Abstract
Endothelial dysfunction has been associated with a host of cardiovascular diseases and is thought to be an important contributor to many of them. Exercise training is a potent nonpharmacological modality to improve endothelial dysfunction. It is thought that the elevated intravascular shear stress is what leads to exercise-induced improvements in endothelial function. Microarray studies show that the gene expression profile of endothelial cells is dramatically altered by high physiological levels of laminar shear stress. Overwhelmingly, the genetic program of protein expression in response to in vitro laminar shear stress is vasoprotective and atheroprotective. There are three purposes of this chapter: (1) to review endothelial dysfunction at the cellular level, (2) to describe the different types of shear stress to which endothelial cells are exposed and the methodology used to examine them; and (3) to specifically describe the effects of high physiological levels of laminar shear stress on the expression of genes and proteins directly related to endothelial health.
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- BAEC:
-
Bovine aortic endothelial cell
- BH4 :
-
Tetrahydrobiopterin
- cGMP:
-
Cyclic guanosine monophosphate
- COX:
-
Cyclooxygenase
- CVD:
-
Cardiovascular disease
- EC:
-
Endothelial cell
- ECE:
-
Endothelin converting enzyme
- eNOS:
-
Endothelial nitric oxide synthase
- ET-1:
-
Endothelin-1
- GPX:
-
Glutathione peroxidase
- HAEC:
-
Human aortic endothelial cell
- HCAEC:
-
Human coronary artery endothelial cell
- HMVEC:
-
Human microvessel endothelial cell
- HUAEC:
-
Human umbilical artery endothelial cell
- HUVEC:
-
Human umbilical vein endothelial cell
- ICAM-1:
-
Intracellular adhesion molecule-1
- IL-6:
-
Interlukin-6
- JAK-STAT:
-
Janus kinase-signal transducer and activator of transcription
- KLF2:
-
Krüppel-like factor 2
- LSS:
-
Laminar shear stress
- MCP:
-
Monocyte chemotactic protein 1
- miRNA:
-
Micro ribonucleic acid
- mRNA:
-
Messenger ribonucleic acid
- mtDNA:
-
Mitochondrial deoxribonucleic acid
- NADPH:
-
Nicotanimide adenine dinucleotide phosphate oxidase
- NF-κB:
-
Nuclear factor kappa B
- NO:
-
Nitric oxide
- NOS:
-
Nitric oxide synthase
- Nox:
-
Nicotanimide adenine dinucleotide phosphate oxidase
- Nrf2:
-
Nuclear factor erythroid 2-like-2
- P13k/Akt:
-
Phosphoinositide 3-kinase inhibitor/protein kinase B
- PG:
-
Prostaglandin
- PGC-1α:
-
Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha
- PGHS:
-
Prostaglandin G/H synthase
- PGI2 :
-
Prostaglandin-2
- PKA:
-
Protein Kinase A
- PTEN:
-
Phosphatase and tensin homolog
- ROS:
-
Reactive oxygen species
- Ser:
-
Serine
- SIRT1:
-
Sirtuin 1
- SOD:
-
Superoxide dismutase
- TNF-α:
-
Tumor necrosis factor-alpha
- Trx:
-
Thioredoxin
- VCAM-1:
-
Vascular cell adhesion molecule-1
References
Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980;288:373–6.
Panza JA, Quyyumi AA, Brush JE, Epstein SE. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med. 1990;323:22–7.
Yeboah J, Sutton-Tyrrell K, McBurnie MA, Burke GL, Herrington DM, Crouse JR. Association between brachial artery reactivity and cardiovascular disease status in an elderly cohort: the cardiovascular health study. Atherosclerosis. 2008;197:768–76.
Smith JJ, Kampine JP, editors. Circulatory physiology-the essentials. Baltimore: Lippincott Williams & Wilkins; 1990.
Malek AM, Alper SL, Izumo S. Hemodynamic shear stress and its role in atherosclerosis. JAMA. 1999;282:2035–42.
Taylor CA, Hughes TJ, Zarins CK. Effect of exercise on hemodynamic conditions in the abdominal aorta. J Vasc Surg. 1999;29:1077–89.
Wasserman SM, Topper JN. Adaptation of the endothelium to fluid flow: in vitro analyses of gene expression and in vivo implications. Vasc Med. 2004;9:35–45.
Gibbons GH, Dzau VJ. The emerging concept of vascular remodeling. N Engl J Med. 1994;330:1431–8.
Zarins CK, Zatina MA, Giddens DP, Ku DN, Glagov S. Shear stress regulation of artery lumen diameter in experimental atherogenesis. J Vasc Surg. 1987;5:413–20.
Barbee KA. Changes in surface topography in endothelial monolayers with time at confluence: influence on subcellular shear stress distribution due to flow. Biochem Cell Biol. 1995;73:501–5.
Reneman RS, Arts T, Hoeks AP. Wall shear stress—an important determinant of endothelial cell function and structure—in the arterial system in vivo. Discrepancies with theory. J Vasc Res. 2006;43:251–69.
Barakat AI, Lieu DK, Gojova A. Secrets of the code: do vascular endothelial cells use ion channels to decipher complex flow signals? Biomaterials. 2006;27:671–8.
Braddock M, Schwachtgen JL, Houston P, Dickson MC, Lee MJ, Campbell CJ. Fluid shear stress modulation of gene expression in endothelial cells. News Physiol Sci. 1998;13:241–6.
Fledderus JO, van Thienen JV, Boon RA, et al. Prolonged shear stress and KLF2 suppress constitutive proinflammatory transcription through inhibition of ATF2. Blood. 2007;109:4249–57.
Resnick N, Collins T, Atkinson W, Bonthron DT, Dewey Jr CF, Gimbrone Jr MA. Platelet-derived growth factor B chain promoter contains a cis-acting fluid shear-stress-responsive element. Proc Natl Acad Sci U S A. 1993;90:4591–5.
Shyy JY, Li YS, Lin MC, et al. Multiple cis-elements mediate shear stress-induced gene expression. J Biomech. 1995;28:1451–7.
Ohura N, Yamamoto K, Ichioka S, et al. Global analysis of shear stress-responsive genes in vascular endothelial cells. J Atheroscler Thromb. 2003;10:304–13.
Griendling KK, FitzGerald GA. Oxidative stress and cardiovascular injury: part I: basic mechanisms and in vivo monitoring of ROS. Circulation. 2003;108:1912–6.
Griendling KK, FitzGerald GA. Oxidative stress and cardiovascular injury: part II: animal and human studies. Circulation. 2003;108:2034–40.
dela Paz NG, D’Amore PA. Arterial versus venous endothelial cells. Cell Tissue Res. 2009;335:5–16.
Reinhart-King CA, Fujiwara K, Berk BC. Physiologic stress-mediated signaling in the endothelium. Methods Enzymol. 2008;443:25–44.
Jenny NS, Mann KG. Coagulation cascade: an overview. In: Loscalzo J, Schafer AI, editors. Thrombosis and hemorrhage. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2002. p. 1–21.
Palmer R, Ferrige AG, Monacada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987;327:524.
Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci U S A. 1987;84:9265–9.
Grubbs AL, Ergul A. A review of endothelin and hypertension in African-American individuals. Ethn Dis. 2001;11:741–8.
Balligand JL, Feron O, Dessy C. eNOS activation by physical forces: from short-term regulation of contraction to chronic remodeling of cardiovascular tissues. Physiol Rev. 2009;89:481–534.
Konishi M, Su C. Role of endothelium in dilator responses of spontaneously hypertensive rat arteries. Hypertension. 1983;5:881–6.
Lockette W, Otsuka Y, Carretero O. The loss of endothelium-dependent vascular relaxation in hypertension. Hypertension. 1986;8:II61–6.
Luscher TF, Raij L, Vanhoutte PM. Endothelium-dependent vascular responses in normotensive and hypertensive Dahl rats. Hypertension. 1987;9:157–63.
Panza JA, Casino PR, Kilcoyne CM, Quyyumi AA. Role of endothelium-derived nitric oxide in the abnormal endothelium-dependent vascular relaxation of patients with essential hypertension. Circulation. 1993;87:1468–74.
Taddei S, Virdis A, Ghiadoni L, Magagna A, Salvetti A. Cyclooxygenase inhibition restores nitric oxide activity in essential hypertension. Hypertension. 1997;29:274–9.
Calver A, Collier J, Moncada S, Vallance P. Effect of local intra-arterial NG-monomethyl-L-arginine in patients with hypertension: the nitric oxide dilator mechanism appears abnormal. J Hypertens. 1992;10:1025–31.
Sessa WC, Pritchard K, Seyedi N, Wang J, Hintze TH. Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression. Circ Res. 1994;74:349–53.
Woodman CR, Muller JM, Laughlin MH, Price EM. Induction of nitric oxide synthase mRNA in coronary resistance arteries isolated from exercise-trained pigs. Am J Physiol. 1997;273:H2575–9.
Indolfi C, Torella D, Coppola C, et al. Physical training increases eNOS vascular expression and activity and reduces restenosis after balloon angioplasty or arterial stenting in rats. Circ Res. 2002;91:1190–7.
Uematsu M, Ohara Y, Navas JP, et al. Regulation of endothelial cell nitric oxide synthase mRNA expression by shear stress. Am J Physiol. 1995;269:C1371–8.
Nishida K, Harrison DG, Navas JP, et al. Molecular cloning and characterization of the constitutive bovine aortic endothelial cell nitric oxide synthase. J Clin Invest. 1992;90:2092–6.
Ranjan V, Xiao Z, Diamond SL. Constitutive NOS expression in cultured endothelial cells is elevated by fluid shear stress. Am J Physiol. 1995;269:H550–5.
Woodman CR, Muller JM, Rush JW, Laughlin MH, Price EM. Flow regulation of ecNOS and Cu/Zn SOD mRNA expression in porcine coronary arterioles. Am J Physiol. 1999;276:H1058–63.
Woodman CR, Price EM, Laughlin MH. Shear stress induces eNOS mRNA expression and improves endothelium-dependent dilation in senescent soleus muscle feed arteries. J Appl Physiol. 2005;98:940–6.
Davis ME, Grumbach IM, Fukai T, Cutchins A, Harrison DG. Shear stress regulates endothelial nitric-oxide synthase promoter activity through nuclear factor kappaB binding. J Biol Chem. 2004;279:163–8.
Hay DC, Beers C, Cameron V, Thomson L, Flitney FW, Hay RT. Activation of NF-kappaB nuclear transcription factor by flow in human endothelial cells. Biochim Biophys Acta. 2003;1642:33–44.
Park JY, Farrance IK, Fenty NM, et al. NFKB1 promoter variation implicates shear-induced NOS3 gene expression and endothelial function in prehypertensives and stage I hypertensives. Am J Physiol Heart Circ Physiol. 2007;293:H2320–7.
Lin Z, Kumar A, SenBanerjee S, et al. Kruppel-like factor 2 (KLF2) regulates endothelial thrombotic function. Circ Res. 2005;96:e48–57.
SenBanerjee S, Lin Z, Atkins GB, et al. KLF2 Is a novel transcriptional regulator of endothelial proinflammatory activation. J Exp Med. 2004;199:1305–15.
Boo YC, Hwang J, Sykes M, et al. Shear stress stimulates phosphorylation of eNOS at Ser(635) by a protein kinase A-dependent mechanism. Am J Physiol Heart Circ Physiol. 2002;283:H1819–28.
Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R, Zeiher AM. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature. 1999;399:601–5.
Fleming I, Fisslthaler B, Dixit M, Busse R. Role of PECAM-1 in the shear-stress-induced activation of Akt and the endothelial nitric oxide synthase (eNOS) in endothelial cells. J Cell Sci. 2005;118:4103–11.
Tayeh MA, Marletta MA. Macrophage oxidation of L-arginine to nitric oxide, nitrite, and nitrate. Tetrahydrobiopterin is required as a cofactor. J Biol Chem. 1989;264:19654–8.
Stuehr DJ, Kwon NS, Nathan CF. FAD and GSH participate in macrophage synthesis of nitric oxide. Biochem Biophys Res Commun. 1990;168:558–65.
Stuehr DJ, Cho HJ, Kwon NS, Weise MF, Nathan CF. Purification and characterization of the cytokine-induced macrophage nitric oxide synthase: an FAD- and FMN-containing flavoprotein. Proc Natl Acad Sci U S A. 1991;88:7773–7.
Palmer RMJMS. A novel citrulline-forming enzyme implicated in the formation of nitric oxide by vascular endothelial cells. Biochem Biophys Res Commun. 1989;158:348–52.
Landmesser U, Dikalov S, Price SR, et al. Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension. J Clin Invest. 2003;111:1201–9.
Laursen JB, Somers M, Kurz S, et al. Endothelial regulation of vasomotion in apoE-deficient mice: implications for interactions between peroxynitrite and tetrahydrobiopterin. Circulation. 2001;103:1282–8.
Cai S, Khoo J, Mussa S, Alp NJ, Channon KM. Endothelial nitric oxide synthase dysfunction in diabetic mice: importance of tetrahydrobiopterin in eNOS dimerisation. Diabetologia. 2005;48:1933–40.
Widder JD, Chen W, Li L, et al. Regulation of tetrahydrobiopterin biosynthesis by shear stress. Circ Res. 2007;101:830–8.
Yanagisawa M, Kurihara H, Kimura S, et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988;332:411–5.
Cardillo C, Kilcoyne CM, Cannon 3rd RO, Panza JA. Interactions between nitric oxide and endothelin in the regulation of vascular tone of human resistance vessels in vivo. Hypertension. 2000;35:1237–41.
de Nucci G, Thomas R, D’Orleans-Juste P, et al. Pressor effects of circulating endothelin are limited by its removal in the pulmonary circulation and by the release of prostacyclin and endothelium-derived relaxing factor. Proc Natl Acad Sci U S A. 1988;85:9797–800.
Schiffrin EL. Endothelin: potential role in hypertension and vascular hypertrophy. Hypertension. 1995;25:1135–43.
Campia U, Cardillo C, Panza JA. Ethnic differences in the vasoconstrictor activity of endogenous endothelin-1 in hypertensive patients. Circulation. 2004;109:3191–5.
Schiffrin EL. Role of endothelin-1 in hypertension and vascular disease. Am J Hypertens. 2001;14:83S–9.
Modesti PA, Cecioni I, Costoli A, Poggesi L, Galanti G, Serneri GG. Renal endothelin in heart failure and its relation to sodium excretion. Am Heart J. 2000;140:617–22.
Krum H, Viskoper RJ, Lacourciere Y, Budde M, Charlon V. The effect of an endothelin-receptor antagonist, bosentan, on blood pressure in patients with essential hypertension. Bosentan Hypertension Investigators. N Engl J Med. 1998;338:784–90.
Sharefkin JB, Diamond SL, Eskin SG, McIntire LV, Dieffenbach CW. Fluid flow decreases preproendothelin mRNA levels and suppresses endothelin-1 peptide release in cultured human endothelial cells. J Vasc Surg. 1991;14:1–9.
Masatsugu K, Itoh H, Chun TH, et al. Shear stress attenuates endothelin and endothelin-converting enzyme expression through oxidative stress. Regul Pept. 2003;111:13–9.
Malek AM, Zhang J, Jiang J, Alper SL, Izumo S. Endothelin-1 gene suppression by shear stress: pharmacological evaluation of the role of tyrosine kinase, intracellular calcium, cytoskeleton, and mechanosensitive channels. J Mol Cell Cardiol. 1999;31:387–99.
Morawietz H, Talanow R, Szibor M, et al. Regulation of the endothelin system by shear stress in human endothelial cells. J Physiol. 2000;525(Pt 3):761–70.
Hinz B, Brune K. Cyclooxygenase-2–10 years later. J Pharmacol Exp Ther. 2002;300:367–75.
Vane JR, Botting RM. Pharmacodynamic profile of prostacyclin. Am J Cardiol. 1995;75:3A–10.
Herschman HR. Function and regulation of prostaglandin synthase 2. Adv Exp Med Biol. 1999;469:3–8.
Topper JN, Cai J, Falb D, Gimbrone Jr MA. Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli: cyclooxygenase-2, manganese superoxide dismutase, and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress. Proc Natl Acad Sci U S A. 1996;93:10417–22.
Grabowski EF, Jaffe EA, Weksler BB. Prostacyclin production by cultured endothelial cell monolayers exposed to step increases in shear stress. J Lab Clin Med. 1985;105:36–43.
McCormick SM, Whitson PA, Wu KK, McIntire LV. Shear stress differentially regulates PGHS-1 and PGHS-2 protein levels in human endothelial cells. Ann Biomed Eng. 2000;28:824–33.
Huie RE, Padmaja S. The reaction of no with superoxide. Free Radic Res Commun. 1993;18:195–9.
Knowles RG, Moncada S. Nitric oxide synthases in mammals. Biochem J. 1994;298(Pt 2):249–58.
Ushio-Fukai M, Alexander RW, Akers M, Griendling KK. p38 Mitogen-activated protein kinase is a critical component of the redox-sensitive signaling pathways activated by angiotensin II. Role in vascular smooth muscle cell hypertrophy. J Biol Chem. 1998;273:15022–9.
Di Castro S, Scarpino S, Marchitti S, et al. Differential modulation of uncoupling protein 2 in kidneys of stroke-prone spontaneously hypertensive rats under high-salt/low-potassium diet. Hypertension. 2013;61:534–41.
Glassman SJ. Vitiligo, reactive oxygen species and T-cells. Clin Sci (Lond). 2011;120:99–120.
Jung O, Schreiber JG, Geiger H, Pedrazzini T, Busse R, Brandes RP. gp91phox-containing NADPH oxidase mediates endothelial dysfunction in renovascular hypertension. Circulation. 2004;109:1795–801.
Kagota S, Tada Y, Kubota Y, et al. Peroxynitrite is Involved in the dysfunction of vasorelaxation in SHR/NDmcr-cp rats, spontaneously hypertensive obese rats. J Cardiovasc Pharmacol. 2007;50:677–85.
Zalba G, Beaumont FJ, San Jose G, et al. Vascular NADH/NADPH oxidase is involved in enhanced superoxide production in spontaneously hypertensive rats. Hypertension. 2000;35:1055–61.
Montezano AC, Touyz RM. Reactive oxygen species, vascular Noxs, and hypertension: focus on translational and clinical research. Antioxid Redox Signal. 2014;20:164–82.
Lassègue B, San Martín A, Griendling KK. Biochemistry, physiology, and pathophysiology of NADPH oxidases in the cardiovascular system. Circ Res. 2012;110:1364–90.
Ago T, Kitazono T, Ooboshi H, et al. Nox4 as the major catalytic component of an endothelial NAD(P)H oxidase. Circulation. 2004;109:227–33.
Goettsch C, Goettsch W, Muller G, Seebach J, Schnittler HJ, Morawietz H. Nox4 overexpression activates reactive oxygen species and p38 MAPK in human endothelial cells. Biochem Biophys Res Commun. 2009;380:355–60.
Babior BM. NADPH oxidase. Curr Opin Immunol. 2004;16:42–7.
Rey FE, Cifuentes ME, Kiarash A, Quinn MT, Pagano PJ. Novel competitive inhibitor of NAD(P)H oxidase assembly attenuates vascular O(2)(-) and systolic blood pressure in mice. Circ Res. 2001;89:408–14.
Guimaraes DD, Carvalho CC, Braga VA. Scavenging of NADPH oxidase-derived superoxide anions improves depressed baroreflex sensitivity in spontaneously hypertensive rats. Clin Exp Pharmacol Physiol. 2012;39:373–8.
Gavazzi G, Banfi B, Deffert C, et al. Decreased blood pressure in NOX1-deficient mice. FEBS Lett. 2006;580:497–504.
Dikalov SI, Dikalova AE, Bikineyeva AT, Schmidt HH, Harrison DG, Griendling KK. Distinct roles of Nox1 and Nox4 in basal and angiotensin II-stimulated superoxide and hydrogen peroxide production. Free Radic Biol Med. 2008;45:1340–51.
Mohan S, Mohan N, Sprague EA. Differential activation of NF-kappa B in human aortic endothelial cells conditioned to specific flow environments. Am J Physiol. 1997;273:C572–8.
Mohan S, Mohan N, Valente AJ, Sprague EA. Regulation of low shear flow-induced HAEC VCAM-1 expression and monocyte adhesion. Am J Physiol. 1999;276:C1100–7.
Dai G, Kaazempur-Mofrad MR, Natarajan S, et al. Distinct endothelial phenotypes evoked by arterial waveforms derived from atherosclerosis-susceptible and -resistant regions of human vasculature. Proc Natl Acad Sci U S A. 2004;101:14871–6.
Duerrschmidt N, Stielow C, Muller G, Pagano PJ, Morawietz H. NO-mediated regulation of NAD(P)H oxidase by laminar shear stress in human endothelial cells. J Physiol. 2006;576:557–67.
White SJ, Hayes EM, Lehoux S, Jeremy JY, Horrevoets AJ, Newby AC. Characterization of the differential response of endothelial cells exposed to normal and elevated laminar shear stress. J Cell Physiol. 2011;226:2841–8.
Goettsch C, Goettsch W, Brux M, et al. Arterial flow reduces oxidative stress via an antioxidant response element and Oct-1 binding site within the NADPH oxidase 4 promoter in endothelial cells. Basic Res Cardiol. 2011;106:551–61.
De Keulenaer GW, Chappell DC, Ishizaka N, Nerem RM, Alexander RW, Griendling KK. Oscillatory and steady laminar shear stress differentially affect human endothelial redox state: role of a superoxide-producing NADH oxidase. Circ Res. 1998;82:1094–101.
Rueckschloss U, Galle J, Holtz J, Zerkowski HR, Morawietz H. Induction of NAD(P)H oxidase by oxidized low-density lipoprotein in human endothelial cells: antioxidative potential of hydroxymethylglutaryl coenzyme A reductase inhibitor therapy. Circulation. 2001;104:1767–72.
Rueckschloss U, Duerrschmidt N, Morawietz H. NADPH oxidase in endothelial cells: impact on atherosclerosis. Antioxid Redox Signal. 2003;5:171–80.
Feairheller DL, Park JY, Rizzo V, Kim B, Brown MD. Racial differences in the responses to shear stress in human umbilical vein endothelial cells. Vasc Health Risk Manag. 2011;7:425–31.
Macmillan-Crow LA, Cruthirds DL. Invited review: manganese superoxide dismutase in disease. Free Radic Res. 2001;34:325–36.
Harrison DG, Widder J, Grumbach I, Chen W, Weber M, Searles C. Endothelial mechanotransduction, nitric oxide and vascular inflammation. J Intern Med. 2006;259:351–63.
Kelner MJ, Montoya MA. Structural organization of the human glutathione reductase gene: determination of correct cDNA sequence and identification of a mitochondrial leader sequence. Biochem Biophys Res Commun. 2000;269:366–8.
Lundberg M, Johansson C, Chandra J, et al. Cloning and expression of a novel human glutaredoxin (Grx2) with mitochondrial and nuclear isoforms. J Biol Chem. 2001;276:26269–75.
Wang J, Pan S, Berk BC. Glutaredoxin mediates Akt and eNOS activation by flow in a glutathione reductase-dependent manner. Arterioscler Thromb Vasc Biol. 2007;27:1283–8.
Spyrou G, Enmark E, Miranda-Vizuete A, Gustafsson J. Cloning and expression of a novel mammalian thioredoxin. J Biol Chem. 1997;272:2936–41.
Altschmied J, Haendeler J. Thioredoxin-1 and endothelial cell aging: role in cardiovascular diseases. Antioxid Redox Signal. 2009;11:1733–40.
Gasdaska PY, Berggren MM, Berry MJ, Powis G. Cloning, sequencing and functional expression of a novel human thioredoxin reductase. FEBS Lett. 1999;442:105–11.
Miranda-Vizuete A, Damdimopoulos AE, Pedrajas JR, Gustafsson JA, Spyrou G. Human mitochondrial thioredoxin reductase cDNA cloning, expression and genomic organization. Eur J Biochem. 1999;261:405–12.
Koenig W, Sund M, Frohlich M, et al. C-Reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992. Circulation. 1999;99:237–42.
Holmgren A, Bjornstedt M. Thioredoxin and thioredoxin reductase. Methods Enzymol. 1995;252:199–208.
Watabe S, Hiroi T, Yamamoto Y, et al. SP-22 is a thioredoxin-dependent peroxide reductase in mitochondria. Eur J Biochem. 1997;249:52–60.
Knoops B, Clippe A, Bogard C, et al. Cloning and characterization of AOEB166, a novel mammalian antioxidant enzyme of the peroxiredoxin family. J Biol Chem. 1999;274:30451–8.
Valle I, Alvarez-Barrientos A, Arza E, Lamas S, Monsalve M. PGC-1alpha regulates the mitochondrial antioxidant defense system in vascular endothelial cells. Cardiovasc Res. 2005;66:562–73.
Groschner LN, Waldeck-Weiermair M, Malli R, Graier WF. Endothelial mitochondria—less respiration, more integration. Pflugers Arch. 2012;464:63–76.
Chen Z, Peng IC, Cui X, Li YS, Chien S, Shyy JY. Shear stress, SIRT1, and vascular homeostasis. Proc Natl Acad Sci U S A. 2010;107:10268–73.
Miller MW, Knaub LA, Olivera-Fragoso LF, et al. Nitric oxide regulates vascular adaptive mitochondrial dynamics. Am J Physiol Heart Circ Physiol. 2013;304:H1624–33.
Knaub LA, McCune S, Chicco AJ, et al. Impaired response to exercise intervention in the vasculature in metabolic syndrome. Diab Vasc Dis Res. 2013;10:222–38.
Quintero M, Colombo SL, Godfrey A, Moncada S. Mitochondria as signaling organelles in the vascular endothelium. Proc Natl Acad Sci U S A. 2006;103:5379–84.
Kluge MA, Fetterman JL, Vita JA. Mitochondria and endothelial function. Circ Res. 2013;112:1171–88.
Monsalve M, Borniquel S, Valle I, Lamas S. Mitochondrial dysfunction in human pathologies. Front Biosci. 2007;12:1131–53.
Liu Y, Zhao H, Li H, Kalyanaraman B, Nicolosi AC, Gutterman DD. Mitochondrial sources of H2O2 generation play a key role in flow-mediated dilation in human coronary resistance arteries. Circ Res. 2003;93:573–80.
Breton-Romero R, Acin-Perez R, Rodriguez-Pascual F, et al. Laminar shear stress regulates mitochondrial dynamics, bioenergetics responses and PRX3 activation in endothelial cells. Biochim Biophys Acta. 2014;1843:2403–13.
Kim B, Lee H, Kawata K, Park JY. Exercise-mediated wall shear stress increases mitochondrial biogenesis in vascular endothelium. PLoS One. 2014;9:e111409.
Collins AR, Lyon CJ, Xia X, et al. Age-accelerated atherosclerosis correlates with failure to upregulate antioxidant genes. Circ Res. 2009;104:e42–54.
Ai L, Rouhanizadeh M, Wu JC, et al. Shear stress influences spatial variations in vascular Mn-SOD expression: implication for LDL nitration. Am J Physiol Cell Physiol. 2008;294:C1576–85.
Sun D, Huang A, Yan EH, et al. Reduced release of nitric oxide to shear stress in mesenteric arteries of aged rats. Am J Physiol Heart Circ Physiol. 2004;286:H2249–56.
Dimmeler S, Hermann C, Galle J, Zeiher AM. Upregulation of superoxide dismutase and nitric oxide synthase mediates the apoptosis-suppressive effects of shear stress on endothelial cells. Arterioscler Thromb Vasc Biol. 1999;19:656–64.
Inoue N, Ramasamy S, Fukai T, Nerem RM, Harrison DG. Shear stress modulates expression of Cu/Zn superoxide dismutase in human aortic endothelial cells. Circ Res. 1996;79:32–7.
de Haan JB, Bladier C, Griffiths P, et al. Mice with a homozygous null mutation for the most abundant glutathione peroxidase, Gpx1, show increased susceptibility to the oxidative stress-inducing agents paraquat and hydrogen peroxide. J Biol Chem. 1998;273:22528–36.
Raes M, Michiels C, Remacle J. Comparative study of the enzymatic defense systems against oxygen-derived free radicals: the key role of glutathione peroxidase. Free Radic Biol Med. 1987;3:3–7.
Chrissobolis S, Didion SP, Kinzenbaw DA, et al. Glutathione peroxidase-1 plays a major role in protecting against angiotensin II-induced vascular dysfunction. Hypertension. 2008;51:872–7.
Takeshita S, Inoue N, Ueyama T, Kawashima S, Yokoyama M. Shear stress enhances glutathione peroxidase expression in endothelial cells. Biochem Biophys Res Commun. 2000;273:66–71.
Bautista LE. Inflammation, endothelial dysfunction, and the risk of high blood pressure: epidemiologic and biological evidence. J Hum Hypertens. 2003;17:223–30.
Sinisalo J, Paronen J, Mattila KJ, et al. Relation of inflammation to vascular function in patients with coronary heart disease. Atherosclerosis. 2000;149:403–11.
Yoshizumi M, Perrella MA, Burnett Jr JC, Lee ME. Tumor necrosis factor downregulates an endothelial nitric oxide synthase mRNA by shortening its half-life. Circ Res. 1993;73:205–9.
Verma S, Wang CH, Li SH, et al. A self-fulfilling prophecy: C-reactive protein attenuates nitric oxide production and inhibits angiogenesis. Circulation. 2002;106:913–9.
Vallance P, Collier J, Bhagat K. Infection, inflammation, and infarction: does acute endothelial dysfunction provide a link? Lancet. 1997;349:1391–2.
Huo Y, Ley K. Adhesion molecules and atherogenesis. Acta Physiol Scand. 2001;173:35–43.
Loetscher H, Pan YC, Lahm HW, et al. Molecular cloning and expression of the human 55 kd tumor necrosis factor receptor. Cell. 1990;61:351–9.
Schall TJ, Lewis M, Koller KJ, et al. Molecular cloning and expression of a receptor for human tumor necrosis factor. Cell. 1990;61:361–70.
Smith CA, Davis T, Anderson D, et al. A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins. Science. 1990;248:1019–23.
Madge LA, Pober JS. TNF signaling in vascular endothelial cells. Exp Mol Pathol. 2001;70:317–25.
De Palma C, Meacci E, Perrotta C, Bruni P, Clementi E. Endothelial nitric oxide synthase activation by tumor necrosis factor alpha through neutral sphingomyelinase 2, sphingosine kinase 1, and sphingosine 1 phosphate receptors: a novel pathway relevant to the pathophysiology of endothelium. Arterioscler Thromb Vasc Biol. 2006;26:99–105.
Zhang H, Park Y, Wu J, et al. Role of TNF-alpha in vascular dysfunction. Clin Sci (Lond). 2009;116:219–30.
Partridge J, Carlsen H, Enesa K, et al. Laminar shear stress acts as a switch to regulate divergent functions of NF-kappaB in endothelial cells. FASEB J. 2007;21:3553–61.
Yamawaki H, Lehoux S, Berk BC. Chronic physiological shear stress inhibits tumor necrosis factor-induced proinflammatory responses in rabbit aorta perfused ex vivo. Circulation. 2003;108:1619–25.
Surapisitchat J, Hoefen RJ, Pi X, Yoshizumi M, Yan C, Berk BC. Fluid shear stress inhibits TNF-alpha activation of JNK but not ERK1/2 or p38 in human umbilical vein endothelial cells: Inhibitory crosstalk among MAPK family members. Proc Natl Acad Sci U S A. 2001;98:6476–81.
Ni CW, Hsieh HJ, Chao YJ, Wang DL. Interleukin-6-induced JAK2/STAT3 signaling pathway in endothelial cells is suppressed by hemodynamic flow. Am J Physiol Cell Physiol. 2004;287:C771–80.
Zeng Y, Qiao Y, Zhang Y, Liu X, Wang Y, Hu J. Effects of fluid shear stress on apoptosis of cultured human umbilical vein endothelial cells induced by LPS. Cell Biol Int. 2005;29:932–5.
Segal SS, Duling BR. Conduction of vasomotor responses in arterioles: a role for cell-to-cell coupling? Am J Physiol. 1989;256:H838–45.
Chiu JJ, Chien S. Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives. Physiol Rev. 2011;91:327–87.
Poliseno L, Tuccoli A, Mariani L, et al. MicroRNAs modulate the angiogenic properties of HUVECs. Blood. 2006;108:3068–71.
Kuehbacher A, Urbich C, Zeiher AM, Dimmeler S. Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis. Circ Res. 2007;101:59–68.
Suarez Y, Fernandez-Hernando C, Pober JS, Sessa WC. Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells. Circ Res. 2007;100:1164–73.
Chan LS, Yue PY, Mak NK, Wong RN. Role of microRNA-214 in ginsenoside-Rg1-induced angiogenesis. Eur J Pharm Sci. 2009;38:370–7.
Davalos A, Goedeke L, Smibert P, et al. miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling. Proc Natl Acad Sci U S A. 2011;108:9232–7.
Menghini R, Casagrande V, Cardellini M, et al. MicroRNA 217 modulates endothelial cell senescence via silent information regulator 1. Circulation. 2009;120:1524–32.
Weber M, Baker MB, Moore JP, Searles CD. MiR-21 is induced in endothelial cells by shear stress and modulates apoptosis and eNOS activity. Biochem Biophys Res Commun. 2010;393:643–8.
Holliday-Ankeny CJ, Ankeny RF, Ferdous Z, Nerem RMHJ, Shear- and side-dependent microRNAs and messenger RNAs in aortic valvular endothelium. QScience Proc. 2012;56:60.
Yeboah J, Crouse JR, Hsu FC, Burke GL, Herrington DM. Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: the Cardiovascular Health Study. Circulation. 2007;115:2390–7.
Chen BP, Li YS, Zhao Y, et al. DNA microarray analysis of gene expression in endothelial cells in response to 24-h shear stress. Physiol Genomics. 2001;7:55–63.
Wei P, Milbauer LC, Enenstein J, Nguyen J, Pan W, Hebbel RP. Differential endothelial cell gene expression by African Americans versus Caucasian Americans: a possible contribution to health disparity in vascular disease and cancer. BMC Med. 2011;9:2.
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Brown, M.D., Park, JY. (2015). Effects of In Vitro Laminar Shear Stress as an Exercise Mimetic on Endothelial Cell Health. In: Pescatello, L. (eds) Effects of Exercise on Hypertension. Molecular and Translational Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-17076-3_7
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