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Table 1 Factors common to arteriosclerosis and sclerosing cholangitis

From: Primary sclerosing cholangitis – The arteriosclerosis of the bile duct?

Arteriosclerosis Sclerosing Cholangitis
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
  1. 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.