From: Primary sclerosing cholangitis – The arteriosclerosis of the bile duct?
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 |
Abnormal luminal content (blood composition) -Lipoproteins -Oxidized LDL -Oxidized phospholipids -Cholesterol | Abnormal bile composition -Bile acids -Cholesterol (supersaturated bile, oxidized?) -Phospholipids(reduced, oxidized?, metabolites?) |
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) |
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 |
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 |