Genes expressed by endothelial cells and their transcriptional regulation by prolonged unidirectional pulsatile flow
| Protein name . | Gene name . | GenBank* . | Ratio ± SEM† . | Cat‡ . | Protein function . |
|---|---|---|---|---|---|
| β-Actin | ACTB | NM_001101 | 1.1 ± 0.07 | F | Cytoskeletal protein |
| Activin βA | INHBA | NM_002192 | 3.1 ± 1.29 | E | Vascular growth factor |
| ALL1-fused gene from chromosome 1q | AF1Q | NM_006818 | 1.4 ± 0.43 | A | Unknown |
| Amyloid β A4 precursor protein | APP | NM_000484 | 2.3 ± 0.49 | D | Alzheimer disease/hemostasis |
| Annexin II | ANXA2 | NM_004039 | 1.2 ± 0.06 | D | Membrane-binding protein |
| Annexin V | ANXA5 | NM_001154 | 2.2 ± 0.14 | D | Anticoagulant protein |
| ApoL1 | APOL1 | NM_003661 | 2.0 ± 0.19 | C | HDL-associated plasma protein |
| ApoL2 | APOL2 | NM_030882 | 1.7 ± 0.42 | C | Homolog of ApoL1 |
| ApoL3 (CG12_1) | APOL3 | NM_014349 | 3.9 ± 1.40 | C | Homolog of ApoL1 |
| AT7_4_3 | No match | 0.4 ± 0.10 | C | Unknown | |
| Biglycan | BGN | NM_001711 | 1.3 ± 0.41 | D | Extracellular matrix constituent |
| Caveolin 1 | CAV1 | NM_01753 | 0.6 ± 0.13 | D | Main component of caveolae |
| Claudin 5 | CLDN5 | NM_003277 | 2.1 ± 0.43 | A | Tight junction protein |
| Cockayne syndrome, type I | CKN1 | NM_000082 | 5.7 ± 2.35 | C | RNA polymerase II transcription |
| Connexin 40 | GJA5 | NM_005266 | 3.2 ± 0.93 | A | Gap junction protein |
| Cyclin-dependent kinase inhibitor 1A (p21) | CDKN1A | NM_000389 | 1.7 ± 0.62 | A | Cell-cycle regulation |
| Cytochrome P450 1B1 | CYP1B1 | NM_000104 | 26.9 ± 0.08 | A | Hormone metabolism |
| Dermatan sulphate proteoglycan 3 | DSPG3 | NM_004950 | 0.7 ± 0.05 | D | Extracellular matrix constituent |
| Diaphorase | DIA4/NQO1 | NM_000903 | 10.9 ± 5.93 | A | Detoxification/nitric oxide synthesis |
| DKFZp564F053 cDNA clone | AA166719 | 3.7 ± 1.24 | C | Unknown | |
| Early growth response 1 | EGR1 | NM_001964 | 1.2 ± 0.17 | B/D | Transcription factor |
| Endothelial protein C receptor | PROCR | NM_006404 | 1.1 ± 0.24 | D | Anticoagulation |
| eNOS | NOS3 | NM_000603 | 4.0 ± 0.73 | B/D | Nitric oxide synthesis |
| EST 15 | R96525 | 1.7 ± 0.25 | C | Unknown | |
| EST 23 | AI632668 | 1.2 ± 0.30 | C | Unknown | |
| EST 35 | AA455259 | 1.8 ± 0.21 | C | Unknown | |
| EST 41 | AI140281 | 1.7 ± 0.42 | C | Unknown | |
| Ferritin, heavy polypeptide | FTH1 | NM_002032 | 2.5 ± 0.48 | C | Intracellular iron storage |
| Ferritin, light polypeptide | FTL | NM_000146 | 2.0 ± 0.12 | A | Intracellular iron storage |
| Fibronectin 1 | FN1 | X02761 | 3.9 ± 0.59 | D | Extracellular matrix protein |
| G1 to S phase transition 1 | GSPT1 | NM_002094 | 0.5 ± 0.08 | C | Cell-cycle regulation |
| Galectin 8 | LGALS8 | NM_006499 | 4.3 ± 0.73 | C | Carbohydrate binding protein |
| GAPDH | GAPD | NM_002046 | 1.0 ± 0.00 | F | Carbohydrate metabolism |
| Hypothetical protein | NM_014108 | 2.3 ± 1.00 | E | Unknown | |
| Hypothetical protein | FLJ23514 | NM_021827 | 0.6 ± 0.09 | C | Unknown |
| Hypothetical protein | FLJ20003 | N47844 | 1.8 ± 0.30 | C | Unknown |
| Hypothetical protein | T80319 | 2.9 ± 0.58 | A | Unknown | |
| Hypothetical protein | BC004930 | 0.4 ± 0.23 | C | Unknown | |
| Interleukin 8 | IL8 | M28130 | 1.0 ± 0.16 | D/E | Inflammatory cytokine |
| LOX-1 | OLR1 | NM_079167 | 1.0 ± 0.45 | D | Oxidized LDL internalization |
| Lung Krüppel-like factor | KLF2 | NM_016270 | 4.9 ± 1.74 | A | Transcription factor |
| Matrix Gla protein | MGP | NM_000900 | 3.7 ± 1.21 | E | Inhibits extracellular matrix calcification |
| MnSOD | SOD2 | NM_000636 | 1.1 ± 0.61 | B/D | Free radical scavenging |
| Multimerin | MMRN | NM_007351 | 2.0 ± 0.54 | D | Hemostasis |
| PAI-1 | SERPINE1 | NM_000602 | 1.4 ± 0.71 | D | Fibrinolysis/proliferation/migration |
| PECAM-1 | PECAM1 | NM_000442 | 2.1 ± 0.37 | D | (Leukocyte) adhesion receptor |
| Prefoldin 2 | PFDN2 | NM_012394 | 2.2 ± 0.44 | C | Membrane-binding protein/autoantigen |
| Protease nexin 1 | GDN | M17783 | 6.4 ± 3.18 | D | Serine protease inhibitor |
| Rabkinesin 6 | RAB6KIFL | NM_005733 | 3.0 ± 0.55 | C | Intracellular transport/cell division |
| Ras-related C3 botulinum toxin substrate 3 | RAC3 | NM_005052 | 1.6 ± 0.07 | C | Ras-related GTPase |
| Regulator of G protein signaling | RGS5 | R38334 | 1.4 ± 0.77 | C | GTPase activator |
| 28S ribosomal RNA | M11167 | 0.9 ± 0.19 | F | Translation | |
| Ribosomal protein L30 | RPL30 | NM_000989 | 1.1 ± 0.16 | F | Translation |
| Ribosomal protein S11 | RPS11 | NM_001015 | 0.7 ± 0.13 | C | Translation |
| Solute carrier family 7, member 11 | SLC7A11 | NM_014331 | 2.1 ± 0.06 | A | Amino acid transporter |
| Spermidine/spermine N1-acetyltransferase | SAT | NM_002970 | 1.0 ± 0.12 | A | Polyamine metabolism |
| Stromal cell-derived factor 2 | SDF2 | AA343837 | 2.4 ± 0.20 | C | Secretory protein |
| Thioredoxin reductase 1 | TXNRD1 | NM_003330 | 2.0 ± 0.08 | A | Intracellular redox control |
| Thrombin receptor 1 | F2R | NM_001992 | 2.0 ± 0.18 | D | Mitogenic signaling |
| Thrombomodulin | THBD | NM_000361 | 2.3 ± 0.11 | B/D | Anticoagulation |
| Thyroid hormone receptor interactor 7 | TRIP7 | L40357 | 2.5 ± 0.67 | C | Thyroid hormone signal transduction |
| Tissue factor | F3 | NM_001993 | 0.4 ± 0.03 | B/D | Extrinsic coagulation |
| Tissue factor pathway inhibitor 1 | TFPI | NM_006287 | 1.8 ± 0.77 | D | Extrinsic coagulation |
| Translation elongation factor 1 α 2 | EEF1A2 | NM_001958 | 1.1 ± 0.05 | F | Translation |
| α-Tubulin | TUBA3 | NM_006009 | 1.2 ± 0.04 | F | Intracellular transport |
| VCAM | VCAM1 | NM_001078 | 0.6 ± 0.02 | B/D | Leukocyte adhesion receptor |
| Vinculin | VCL | NM_003373 | 1.6 ± 0.63 | D | Cytoskeletal/adherens junction protein |
| Von Willebrand Factor | VWF | NM_000552 | 2.4 ± 0.18 | D | Platelet adhesion (hemostasis) |
| Protein name . | Gene name . | GenBank* . | Ratio ± SEM† . | Cat‡ . | Protein function . |
|---|---|---|---|---|---|
| β-Actin | ACTB | NM_001101 | 1.1 ± 0.07 | F | Cytoskeletal protein |
| Activin βA | INHBA | NM_002192 | 3.1 ± 1.29 | E | Vascular growth factor |
| ALL1-fused gene from chromosome 1q | AF1Q | NM_006818 | 1.4 ± 0.43 | A | Unknown |
| Amyloid β A4 precursor protein | APP | NM_000484 | 2.3 ± 0.49 | D | Alzheimer disease/hemostasis |
| Annexin II | ANXA2 | NM_004039 | 1.2 ± 0.06 | D | Membrane-binding protein |
| Annexin V | ANXA5 | NM_001154 | 2.2 ± 0.14 | D | Anticoagulant protein |
| ApoL1 | APOL1 | NM_003661 | 2.0 ± 0.19 | C | HDL-associated plasma protein |
| ApoL2 | APOL2 | NM_030882 | 1.7 ± 0.42 | C | Homolog of ApoL1 |
| ApoL3 (CG12_1) | APOL3 | NM_014349 | 3.9 ± 1.40 | C | Homolog of ApoL1 |
| AT7_4_3 | No match | 0.4 ± 0.10 | C | Unknown | |
| Biglycan | BGN | NM_001711 | 1.3 ± 0.41 | D | Extracellular matrix constituent |
| Caveolin 1 | CAV1 | NM_01753 | 0.6 ± 0.13 | D | Main component of caveolae |
| Claudin 5 | CLDN5 | NM_003277 | 2.1 ± 0.43 | A | Tight junction protein |
| Cockayne syndrome, type I | CKN1 | NM_000082 | 5.7 ± 2.35 | C | RNA polymerase II transcription |
| Connexin 40 | GJA5 | NM_005266 | 3.2 ± 0.93 | A | Gap junction protein |
| Cyclin-dependent kinase inhibitor 1A (p21) | CDKN1A | NM_000389 | 1.7 ± 0.62 | A | Cell-cycle regulation |
| Cytochrome P450 1B1 | CYP1B1 | NM_000104 | 26.9 ± 0.08 | A | Hormone metabolism |
| Dermatan sulphate proteoglycan 3 | DSPG3 | NM_004950 | 0.7 ± 0.05 | D | Extracellular matrix constituent |
| Diaphorase | DIA4/NQO1 | NM_000903 | 10.9 ± 5.93 | A | Detoxification/nitric oxide synthesis |
| DKFZp564F053 cDNA clone | AA166719 | 3.7 ± 1.24 | C | Unknown | |
| Early growth response 1 | EGR1 | NM_001964 | 1.2 ± 0.17 | B/D | Transcription factor |
| Endothelial protein C receptor | PROCR | NM_006404 | 1.1 ± 0.24 | D | Anticoagulation |
| eNOS | NOS3 | NM_000603 | 4.0 ± 0.73 | B/D | Nitric oxide synthesis |
| EST 15 | R96525 | 1.7 ± 0.25 | C | Unknown | |
| EST 23 | AI632668 | 1.2 ± 0.30 | C | Unknown | |
| EST 35 | AA455259 | 1.8 ± 0.21 | C | Unknown | |
| EST 41 | AI140281 | 1.7 ± 0.42 | C | Unknown | |
| Ferritin, heavy polypeptide | FTH1 | NM_002032 | 2.5 ± 0.48 | C | Intracellular iron storage |
| Ferritin, light polypeptide | FTL | NM_000146 | 2.0 ± 0.12 | A | Intracellular iron storage |
| Fibronectin 1 | FN1 | X02761 | 3.9 ± 0.59 | D | Extracellular matrix protein |
| G1 to S phase transition 1 | GSPT1 | NM_002094 | 0.5 ± 0.08 | C | Cell-cycle regulation |
| Galectin 8 | LGALS8 | NM_006499 | 4.3 ± 0.73 | C | Carbohydrate binding protein |
| GAPDH | GAPD | NM_002046 | 1.0 ± 0.00 | F | Carbohydrate metabolism |
| Hypothetical protein | NM_014108 | 2.3 ± 1.00 | E | Unknown | |
| Hypothetical protein | FLJ23514 | NM_021827 | 0.6 ± 0.09 | C | Unknown |
| Hypothetical protein | FLJ20003 | N47844 | 1.8 ± 0.30 | C | Unknown |
| Hypothetical protein | T80319 | 2.9 ± 0.58 | A | Unknown | |
| Hypothetical protein | BC004930 | 0.4 ± 0.23 | C | Unknown | |
| Interleukin 8 | IL8 | M28130 | 1.0 ± 0.16 | D/E | Inflammatory cytokine |
| LOX-1 | OLR1 | NM_079167 | 1.0 ± 0.45 | D | Oxidized LDL internalization |
| Lung Krüppel-like factor | KLF2 | NM_016270 | 4.9 ± 1.74 | A | Transcription factor |
| Matrix Gla protein | MGP | NM_000900 | 3.7 ± 1.21 | E | Inhibits extracellular matrix calcification |
| MnSOD | SOD2 | NM_000636 | 1.1 ± 0.61 | B/D | Free radical scavenging |
| Multimerin | MMRN | NM_007351 | 2.0 ± 0.54 | D | Hemostasis |
| PAI-1 | SERPINE1 | NM_000602 | 1.4 ± 0.71 | D | Fibrinolysis/proliferation/migration |
| PECAM-1 | PECAM1 | NM_000442 | 2.1 ± 0.37 | D | (Leukocyte) adhesion receptor |
| Prefoldin 2 | PFDN2 | NM_012394 | 2.2 ± 0.44 | C | Membrane-binding protein/autoantigen |
| Protease nexin 1 | GDN | M17783 | 6.4 ± 3.18 | D | Serine protease inhibitor |
| Rabkinesin 6 | RAB6KIFL | NM_005733 | 3.0 ± 0.55 | C | Intracellular transport/cell division |
| Ras-related C3 botulinum toxin substrate 3 | RAC3 | NM_005052 | 1.6 ± 0.07 | C | Ras-related GTPase |
| Regulator of G protein signaling | RGS5 | R38334 | 1.4 ± 0.77 | C | GTPase activator |
| 28S ribosomal RNA | M11167 | 0.9 ± 0.19 | F | Translation | |
| Ribosomal protein L30 | RPL30 | NM_000989 | 1.1 ± 0.16 | F | Translation |
| Ribosomal protein S11 | RPS11 | NM_001015 | 0.7 ± 0.13 | C | Translation |
| Solute carrier family 7, member 11 | SLC7A11 | NM_014331 | 2.1 ± 0.06 | A | Amino acid transporter |
| Spermidine/spermine N1-acetyltransferase | SAT | NM_002970 | 1.0 ± 0.12 | A | Polyamine metabolism |
| Stromal cell-derived factor 2 | SDF2 | AA343837 | 2.4 ± 0.20 | C | Secretory protein |
| Thioredoxin reductase 1 | TXNRD1 | NM_003330 | 2.0 ± 0.08 | A | Intracellular redox control |
| Thrombin receptor 1 | F2R | NM_001992 | 2.0 ± 0.18 | D | Mitogenic signaling |
| Thrombomodulin | THBD | NM_000361 | 2.3 ± 0.11 | B/D | Anticoagulation |
| Thyroid hormone receptor interactor 7 | TRIP7 | L40357 | 2.5 ± 0.67 | C | Thyroid hormone signal transduction |
| Tissue factor | F3 | NM_001993 | 0.4 ± 0.03 | B/D | Extrinsic coagulation |
| Tissue factor pathway inhibitor 1 | TFPI | NM_006287 | 1.8 ± 0.77 | D | Extrinsic coagulation |
| Translation elongation factor 1 α 2 | EEF1A2 | NM_001958 | 1.1 ± 0.05 | F | Translation |
| α-Tubulin | TUBA3 | NM_006009 | 1.2 ± 0.04 | F | Intracellular transport |
| VCAM | VCAM1 | NM_001078 | 0.6 ± 0.02 | B/D | Leukocyte adhesion receptor |
| Vinculin | VCL | NM_003373 | 1.6 ± 0.63 | D | Cytoskeletal/adherens junction protein |
| Von Willebrand Factor | VWF | NM_000552 | 2.4 ± 0.18 | D | Platelet adhesion (hemostasis) |
GenBank accession numbers for access to mRNA sequence or spotted cDNA fragment.
Ratios of the expression level in flow-exposed cultures over static cultures, as determined by microarray hybridization, are expressed as the mean of 3 independent 7-day shear-stress experiments ± SEM.
Genes on the custom microarray are organized in the following categories (Cat): (A) 12 shear-stress–responsive genes identified in this study, (B) 10 established shear-stress–responsive genes,7,17 (C) 106 TNF-α–responsive genes,6 (D) prominent endothelial (-specific) genes, (E) 40 smooth muscle activation–specific genes,24 and (F) control genes for normalization purposes. The sets of TNF-α–responsive endothelial genes and activated SMC genes were identified in previous studies from our group using differential display RT-PCR (DD/RT-PCR).6,24 The recently available University of California Santa Cruz (UCSC) draft version of the human genome was used to annotate those differential display (DD) fragments that had not yet been mapped to a named gene.44