Microcirculation as a Target for the Anti-inflammatory Properties of Statins

REFERENCES

• Amin-Hanjani S, Stagliano NE, Yamada M, Huang PL, Liao JK, Moskowitz MA. (2001). Mevastatin, an HMG-CoA reductase inhibitor, reduces stroke dam-age and upregulates endothelial nitric oxide syn-thase in mice. Stroke 32:980–986.
   PubMed Web of Science ®Google Scholar
• Asahara T, Masuda H, Takahashi T, Kalka C, Pas-tore C, Silver M, Kearne M, Magner M, Isner JM. (1999). Bone marrow origin of endothelial progeni-tor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 85:221–228.
   PubMed Web of Science ®Google Scholar
• Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner ym. (1997). Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964–967.
   PubMed Web of Science ®Google Scholar
• Bickel C, Rupprecht HJ, Blankenberg S, Espiniola-Klein C, Schlitt A, Rippin G, Hafner G, Treude R, Othrnan H, Hofmann KP, Meyer J. (2002). Relation of markers of inflammation (C-reactive protein, fi-brinogen, von Willebrand factor, and leukocyte count) and statin therapy to long-term mortality in patients with angiographically proven coronary ar-tery disease. Am J Cardiol 89:901–908.
   PubMed Web of Science ®Google Scholar
• Bienvenu K, Granger DN. (1993). Molecular deter-minants of shear rate-dependent leukocyte adhesion in postcapillary venules. Am J Physiol 264:H1504–H1508.
   Google Scholar
• Bitterman H, Aoki N, Lefer AM. (1998). Anti-shock effects of human superoxide dismutase in splanchnic artery occlusion (SAO) shock. Proc Soc Exp Biol Med 188:265–271.
   Google Scholar
• Blake GJ, Ridker PM. (2000). Are statins anti-inflammatory? Curr Control Trials Cardiovasc Med 1:161–165.
   PubMedGoogle Scholar
• Blake GJ, Ridker PM. (2001). Novel clinical mark-ers of vascular wall inflammation. Circ Res 89:763–771.
   PubMed Web of Science ®Google Scholar
• Booth G, Stalker TJ, Lefer AM, Scalia R. (2002). Mechanisms of amelioration of glucose-induced en-dothelial dysfunction following inhibition of protein kinase C in vivo. Diabetes 51:1556–1564.
   PubMed Web of Science ®Google Scholar
• Brouet A, Sonveaux P, Dessy C, Moniotte S, BAH - gand JL, Feron O. (2001). Hsp90 and caveolin are key targets for the proangiogenic nitric oxide-mediated effects of statins. Circ Res 89:866–873.
   PubMed Web of Science ®Google Scholar
• Crosby JR, Kaminski WE, Schatteman G, Martin PJ, Raines EW, Seifert RA, Bowen-Pope DF. (2000). Endothelial cells of hematopoietic origin make a sig- nificant contribution to adult blood vessel forma-tion. Circ Res 87:728–730.
   PubMed Web of Science ®Google Scholar
• Davenpeck KL, Gauthier TW, Lefer AM. (1994). Inhibition of endothelial-derived nitric oxide pro-motes P-selectin expression and actions in the rat microcirculation. Gastroenterology 107:1050–1058.
   PubMed Web of Science ®Google Scholar
• De Caterina R, Libby P, Peng FIB, Thannickal VJ, Rajavashisth TB, Girnbrone MAJ, Shin WS, Liao JK. (1995). Nitric oxide decreases cytokine-induced en-dothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and Proinflarnrnatory cytokines. J Clin Invest 96:60–68.
   Google Scholar
• Dirnrneler S, Aicher A, Vasa M, Mildner-Rihm C, Adler K, Tiemann M, Rutten H, Fichtlscherer S, Martin H, Zeiher AM. (2001). HVIG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. J Clin Invest 108:391–397.
   Google Scholar
• Dirnrneler S, Fleming I, Fisslthaler B, Hermann C, Busse R, Zeiher AM. (1999). Activation of nitric ox-ide synthase in endothelial cells by Akt- dependent Phosphorylation. Nature 399:601–605.
   Google Scholar
• Endres M, Laufs U, Huang Z, Nakamura T, Huang P, Moskowitz MA, Liao JK. (1998). Stroke protec-tion by 3 -hydroxy-3 -methylglutaryl (HMG) -CoA reductase inhibitors mediated by endothelial nitric oxide synthase. Proc Natl Acad Sci USA 95:8880–8885.
   PubMed Web of Science ®Google Scholar
• Feron O, Dessy C, Desager JP, Balligand JL. (2001). Hydroxy-methylglutaryl-coenzyme A reductase in-hibition promotes endothelial nitric oxide synthase activation through a decrease in caveolin abun-dance. Circulation 103:113–118.
   PubMed Web of Science ®Google Scholar
• Fries JW, Williams AJ, Atkins RC, Newman W, Lip-scomb MF, Collins T. (1993). Expression of VCA1VI-1 and E-selectin in an in vivo model of en-dothelial activation. Am J Pathol 143:725–737.
   PubMed Web of Science ®Google Scholar
• Fulton D, Grafton JP, McCabe TJ, Fontana J, Fujio Y, Walsh K, Franke TF, Papapetropoulos A, Sessa WC. (1999). Regulation of endothelium-derived ni-tric oxide production by the protein kinase Akt. Na-ture 399:597–601.
   PubMed Web of Science ®Google Scholar
• Furchgott RF, Vanhoutte PM. (1989). Endothe-lium-derived relaxing and contracting factors. FASER J 3:2007–2018.
   PubMed Web of Science ®Google Scholar
• Garcia-Cardena G, Fan R, Shah V, Sorrentino R, Cirino G, Papapetropoulos A, Sessa WC. (1998). Dynamic activation of endothelial nitric oxide syn-thase by Hsp90. Nature 392:821–824.
   PubMed Web of Science ®Google Scholar
• Garcia-Cardena G, Oh P, Liu J, Schnitzer JE, Sessa WC. (1996). Targeting of nitric oxide synthase to endothelial cell caveolae via palrnitoylation: impli-cations for nitric oxide signaling. Proc Natl Acad Sci USA 93:6448–6453.
   PubMed Web of Science ®Google Scholar
• Gauthier TW, Davenpeck KL, Lefer AM. (1994). Nitric oxide attenuates leukocyte-endothelial inter- action via P-selectin in splanchnic ischemia-reperfusion. Am J Physiol 267: G562–G568.
   Google Scholar
• Gotsch U, Jager U, Dominis M, Vestweber D. (1994). Expression of P-selectin on endothelial cells is upregulated by LPS and TNF-alpha in vivo. Cell Adhes Commun 2:7–14.
   PubMed Web of Science ®Google Scholar
• Granger DN, Benoit TN, Suzuki M, Grisham MB. (1989). Leukocyte adherence to venular endothe-lium during ischemia-reperfusion. Am J Physiol 257: G683–G688.
   PubMed Web of Science ®Google Scholar
• Granger DN, Kubes P. (1994). The microcirculation and inflammation: modulation of leukocyte-endothelial cell adhesion. J Leukoc Biol 55:662–675.
   PubMed Web of Science ®Google Scholar
• Gryglewski RJ, Palmer RM, Moncada S. (1986). Su-peroxide anion is involved in the breakdown of en-dothelium-derived vascular relaxing factor. Nature 320:454–456.
   PubMed Web of Science ®Google Scholar
• Hall A. (1992). Ras-related GTPases and the cyto-skeleton. Mol Biol Cell 3:475–479.
   Google Scholar
• Hall A. (1998). Rho GTPases and the actin cyto-skeleton. Science 279:509–514.
   Google Scholar
• Harrison DG. (1997). Cellular and molecular mechanisms of endothelial cell dysfunction. J Clin Invest 100:2153–2157.
   Google Scholar
• Harrison DG. (1994). Endothelial dysfunction in atherosclerosis. Basic Res Cardiol 89:87–102.
   Google Scholar
• Hernandez-Perera O, Perez-Sala D, Navarro-Antolin J, Sanchez-Pascuala R, Hernandez G, Diaz C, Lamas S. (1998). Effects of the 3 -hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvas-tatin and sirnvastatin, on the expression of endothe-lin-1 and endothelial nitric oxide synthase in vascu-lar endothelial cells. J Clin Invest 101:2711–2719.
   PubMed Web of Science ®Google Scholar
• Herrmann J, Lerman LO, Rodriguez-Porcel M, Hol-mes DR Jr, Richardson DM, Ritman EL, Lerman A. (2001). Coronary vasa vasorurn neovascularization precedes epicardial endothelial dysfunction in ex-perimental hypercholesterolemia. Cardiovasc Res 51:762–766.
   PubMed Web of Science ®Google Scholar
• Holm T, Andreassen AK, Ueland T, Kjekshus J, Fro-land SS, Kjekshus E, Simonsen S, Aukrust P, Gullestad L. (2001). Effect of pravastatin on plasma markers of inflammation and peripheral endothelial function in male heart transplant recipients. Am J Cardiol 87:815-818, A819.
   Google Scholar
• Hon i N, Wiest R, Groszinann RJ. (1998). Enhanced release of nitric oxide in response to changes in flow and shear stress in the superior mesenteric arteries of portal hypertensive rats. Hepatology 28:1467–1473.
   Google Scholar
• Joyce M, Kelly C, Winter D, Chen G, Leahy A, Bouchier-Hayes D. (2001). Pravastatin, a 3 -hy-droxy-3-methylglutaryl coenzyme A reductase in-hibitor, attenuates renal injury in an experimental model of ischemia-reperfusion. J Surg Res 101:79–84.
   Google Scholar
• Kaesemeyer WH, Caldwell RB, Huang J, Caldwell RW. (1999). Pravastatin sodium activates endothe-lial nitric oxide synthase independent of its choles-terol-lowering actions. J Am Coll Cardiol 33:234–241.
   PubMed Web of Science ®Google Scholar
• Kanwar S, Kubes P. (1995). Nitric oxide is an an-tiadhesive molecule for leukocytes. [80 refs]. New Horiz 3:93–104.
   PubMedGoogle Scholar
• Kashiwagi A, Asahina T, Nishio Y, Ikebuchi M, Tanaka Y, Kikkawa R, Shigeta Y. (1996). Glyca-tion, oxidative stress, and scavenger activity: glucose metabolism and radical scavenger dysfunction in endothelial cells. Diabetes 45 Suppl 3:S84–S86.
   Google Scholar
• Kimura M, Kurose I, Russell J, Granger DN. (1997). Effects of fluvastatin on leukocyte-endothelial cell adhesion in hypercholesterolemic rats. Arterioscler Thromb Vasc Biol 17:1521–1526.
   PubMed Web of Science ®Google Scholar
• Klein LM, Lavker RM, Matis WL, Murphy GF. (1989). Degranulation of human mast cells induces an endothelial antigen central to leukocyte adhesion. Proc Natl Acad Sci USA 86:8972–8976.
   PubMed Web of Science ®Google Scholar
• Koh KK. (2000). Effects of statins on vascular wall: vasomotor function, inflammation, and plaque sta-bility. Cardiovasc Res 47:648–657.
   PubMed Web of Science ®Google Scholar
• Kubes P, Suzuki M, Granger DN. (1991). Nitric ox-ide: an endogenous modulator of leukocyte adhe-sion. Proc Natl Acad Sci USA 88:4651–4655.
   Google Scholar
• Kureishi Y, Luo Z, Shiojirna I, Malik A, Fulton D, Lefer DJ, Sessa WC, Walsh K. (2000). The HMG-CoA reductase inhibitor sirnvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med 6:1004–1010.
   PubMed Web of Science ®Google Scholar
• Kurose I, Argenbright LW, Wolf R, Lianxi L, Granger DN. (1997). Ischemia/reperfusion-induced microvascular dysfunction: role of oxidants and lipid mediators. Am J Physiol 272:H2976–H2982.
   Google Scholar
• Kurose I, Wolf RE, Grisham MB, Granger DN. (1998 ) . Hypercholesterolemia enhances oxidant production in mesenteric venules exposed to isch-emia/reperfusion. Arterioscler Thromb Vasc Biol 18: 1583–1588.
   PubMed Web of Science ®Google Scholar
• Kwon HM, Sangiorgi G, Ritrnan EL, McKenna C, Holmes DRJ, Schwartz RS, Lerman A. (1998). En-hanced coronary vasa vasorurn neovascularization in experimental hypercholesterolemia. J Clin Invest 101:1551–1556.
   PubMed Web of Science ®Google Scholar
• Lamontagne D, Pohl U, Busse R. (1992). Mechani-cal deformation of vessel wall and shear stress de-termine the basal release of endothelium-derived re-laxing factor in the intact rabbit coronary vascular bed. Circ Res 70:123–130.
   PubMed Web of Science ®Google Scholar
• Laufs U, Fata VL, Liao JK. (1997). Inhibition of 3 -hydroxy-3 -methylglutaryl (HMG) -CoA reductase blocks hypoxia-mediated down-regulation of endo-thelial nitric oxide synthase. J Biol Chem 272: 31725–31729.
   PubMed Web of Science ®Google Scholar
• Laufs U, La Fata V, Plutzky J, Liao JK. (1998). Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation 97: 1129–1135.
   PubMed Web of Science ®Google Scholar
• Laufs U, Liao JK. (1998). Post-transcriptional regu-lation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. J Biol Chem 273:24266–24271.
   PubMed Web of Science ®Google Scholar
• Laufs U, Marra D, Node K, Liao JK. (1999). 3-Hy-droxy-3 -methylglutaryl-CoA reductase inhibitors attenuate vascular smooth muscle proliferation by preventing rho GTPase-induced down-regulation of p27(Kip1). J Biol Chem 274:21926–21931.
   PubMed Web of Science ®Google Scholar
• Lefer AM, Aoki N. (1990). Leukocyte-dependent and leukocyte-independent mechanisms of impair-ment of endothelium-mediated vasodilation. Blood Vessels 27:162–168.
   PubMedGoogle Scholar
• Lefer AM, Campbell B, Shin YK, Scalia R, Hayward R, Lefer DJ. (1999). Sirnvastatin preserves the isch-emic-reperfused myocardium in normocholesterol-emic rat hearts. Circulation 100:178–184.
   PubMed Web of Science ®Google Scholar
• Lefer AM, Lefer DJ. (1996). The role of nitric oxide and cell adhesion molecules on the microcirculation in ischaemia-reperfusion. Cardiovasc Res 32:743–751.
   PubMed Web of Science ®Google Scholar
• Lefer AM, Scalia R. (2001). Nitric Oxide in Inflam-mation. In: Physiology of Inflammation. (Ley K, Ed.) Oxford University Press, New York: p. 447–472.
   Google Scholar
• Lefer AM, Scalia R, Lefer DJ. (2001). Vascular ef-fects of HMG CoA-reductase inhibitors (statins) un-related to cholesterol lowering: new concepts for car-diovascular disease. Cardiovasc Res 49:281–287.
   PubMed Web of Science ®Google Scholar
• Lefer DJ, Jones SP, Girod WG, Baines A, Grisham MB, Cockrell AS, Huang PL, Scalia R. (1999). Leu-kocyte-endothelial cell interactions in nitric oxide synthase-deficient mice. Am J Physiol 276:H1943–H1950.
   Google Scholar
• Lefer DJ, Scalia R, Campbell B, Nossuli T, Hayward R, Salamon M, Grayson J, Lefer AM. (1997). Per-oxynitrite inhibits leukocyte-endothelial cell interac-tions and protects against ischemia-reperfusion in-jury in rats. J Clin Invest 99:684–691.
   PubMed Web of Science ®Google Scholar
• Lefer DJ, Scalia R, Jones SP, Sharp BR, Hoffmeyer MR, Farvid AR, Gibson MF, Lefer AM. (2001). HMG-CoA reductase inhibition protects the diabetic myocardium from ischemia-reperfusion injury. FASER J 15:1454–1456.
   Google Scholar
• Ley K. (2001). Leukocyte recruitment as seen by intravital microscopy. In: Physiology of Inflamma-tion. (Ley K, Ed.) Oxford University Press, New York: p. 303–337.
   Google Scholar
• Li X, Liu L, Tupper JC, Bannerman DD, Winn RK, Sebti SM, Hamilton AD, Harlan JM. (2002). Inhi-bition of protein geranylgeranylation and RhoA/ RhoA kinase pathway induces apoptosis in human endothelial cells. J Biol Chem 277:15309–15316.
   PubMed Web of Science ®Google Scholar
• Libby P. (2001). The pathogenesis of atherosclero-sis. In: Harrison's Principles of Internal Medicine, 15th ed. (Braunwald E, et al., Eds.)McGraw-Hill, New York.
   Google Scholar
• Llevadot J, Murasawa S, Kureishi Y, Uchida S, Ma-suda H, Kawarnoto A, Walsh K, Isner JM, Asahara T. (2001). HVIG-CoA reductase inhibitor mobilizes bone marrow-derived endothelial progenitor cells. J Clin Invest 108:399–405.
   PubMed Web of Science ®Google Scholar
• Moncada S, Palmer RM, Higgs EA. (1991). Nitric oxide: physiology, pathophysiology, and pharmacol-ogy. Pharmacol Rev 43:109–142.
   PubMed Web of Science ®Google Scholar
• Moncada S, Palmer RMJ, Higgs EA. (1990). Nitric oxide: the endogenous regulator of vascular tone. In: The Endothelium: An Introduction to Current Re-search. (Warren GB, Ed.). Wiley-Liss, New York-Toronto-Singapore: p. 1–6.
   Google Scholar
• Moulton KS. (2001). Plaque angiogenesis and ath-erosclerosis. Curr Atheroscler Rep 3:225–233.
   PubMedGoogle Scholar
• Mueck AO, Seeger H, Wallwiener D. (2001). Fur-ther evidence for direct vascular actions of statins: effect on endothelial nitric oxide synthase and ad-hesion molecules. Exp Clin Endocrinol Diabetes 109:181–183.
   PubMed Web of Science ®Google Scholar
• Murohara T, Parkinson SJ, Waldman SA, Lefer AM. (1995). Inhibition of nitric oxide biosynthesis pro-motes P-selectin expression in platelets. Role of pro-tein kinase C. Arterioscler Thromb Vasc Biol 15: 2068–2075.
   PubMed Web of Science ®Google Scholar
• Ohara Y, Peterson TE, Harrison DG. (1993). Hy-percholesterolemia increases endothelial superoxide anion production. J Clin Invest 91:2546–2551.
   PubMed Web of Science ®Google Scholar
• Ohno M, Gibbons GH, Dzau VJ, Cooke JP. (1993). Shear stress elevates endothelial cGMP. Role of a potassium channel and G protein coupling. Circula-tion 88:193–197.
   Google Scholar
• Provost P, Lam JY, Lacoste L, Merhi Y, Waters D. (1994). Endothelium-derived nitric oxide attenu-ates neutrophil adhesion to endothelium under ar-terial flow conditions. Arterioscler Thromb 14:331–335.
   Google Scholar
• Pruefer D, Scalia R, Lefer AM. (1999). Sirnvastatin inhibits leukocyte-endothelial cell interactions and protects against inflammatory processes in normo-cholesterolemic rats. Arterioscler Thromb Vasc Biol 19:2894–2900.
   PubMed Web of Science ®Google Scholar
• Radomski MW, Palmer RM, Moncada S. (1987). Endogenous nitric oxide inhibits human platelet ad-hesion to vascular endothelium. Lancet 2:1057–1058.
   PubMed Web of Science ®Google Scholar
• Regrigny O, Atkinson J, Capdeville-Atkinson C, Lirninana P, Chillon JM. (2000). Effect of lovastatin on cerebral circulation in spontaneously hyperten-sive rats. Hypertension 35:1105–1110.
   Google Scholar
• Reuther GW, Der CJ. (2000). The Ras branch of small GTPases: Ras family members don't fall far from the tree. Curr Opin Cell Biol 12:157–165.
   PubMed Web of Science ®Google Scholar
• Rubanyi GM, Vanhoutte PM. (1986). Superoxide anions and hyperoxia inactivate endothelium- derived relaxing factor. Am J Physiol 250:H822–H827.
   PubMed Web of Science ®Google Scholar
• Salas A, Panes J, Rosenbloom CL, Elizalde JI, Anderson DC, Granger DN, Pique JM. (1999). Dif-ferential effects of a nitric oxide donor on reperfu-sion-induced microvascular dysfunction in diabetic and non-diabetic rats. Diabetologia 42:1350–1358.
   Google Scholar
• Scalia R, Gefen J, Petasis NA, Serhan CN, Lefer AM. (1997). Lipoxin A4 stable analogs inhibit leukocyte rolling and adherence in the rat mesenteric micro-vasculature: role of P-selectin. Proc Natl Acad Sci USA 94:9967–9972.
   PubMed Web of Science ®Google Scholar
• Scalia R, Gooszen ME, Jones SP, Hoffmeyer M, Rim-mer DM III, Trocha SD, Huang PL, Smith MB, Lefer AM, Lefer DJ. (2001). Simvastatin exerts both anti-inflammatory and cardioprotective effects in apoli-poprotein E -deficient mice. Circulation 103:2598–2603.
   PubMed Web of Science ®Google Scholar
• Schwartz MA, Shattil SJ. (2000). Signaling net-works linking integrins and rho family GTPases. Trends Biochem Sci 25:388–391.
   PubMed Web of Science ®Google Scholar
• Stalker TJ, Lefer AM, Scalia R. (2001). A new HVIG-CoA reductase inhibitor, rosuvastatin, exerts anti-inflammatory effects on the microvascular en-dothelium: the role of mevalonic acid. Br J Pharma-col 133:406–412.
   PubMed Web of Science ®Google Scholar
• Stepp DW, Nishikawa Y, Chaim WM. (1999). Regulation of shear stress in the canine coronary micro circulation. Circulation 100:1555–1561.
   Google Scholar
• Sterzer P, Meintzschel F, Rosler A, Lanfermann H, Steinmetz H, Sitzer M. (2001). Pravastatin im-proves cerebral vasomotor reactivity in patients with subcortical small-vessel disease. Stroke 32:2817–2820.
   PubMed Web of Science ®Google Scholar
• Takemoto M, Sun J, Hiroki J, Shirnokawa H, Liao JK. (2002). Rho-kinase mediates hypoxia-induced downregulation of endothelial nitric oxide synthase. Circulation 106:57–62.
   PubMed Web of Science ®Google Scholar
• Thurston G, Baluk P, McDonald DM. (2000). De-terminants of endothelial cell phenotype in venules. Microcirculation 7:67–80.
   Google Scholar
• Tsao PS, Buitrago R, Chan JR, Cooke JP. (1996). Fluid flow inhibits endothelial adhesiveness. Nitric oxide and transcriptional regulation of VCA1VI-1. Circulation 94:1682–1689.
   PubMed Web of Science ®Google Scholar
• Tsao PS, Lewis NP, Alpert S, Cooke JP. (1995). Exposure to shear stress alters endothelial adhesive-ness. Role of nitric oxide. Circulation 92:3513–3519.
   Google Scholar
• Vallance P, Collier J, Moncada S. (1989). Effects of endothelium-derived nitric oxide on peripheral ar-teriolar tone in man. Lancet 2:997–1000.
   PubMed Web of Science ®Google Scholar
• Van Aelst L, D'Souza-Schorey C. (1997). Rho GT-Pases and signaling networks. Genes Dev 11:2295–2322.
   PubMed Web of Science ®Google Scholar
• van Nieuw Arnerongen GP, Vermeer MA, Negre-Aminou P, Lankelma J, Emeis JJ, van Hinsbergh VW. (2000). Sirnvastatin improves disturbed endo- thelial barrier function. Circulation 102 : 2803–2809.
   Google Scholar
• Vasa M, Fichtlscherer S, Adler K, Aicher A, Martin H, Zeiher AM, Dirnrneler S. (2001). Increase in cir-culating endothelial progenitor cells by statin therapy in patients with stable coronary artery dis-ease. Circulation 103:2885–2890.
   PubMed Web of Science ®Google Scholar
• Vasquez-Vivar J, Kalyanararnan B, Martasek P, Hogg N, Masters BS, Karoui H, Tordo P, Pritchard KA Jr. (1998). Superoxide generation by endothelial nitric oxide synthase: the influence of cofactors. Proc Natl Acad Sci USA 95:9220–9225.
   PubMed Web of Science ®Google Scholar
• Vaughan CJ, Delanty N. (1999). Neuroprotective properties of statins in cerebral ischemia and stroke. Stroke 30:1969–1973.
   PubMed Web of Science ®Google Scholar
• Vaughan CJ, Delanty N, Basson CT. (2001). Do st-atins afford neuroprotection in patients with cere-bral ischaemia and stroke? CNS Drugs 15:589–596.
   Google Scholar
• Vincent L, Chen W, Hong L, Mirshahi F, Mishal Z, Mirshahi-Khorassani T, Vannier JP, Soria J, Soria C. (2001). Inhibition of endothelial cell migration by cerivastatin, an HVIG-CoA reductase inhibitor: contribution to its anti-angiogenic effect. FERS Lett 495:159–166.
   Google Scholar
• Wagner AH, Kohler T, Ruckschloss U, Just I, Hecker M. (2000). Improvement of nitric oxide-dependent vasodilatation by HVIG-CoA reductase inhibitors through attenuation of endothelial superoxide anion formation. Arterioscler Thromb Vasc Biol 20:61–69.
   PubMed Web of Science ®Google Scholar
• Walter DH, Rittig K, Bahlrnann FH, Kirchmair R, Silver M, Murayarna T, Nishimura H, Losordo DW, Asahara T, Isner JM. (2002). Statin therapy accel-erates reendothelialization: a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells. Circulation 105:3017–3024.
   PubMed Web of Science ®Google Scholar
• Wassmann S, Laufs U, Baurner AT, Muller K, Ahl-bory K, Linz W, Itter G, Rosen R, Bohm M, Nickenig G. (2001). HVIG-CoA reductase inhibitors improve endothelial dysfunction in normocholesterolemic hypertension via reduced production of reactive oxygen species. Hypertension 37:1450–1457.
   PubMed Web of Science ®Google Scholar
• Weber C, Erl W, Weber KS, Weber PC. (1997). HVIG-CoA reductase inhibitors decrease CD11b ex-pression and CD11b-dependent adhesion of mono-cytes to endothelium and reduce increased adhesive-ness of monocytes isolated from patients with hy-p ercholesterolemia. J Am Coll Cardiol 30 : 1212–1217.
   PubMed Web of Science ®Google Scholar
• Weis M, Heeschen C, Glassford AJ, Cooke JP. (2002). Statins have biphasic effects on angiogene-sis. Circulation 105:739–745.
   PubMed Web of Science ®Google Scholar
• Weis M, Pehlivanli S, Meiser BM, von Scheidt W. (2001). Sirnvastatin treatment is associated with improvement in coronary endothelial function and decreased cytokine activation in patients after heart transplantation. J Am Coll Cardiol 38:814–818.
   PubMed Web of Science ®Google Scholar
• Weitz-Schmidt G, Welzenbach K, Brinkmann V, Karnata T, Kallen J, Bruns C, Cottens S, Takada Y, Hommel U. (2001). Statins selectively inhibit leu-kocyte function antigen-1 by binding to a novel regulatory integrin site. Nat Med 7:687–692.
   PubMed Web of Science ®Google Scholar
• Williams JK, Armstrong ML, Heistad DD. (1988). Vasa vasorurn in atherosclerotic coronary arteries: responses to vasoactive stimuli and regression of atherosclerosis. Circ Res 62:515–523.
   Google Scholar
• Wilson SH, Herrmann J, Lerman LO, Holmes DR Jr, Napoli C, Ritrnan EL, Lerman A. (2002). Sirnvas-tatin preserves the structure of coronary adventitial vasa vasorurn in experimental hypercholesterolemia independent of lipid lowering. Circulation 105:415–418.
   PubMed Web of Science ®Google Scholar
• Yao SK, Akhtar S, Scott-Burden T, Ober JC, Golino P, Buja LM, Casscells W, Willerson JT. (1995). En- dogenous and exogenous nitric oxide protect against intracoronary thrombosis and reocclusion after thrombolysis . Circulation 92:1005–1010.
   PubMed Web of Science ®Google Scholar
• Yoshida M, Sawada T, Ishii H, Gerszten RE, Rosen-zweig A, Girnbrone MA Jr, Yasukochi Y, Nurnano F. (2001). Hrng-CoA reductase inhibitor modulates monocyte-endothelial cell interaction under physi-ological flow conditions in vitro: involvement of Rho GTPase- dependent mechanism. Arterioscler Thromb Vasc Biol 21:1165–1171.
   PubMedGoogle Scholar
• Zweifach BW, Lipowsky III I. (1984). Pressure-flowregulation in blood and lymph microcirculation. In: Handbook of Physiology. The Cardiovascular Sys-tem: Microcirculation. (Renkin EM, Michel CC, Eds.). American Physiological Society, Bethesda, MD: p. 251-307.
   Google Scholar