevalence of chlamydial antibodies, pos. immunostaining for LPS in bile duct epithelial cells -Systemic inflammation: elevated CRP levels, strongly associated with inflammatory bowel disease |
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| Abnormal luminal content (blood composition) -Lipoproteins -Oxidized LDL -Oxidized phospholipids -Cholesterol |
Abnormal bile composition -Bile acids -Cholesterol (supersaturated bile, oxidized?) -Phospholipids(reduced, oxidized?, metabolites?) |
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| Activated endothelial cells -Adhesion molecules and receptors: VCAM-1, ICAM-1, PCAM-1, E-selectin, P-selectin, CD39, CD40, CD44, P2Y, CXCRs, ADAMs, NTFs/NTRKs -Cyto- and chemokines: CXCL, MCP-1, TNF-α, IL-1β, IL-6, IL-8, fractalkine, osteopontin -Growth factors: CTGF, PDGF-β, VEGF, EGF, ET-1, TGF-β -Tight junction alterations: ZO-1, claudin-1, induction of NOS (iNOS) |
Activated bile duct epithelial cells -Adhesion molecules and receptors: VCAM-1, ICAM-1, E-selectin, CD39L1, CD40, CD44, P2Y, CXCRs, ADAMs, NTFs/NTRKs -Cyto- and chemokines: CXCL, MCP-1, TNF-α, IL-1β, IL-6, IL-8, fractalkine, osteopontin -Growth factors: CTGF, PDGF-β, VEGF, EGF, ET-1, TGF-β -Tight junction alterations: ZO-1, claudin-1, induction of NOS (iNOS) |
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| Inflammatory cells -Monocytes/macrophage/foam cells: ROS, IL-6, IL-1, TNF-α, MMPs -T cells: INF-γ, TNF-α, IL-1, IL10 |
Inflammatory cells -Neutrophil granulocytes: ROS, IL-6, IL-1, TNF-α, MMPs -T cells: INF-γ, TNF-α, IL-1, IL10 |
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| Smooth muscle cells -MMPs: 1, 2, 3, 8, 9, 13,14 -ADAMTS: 1, 13 -TIMPs: 1, 2, 3 -Growth factors and chemokines: HGF, ET-1, TGF-β, ACE2I, RANTES -Matrix deposition: collagen, elastic fibres, glycoproteins, proteoglycanes |
Periductal myofibroblasts -MMPs: 1, 8, 13 -ADAMTS: 13 -TIMPs: 1, 2, 3, 4 -Growth factors and chemokines: HGF, ET-1, TGF-β, MCP-1, MIP-2, ACE2, RANTES -Matrix deposition: collagen, elastic fibres, glycoproteins, proteoglycanes |
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ACE2, angiotensin converting enzyme II; ADAM, a disintegrin and metalloproteinase domain; ADAMTS, a disintegrin-like metallopeptidase with thrombospondin type 1 motif; CD40-antigen, TNF receptor superfamily; CD44, CD44 antigen; CLDN1; claudin 1; CTGF, connective tissue growth factor; CXCLs chemokines, C-X-C motif ligand; CXCRs, chemokine C-X-C motif receptors; CD39/NTPDase-1, ectonucleoside triphosphate diphosphohydrolase 1;CD39L1/NTPDase-2, ectonucleoside triphosphate diphosphohydrolase 2; EGF, epidermal growth factor;ET-1, endothelin 1; HGF; hepatocyte growth factor; ICAM-1 intercellular adhesion molecule 1; INF-γ, interferon gamma; IL1-β, interleukin 1 beta; IL-6; interleukin 6; IL-8; interleukin 8; Mcp-1; monocyte chemoattractant protein-1; MIP-2, chemokine (C-X-C motif) ligand 2; MMPs, matrix metallopeptidases; NTFs neurotrophins; NTRKs, neurotrophic tyrosine kinase receptor;PCAM-1, polymorph nuclear cell adhesion molecule; PDGF-β; platelet-derived growth factor beta polypeptide); P2Y purinergic receptor G-protein coupled; RANTES, chemokine ligand 5; TGF-β, transforming growth factor beta 1; TIMP1, tissue metallopeptidase inhibitor 1; TJP1, tight junction protein 1; ZO-1, zona occludens 1; TNF-α, tumor necrosis factor-alpha; VCAM-1, vascular cell adhesion molecule 1; VEGF, vascular endothelial growth factor. | |
Fickert et al. Lipids in Health and Disease 2007 6:3 doi:10.1186/1476-511X-6-3 |
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