Article Figures & Data
Figures
- Fig 1.
RT-PCR data. The bands reveal that endothelin and caveolin are underexpressed in aneurysms, whereas VCAM-1, MMP-2, MMP-9, and TIMP-2 are overexpressed in aneurysms. β-Actin is the control that is equally expressed in both the aneurysm and the control.
Tables
Proteolytic enzymes a1-Antitrypsin,11,15,17 calpain,27 cathepsin B and D,10,27,29 collagenase,11,30 elastase,11 MMP-1,26 MMP-2,11,18 MMP-7,26 MMP-8,26,30 MMP-9,5,11,16,19,20,27-30 MMP-12,30 MMP-14,26 MT1-MMP,11,16 protease inhibitor,15,27 SPARC (also known as osteonectin),10 TIMP-2,11,19 TIMP-310 Apoptosis of smooth muscle cells Actinin,30 heat shock protein,26,27 c-Jun,12 caveolin,26 fas,26 myosin heavy chain,30 titin,27 tumor suppressor 53,26 Inflammatory cell recruitment ACE,11,14,15 albumin,27 angiotensin type 1 receptor,14 β-galactosidase-binding lectin,10 endothelial differentiation factor,26 HLA,10,15 IgG heavy chain,10 Ig-γ light chain,10 NFAT,27 vinculin,10 interferon γ,26,27 interleukins,26,27,29,30 MCP-1,26 neutrophil-activating protein,26 TNF26-28,30 Coagulation cascade Annexin III,26 factor XIII,11 haptoglobin, heme oxygenase,30 plasminogen activator inhibitor-1,11,26,30 PDGF-AA,14,26,27,29 platelet membrane glycoprotein IIIA,28 prothrombin, t-PA,16 thrombin receptor,26,27 thrombomodulin,26 thrombospondin 1,26 transferrin,27 u-PA,11,27 vitronectin15 Extracellular matrix proteins ADAM,27 bFGF,14 bone cartilage proteoglycan,26,29 BMP,26,27 collagen I,10,11,15,21,38 collagen III,10,11,15,21-24 collagen IV,10,11,15,21,25 collagen V,11,21 collagen VIII,11 fibronectin,10,11,38 fibromodulin,30 FK506 binding protein 12,27 insulin-like growth factor,26-28 laminin,11,15,28 lysyl oxidase,11 tenascin,11 TGF-β11,27 Oxidative stress Adenosine A3 receptor,27 alcohol dehydrogenase,26 apolipoprotein E,15,27,29 atrial natriuretic peptide,26 clusterin (apolipoprotein J),26 cytochrome P450,26 endothelin,26 GST,26 HIF-1, lipoxygenase,30 SOD,26 iNOS,11,13,27,30 VEGF,11 VEGF receptor11 Cell signaling pathways Acyl CoA binding protein,29 c-myc,26 calcineurin,27 calmodulin,27 CD86,27 elongation factor 1-δ,10 deoxyribonuclease,27 erythroblastic leukemia viral oncogene homolog 2,27 frizzled,27 glutamate receptor metabotropic,27 heparin-binding epidermal growth factor-like growth factor, insulin responsive glucose transporter 4,26 JNK MAPK,12,26 neuregulin,27 PLC,27 PKC,27,29 Serum- and glucocorticoid-inducible kinases ,27,29 protein phosphatase-1, Ras associated protein 2,27 RAL A GTP-binding protein,29 ras,14 retinoic acid receptor-β,26 rho/rac GEF,27,28 transcription factor egr1,26,27 tryptophan hydroxylase,27 tyrosine receptor kinase26 Note:—MMP indicates matrix metalloproteinase; MT1-MMP, membrane type metalloproteinase-1; SPARC, secreted protein acidic and rich in cysteine; TIMP, tissue inhibitor of metalloproteinase; ACE, angiotensin-converting enzyme; HLA, human leukocyte antigen; NFAT, nuclear factor of activated T cells; MCP, macrophage chemoattractant protein; TNF, tumor necrosis factor; ADAM, a disintegrin and metalloproteinase; PDGF, platelet-derived growth factor; u-PA, urokinase type plasminogen activator; bFGF, basic fibroblast growth factor; BMP, bone morphogenetic protein; TGF, transforming growth factor; SOD, superoxide dismutase; iNOS, inducible nitric-oxide synthase; VEGF, vascular endothelial growth factor; GST, glutathione S-transferase; HIF, hypoxia-inducible factor; JNK, c-Jun NH2-terminal kinase; MAPK, mitogen activated protein kinase; PLC, phospholipase C; PKC, protein kinase C; GEF, guanine nucleotide exchange factor.
Articles demonstrating the relevance of each gene to vascular pathophysiology are cited. The functions of these genes are grouped into 7 pathways that are relevant to intracranial aneurysms.
- Table 2:
The 96 genes that had a statistically significant (P < .05) differential expression between the aneurysm and the control artery
Rank Gene +/− 1 Fast skeletal muscle troponin C mRNA − 2 Haptoglobin mRNA + 3 Endothelial differentiation gene 1 protein + 4 Muscle α-actinin subunit, N′-terminal region − 5 Matrix metalloproteinase 9 + 6 Caveolin − 7 Alcohol dehydrogenase, class I + 8 Endothelin-1 − 9 Myosin light chain 2 10 Osteoglycin − 11 Type VIII collagen α -1 chain − 12 Osteopontin + 13 Neutrophil attractant/activation protein-1 (NAP-1) − 14 Interleukin 1 receptor antagonist + 15 Apolipoprotein E + 16 IL-8 receptor − 17 Cytochrome P4B1 isoform − 18 Monocyte chemoattractant protein-1 (MCP-1) + 19 Tissue inhibitor of metalloproteinase-4 (TIMP-4) + 20 Myosin heavy chain (MHC) − 21 Transforming growth factor-β 2 − 22 Heme oxygenase 1 (HO1) + 23 Al adenosine receptor + 24 Osteonectin + 25 p53 protein − 26 Peroxisome proliferator activated receptor (PPAR) gamma 3 + 27 Cathepsin L + 28 Apolipoprotein B − 29 Elongation factor 1 β + 30 Calmodulin-dependent protein kinase II-delta dash − 31 Secreted frizzled-related protein 2 + 32 Glutathione S-transferase − 33 Vascular cell adhesion molecule (VCAM-1) + 34 Endothelin converting enzyme (ECE1) − 35 Platelet-derived growth factor-β + 36 Matrix metalloproteinase-12 + 37 Decorin=proteoglycan − 38 Galectin-3 + 39 Glycoprotein IIb (GPIIb) + 40 Metallo-elastase, macrophage + 41 Fertilin α subunit − 42 Growth response 1 zinc-finger transcription factor − 43 α2 type I collagen − 44 α3 type IV collagen + 45 Apolipoprotein D + 46 Endothelin B receptor − 47 Insulin-like growth factor 1 precursor (IGF-1) + 48 Neuregulin 1 α isoform − 49 Protein phosphatase-1 catalytic subunit (EC 3.1.3.-) + 50 Heme oxygenase-2 − 51 Class II alcohol dehydrogenase, isozyme 1 + 52 Functional messenger ribonucleoprotein particle major protein p50 − 53 factor XI − 54 Rho-associated-Ser/Thr kinase + 55 Acyl CoA binding protein − 56 Protein kinase Cβ (PKC-β) + 57 Bone morphogenetic protein 2 (BMP-2) − 58 Heat shock protein 47 + 59 Retinoic acid receptor RXR α mRNA + 60 α 1 type X collagen + 61 Coagulation factor VII − 62 Interleukin-2 − 63 Elongation factor 1 delta (Rabef1D) + 64 fas antigen spliced variant − 65 glucose transporter type 4 (GLUT4) − 66 Cellular disintegrin ADAM 6e (ADAM 6e) − 67 Atrial natriuretic polypeptides + 68 Matrix metalloproteinase-2 + 69 Major histocompatibility complex class II RLA-DR-α gene + 70 Tissue inhibitor of metalloproteinase-2 (TIMP2) + 71 Adenosine A3 receptor mRNA − 72 Bone morphogenetic protein 7 − 73 Forkhead transcription factor L2 (FoxL2) gene − 74 Neuronal nitric oxide synthase NOS1 + 75 Tissue-type plasminogen activator mRNA + 76 Endothelin receptor type A − 77 Phosphorylase kinase α subunit mRNA − 78 α-1-antitrypsin + 79 Thrombomodulin precursor (Thbd) − 80 Neutrophil-activating peptide 78 (ENA-78) − 81 Calcineurin A β − 82 α-1 type V collagen (COL5A1) − 83 Interferon γ − 84 NADPH-cytochrome P450 reductase − 85 Fibroblast growth factor − 86 Thrombospondin 2-like protein (THBS2) + 87 Tryptophan hydroxylase − 88 Hyperoxia induced (H1) 1 gene encoding a TIMP + 89 Inducible nitric oxide synthase (NOS2) − 90 Glycoprotein IIIa (GPIIIa) + 91 Elongation factor 1 γ + 92 CD86 − 93 Calmodulin-dependent protein kinase II-γ dash2 − 94 Protein inhibitor of neuronal nitric oxide synthase + 95 Vascular endothelial growth factor receptor 3 + 96 Ksp-cadherin − Note:—The genes are ranked according to the degree of significance of the differential expression. + indicates that the gene was overexpressed in the aneurysm; −, the gene was underexpressed in the aneurysm.
- Table 3:
The differentially expressed genes are grouped into their respective molecular pathways
Proteolytic enzymes Apoptosis of smooth muscle cells α-1-Antitrypsin + Caveolin − Cathepsin L + Fas antigen spliced variant − Cellular disintegrin ADAM 6e − Fast skeletal muscle troponin C mRNA − Hyperoxia induced (HI) 1 gene encoding a TIMP + Galectin-3 + Matrix metalloproteinase-2 + Heat shock protein 47 + Matrix metalloproteinase-9 + Muscle α -actinin subunit, N′-terminal region − Matrix metalloproteinase-12 + Myosin heavy chain (MHC) − Metallo-elastase, macrophage + Myosin light chain 2 − Osteonectin = SPARC + PPAR γ 3 + Tissue inhibitor of metalloproteinase-2 (TIMP-2) + p53 protein − Tissue inhibitor of metalloproteinase-4 (TIMP-4) + Secreted frizzled-related protein 2 + Coagulation cascade Inflammatory cell recruitment Coagulation factor VII − Adhesion molecule VCAM-1 (VCAM-1) + Factor XI − Endothelial differentiation gene 1 protein + Glycoprotein IIb (GPIIb) + Interferon γ − Glycoprotein IIIa (GPIIIa) + Interleukin-1 receptor antagonist + Haptoglobin mRNA + Interleukin-2 − Heme oxygenase-1 (HO1) + Interleukin-8 receptor − Heme oxygenase-2 − MHC class II RLA-DR-α gene + Platelet-derived growth factor-β + Monocyte chemoattractant protein-1 (MCP-1) + Thrombomodulin precursor (inhibitor of coagulation) − Neutrophil-activating peptide 78 (ENA-78) − Thrombospondin 2-like protein (THBS2) + Neutrophil attractant/activation protein-1 (NAP-1) − Tissue-type plasminogen activator mRNA + ECM proteins Oxidative stress α-1 type V collagen (COL5A1) − A1 Adenosine receptor + α-1 type X collagen + A3 Adenosine receptor − α-2 type I collagen − Alcohol dehydrogenase, class I + α-3 type IV collagen +* Apolipoprotein B − Bone morphogenetic protein 2 (BMP-2) − Apolipoprotein E + Bone morphogenetic protein 7 (BMP-7) − Atrial natriuretic polypeptide + Decorin=proteoglycan − Class II alcohol dehydrogenase, isozyme 1 + Fibroblast growth factor − Clone pApoD-L) apolipoprotein D (apoD) + Insulin-like growth factor 1 precursor (IGF-1) + CYP4B1 isoform − Osteoglycin − Endothelin-1 − Osteopontin + Endothelin B receptor − Transforming growth factor-β 2 − Endothelin converting enzyme (ECE1) − Type VIII collagen α -1 chain − Endothelin receptor type A − Glutathione S-transferase − Inducible nitric oxide synthase (NOS2) − NADPH-cytochrome P450 reductase − Neuronal nitric oxide synthase NOS1 + Protein inhibitor of neuronal nitric oxide synthase + Vascular endothelial growth factor receptor 3 + Note:—+ indicates that the gene was overexpressed in the aneurysm; −, the gene was underexpressed in the aneurysm.
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