Potential benefit of statins for vascular disease in systemic sclerosis

Current Opinion in Rheumatology

Volumn 18, Issue 6, 2006, Pages 594-600

  Kuwana, Masataka ^a  

^a KEIO UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

Endothelial cells; Pleiotropic effect; Vasculogenesis

Indexed keywords

ATORVASTATIN; CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LIPID; SIMVASTATIN;

ANGIOGENESIS; CELL DIFFERENTIATION; CELL MOTILITY; CHOLESTEROL SYNTHESIS; CLINICAL TRIAL; DRUG ACTIVITY; DRUG EFFECT; DRUG MECHANISM; ENDOTHELIAL DYSFUNCTION; ENDOTHELIUM CELL; ENDOTHELIUM INJURY; FIBROSIS; HUMAN; INFLAMMATION; INHIBITION KINETICS; LIPOGENESIS; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTECTION; REVIEW; SYSTEMIC SCLEROSIS; VASCULAR DISEASE; VASCULAR ENDOTHELIUM;

BLOOD VESSELS; ENDOTHELIUM, VASCULAR; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; MEVALONIC ACID; NEOVASCULARIZATION, PATHOLOGIC; SCLERODERMA, SYSTEMIC;

EID: 33750221321     PISSN: 10408711     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.bor.0000245720.02512.3e     Document Type: Review

References (77)

1. LeRoy EC. Systemic sclerosis: a vascular perspective. Rheum Dis Clin North Am 1996; 22:675-694.
2. Kuwana M, Okazaki Y, Yasuoka H, et al. Defective vasculogenesis in systemic sclerosis. Lancet 2004; 364:603-610.
3. Schachna L, Wigley FM. Targeting mediators of vascular injury in scleroderma. Curr Opin Rheumatol 2002; 14:686-693.
4. Maron DJ, Fazio S, Linton MF. Current perspectives on statins. Circulation 2000; 101:207-213.
5. Takemoto M, Liao JK. Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Arterioscler Thromb Vasc Biol 2001; 21:1712-1719.
6. Herrick AL. Pathogenesis of Raynaud's phenomenon. Rheumatology 2005; 44:587-596.
7. Konttinen YT, Mackiewicz Z, Ruuttila P, et al. Vascular damage and lack of angiogenesis in systemic sclerosis skin. Clin Rheumatol 2003; 22:196-202.
8. Mackiewicz Z, Sukura A, Povilenaite D, et al. Increased but imbalanced expression of VEGF and its receptors has no positive effect on angiogenesis in systemic sclerosis skin. Clin Exp Rheumatol 2002; 20:641-646.
9. Distler O, Distler JH, Scheid A, et al. Uncontrolled expression of vascular endothelial growth factor and its receptors leads to insufficient skin angiogenesis in patients with systemic sclerosis. Circ Res 2004; 95:109-116.
10. Ann Davies C, Jeziorska M, Freemont AJ, Herrick AL. The differential expression of VEGF, VEGFR-2, and GLUT-1 proteins in disease subtypes of systemic sclerosis. Hum Pathol 2006; 37:190-197.
11. Distler O, Del Rosso A, Giacomelli R, et al. Angiogenic and angiostatic factors in systemic sclerosis: increased levels of vascular endothelial growth factor are a feature of the earliest disease stages and are associated with the absence of fingertip ulcers. Arthritis Res 2002; 4:R11.
12. Giusti B, Serrati S, Margheri F, et al. The antiangiogenic tissue kallikrein pattern of endothelial cells in systemic sclerosis. Arthritis Rheum 2005; 52:3618-3628. This microarray-based gene profiling study of normal and SSc microvascular endothelial cells found critical alterations in the angiogenesis-modulating tissue kallikreins.
13. Stummvoll GH, Aringer M, Grisar J, et al. Increased transendothelial migration of scleroderma lymphocytes. Ann Rheum Dis 2004; 63:569-574.
14. Worda M, Sgonc R, Dietrich H, et al. In vivo analysis of the apoptosis-inducing effect of antiendothelial cell antibodies in systemic sclerosis by the chorionallantoic membrane assay. Arthritis Rheum 2003; 48:2605-2614.
15. Satoh T, Kimura K, Okano Y, et al. Lack of circulating autoantibodies to bone morphogenetic protein receptor-II or activin receptor-like kinase 1 in mixed connective tissue disease patients with pulmonary arterial hypertension. Rheumatology 2005; 44:192-196.
16. Caplice NM, Doyle B. Vascular progenitor cells: origin and mechanisms of mobilization, differentiation, integration, and vasculogenesis. Stem Cells Dev 2005; 14:122-139.
17. Caprioli A, Jaffredo T, Gautier R, et al. Blood-borne seeding by hematopoietic and endothelial precursors from the allantois. Proc Natl Acad Sci U S A 1998; 95:1641-1646.
18. + cells identifies a population of functional endothelial precursors. Blood 2000; 95:952-958.
19. Asahara T, Masuda H, Takahashi T, et al. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 1999; 85:221-228.
20. + bone marrow cells. Blood 2000; 95:581-585.
21. + endothelial precursor cells. Circ Res 2001; 88:167-174.
22. Murayama T, Tepper OM, Silver M, et al. Determination of bone marrow-derived endothelial progenitor cell significance in angiogenic growth factor-induced neovascularization in vivo. Exp Hematol 2002; 30:967-972.
23. Takahashi T, Kalka C, Masuda H, et al. Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 1999; 5:434-438.
24. Vasa M, Fichtlscherer S, Aicher A, et al. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 2001; 89:e1-e7.
25. Takai Y, Sasaki T, Matozaki T. Small GTP-binding proteins. Physiol Rev 2001; 81:153-208.
26. Cohen LH, Pieterman E, van Leeuwen REW, et al. Inhibitors of prenylation of Ras and other G-proteins and their application as therapeutics. Biochem Pharmacol 2000; 60:1061-1068.
27. Etienne-Manneville S, Hall A. Rho GTPases in cell biology. Nature 2002; 420:629-635.
28. Sata M, Walsh K. Oxidized LDL activates Fas-mediated endothelial cell apoptosis. J Clin Invest 1998; 102:1682-1689.
29. Vindis C, Elbaz M, Escargueil-Blanc I, et al. Two distinct calcium-dependent mitochondrial pathways are involved in oxidized LDL-induced apoptosis. Arterioscler Thromb Vasc Biol 2005; 25:639-645.
30. Inoue M, Itoh H, Tanaka T, et al. Oxidized LDL regulates vascular endothelial growth factor expression in human macrophages and endothelial cells through activation of peroxisome proliferators-activated receptor-g. Arterioscler Thromb Vasc Biol 2001; 21:560-566.
31. Romero LI, Zhang DN, Cooke JP, et al. Differential expression of nitric oxide by dermal microvascular endothelial cells from patients with scleroderma. Vasc Med 2000; 5:147-158.
32. Andersen GN, Caidahl K, Kazzam E, et al. Correlation between increased nitric oxide production and markers of endothelial activation in systemic sclerosis: findings with the soluble adhesion molecules E-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1. Arthritis Rheum 2000; 43:1085-1093.
33. Fatini C, Gensini F, Sticchi E, et al. High prevalence of polymorphisms of angiotensin-converting enzyme (I/D) and endothelial nitric oxide synthase (Glu298Asp) in patients with systemic sclerosis. Am J Med 2002; 112:540-544.
34. Assassi S, Mayes MD, McNearney T, et al. Polymorphisms of endothelial nitric oxide synthase and angiotensin-converting enzyme in systemic sclerosis. Am J Med 2005; 118:907-911.
35. Laufs U, La Fata V, Plutzky J, Liao JK. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation 1998; 97:1129-1135.
36. Laufs U, Endres M, Stagliano N, et al. Neuroprotection mediated by changes in the endothelial actin cytoskeleton. J Clin Invest 2000; 106:15-24.
37. Kalinowski L, Dobrucki IT, Malinski T. Cerivastatin potentiates nitric oxide release and eNOS expression through inhibition of isoprenoids synthesis. J Physiol Pharmacol 2002; 53:585-595.
38. Fulton D, Gratton JP, McCabe TJ, et al. Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature 1999; 399:597-601.
39. Dimmeler S, Fleming I, Fisslthaler B, et al. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature 1999; 399:601-605.
40. Shishehbor MH, Brennan ML, Aviles RJ, et al. Statins promote potent systemic antioxidant effects through specific inflammatory pathways. Circulation 2003; 108:426-431.
41. Rueckschloss U, Galle J, Holtz J, et al. 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; 104:1767-1772.
42. Kureishi Y, Luo Z, Shiojima I, et al. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med 2000; 6:1004-1010.
43. Dimmeler S, Aicher A, Vasa M, et al. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. J Clin Invest 2001; 108:391-397.
44. Llevadot J, Murasawa S, Kureishi Y, et al. HMG-CoA reductase inhibitor mobilizes bone marrow-derived endothelial progenitor cells. J Clin Invest 2001; 108:399-405.
45. Walter DH, Rittig K, Bahlmann FH, et al. Statin therapy accelerates reendothelialization: a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells. Circulation 2002; 105:3017-3024.
46. Werner N, Priller J, Laufs U, et al. Bone marrow-derived progenitor cells modulate vascular reendothelialization and neointimal formation: effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition. Arterioscler Thromb Vasc Biol 2002; 22:1567-1572.
47. Vasa M, Fichtlscherer S, Adler K, et al. Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease. Circulation 2001; 103:2885-2890.
48. Aicher A, Heeschen C, Mildner-Rihm C, et al. Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells. Nat Med 2003; 9:1370-1376.
49. Assmus B, Urbich C, Aicher A, et al. HMG-CoA reductase inhibitors reduce senescence and increase proliferation of endothelial progenitor cells via regulation of cell cycle regulatory genes. Circ Res 2003; 92:1049-1055.
50. Urbich C, Dernbach E, Zeiher AM, Dimmeler S. Double-edged role of statins in angiogenesis signaling. Circ Res 2002; 90:737-744.
51. Weis M, Heeschen C, Glassford AJ, Cooke JP. Statins have biphasic effects on angiogenesis. Circulation 2002; 105:739-745.
52. Vollmer T, Key L, Durkalski V, et al. Oral simvastatin treatment in relapsing-remitting multiple sclerosis. Lancet 2004; 363:1607-1608.
53. McCarey DW, McInnes IB, Madhok R, et al. Trial of atorvastatin in rheumatoid arthritis (ATRA): double-blinded, randomised placebo-controlled trial. Lancet 2004; 363:2015-2021.
54. Abeles AM, Pillinger MH. Statins as anti-inflammatory and immunomodulatory agents: A future in rheumatologic therapy. Arthritis Rheum 2006; 54:393-407.
55. Obama R, Ishida H, Takizawa S, et al. Direct inhibition by a statin of TNFα-induced leukocyte recruitment in rat pial venules - in vivo confocal microscopic study. Pathophysiology 2004; 11:121-128.
56. Fischetti F, Carretta R, Borotto G, et al. Fluvastatin treatment inhibits leucocyte adhesion and extravasation in models of complement-mediated acute inflammation. Clin Exp Immunol 2004; 135:186-193.
57. Weitz-Schmidt G, Welzenbach K, Brinkmann V, et al. Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat Med 2001; 7:687-692.
58. Steffens S, Mach F. Anti-inflammatory properties of statins. Semin Vasc Med 2004; 4:417-422.
59. Hasegawa M, Sato S, Takehara K. Augmented production of chemokines (monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1α) and MIP-1β) in patients with systemic sclerosis: MCP-1 and MIP-1alpha may be involved in the development of pulmonary fibrosis. Clin Exp Immunol 1999; 117:159-165.
60. Carulli MT, Ong VH, Ponticos M, et al. Chemokine receptor CCR2 expression by systemic sclerosis fibroblasts: evidence for autocrine regulation of myo fibroblast differentiation. Arthritis Rheum 2005; 52:3772-3782.
61. Inoue I, Goto S, Mizotani K, et al. Lipophilic HMG-CoA reductase inhibitor has an anti-inflammatory effect: reduction of mRNA levels for interleukin-1β, interleukin-6, cyclooxygenase-2, and p22phox by regulation of peroxisome proliferator-activated receptor alpha (PPARα) in primary endothelial cells. Life Sci 2000; 67:863-876.
62. Dichtl W, Dulak J, Frick M, et al. HMG-CoA reductase inhibitors regulate inflammatory transcription factors in human endothelial and vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 2003; 23:58-63.
63. Cammarano MS, Minden A. Dbl and the Rho GTPases activate NFκB by IκB kinase (IKK)-dependent and IKK-independent pathways. J Biol Chem 2001; 276:25876-25882.
64. Martin G, Duez H, Blanquart C, et al. Statin-induced inhibition of the Rho-signaling pathway activates PPARα and induces HDL apoA-I. J Clin Invest 2001; 107:1423-1432.
65. Zelvyte I, Dominaitiene R, Crisby M, Janciauskiene S. Modulation of inflammatory mediators and PPARγ and NFκB expression by pravastatin in response to lipoproteins in human monocytes in vitro. Pharmacol Res 2002; 45:147-154.
66. Kim SI, Han DC, Lee HB. Lovastatin inhibits transforming growth factor-β1 expression in diabetic rat glomeruli and cultured rat mesangial cells. J Am Soc Nephrol 2000; 11:80-87.
67. Goppelt-Struebe M, Hahn A, Iwanciw D, et al. Regulation of connective tissue growth factor (ccn2; ctgf) gene expression in human mesangial cells: modulation by HMG CoA reductase inhibitors (statins). Mol Pathol 2001; 54:176-179.
68. Heusinger-Ribeiro J, Fischer B, Goppelt-Struebe M. Differential effects of simvastatin on mesangial cells. Kidney Int 2004; 66:187-195.
69. Watts KL, Sampson EM, Schultz GS, Spiteri MA. Simvastatin inhibits growth factor expression and modulates profibrogenic markers in lung fibroblasts. Am J Respir Cell Mol Biol 2005; 32:290-300.
70. Rosenbloom J, Saitta B, Gaidarova S, et al. Inhibition of type I collagen gene expression in normal and systemic sclerosis fibroblasts by a specific inhibitor of geranylgeranyl transferase I. Arthritis Rheum 2000; 43:1624-1632.
71. Louneva N, Huaman G, Fertala J, Jimenez SA. Inhibition of systemic sclerosis dermal fibroblast type I collagen production and gene expression by simvastatin. Arthritis Rheum 2006; 54:1298-1308. This study examined whether statins are capable of modulating collagen gene expression in cultured SSc dermal fibroblasts, and showed that simvastatin is a powerful inhibitor of type I collagen gene expression in normal and systemic sclerosis fibroblasts.
72. Shor R, Halabe A. New trends in the treatment of scleroderma renal crisis. Nephron 2002; 92:716-718.
73. Sule SD, Wigley FM. Treatment of scleroderma: an update. Expert Opin Investig Drugs 2003; 12:471-482.
74. Derk CT, Jimenez SA. Statins and the vasculopathy of systemic sclerosis: potential therapeutic agents? Autoimmun Rev 2006; 5:25-32.
75. Kuwana M, Kaburaki J, Okazaki Y, et al. Increase in circulating endothelial precursors by atorvastatin in patients with systemic sclerosis. Arthritis Rheum 2006; 54:1946-1951. This article describes the first open-label, prospective study evaluating the clinical benefit of statins for improving vascular symptoms in SSc patients. In addition, this study showed that statins can increase CEPs even in SSc patients who have CEP dysfunction.
76. Merkel PA, Herlyn K, Martin RW, et al. Measuring disease activity and functional status in patients with scleroderma and Raynaud's phenomenon. Arthritis Rheum 2002; 46:2410-2420.
77. Cannon CP, Braunwald E, McCabe CH, et al. Comparison of intensive and moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004; 350:1495-1504.