Propionyl-l-carnitine improves postischemic blood flow recovery and arteriogenetic revascularization and reduces endothelial NADPH-oxidase 4-mediated superoxide production

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 30, Issue 3, 2010, Pages 426-435

  Stasi, Maria Antonietta ^a   Scioli, Maria Giovanna ^b   Arcuri, Gaetano ^b   Mattera, Giovan Giuseppe ^a   Lombardo, Katia ^a   Marcellini, Marcella ^a   Riccioni, Teresa ^a   De Falco, Sandro ^c   Pisano, Claudio ^a   Spagnoli, Luigi Giusto ^b   Borsini, Franco ^a   Orlandi, Augusto ^b  

^a General Pharmacology and Oncology Department   (Italy)

^b UNIVERSITY OF ROME TOR VERGATA   (Italy)

^c INSTITUTE OF GENETICS AND BIOPHYSICS ADRIANO BUZZATI TRAVERSO   (Italy)

Author keywords

Arteriogenesis; Endothelial function; Oxidative stress; Vascular function

Indexed keywords

IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERCELLULAR ADHESION MOLECULE 1; PROPIONYLCARNITINE; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 2; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 4; SUPEROXIDE; VASCULOTROPIN;

ANGIOGENESIS; ANIMAL CELL; ANTIOXIDANT ACTIVITY; ARTERY ENDOTHELIUM; ARTICLE; BLOOD VESSEL DIAMETER; CAPILLARY; CELL PROLIFERATION; CHORIOALLANTOIS; CONTROLLED STUDY; DOPPLER FLOWMETRY; ENDOTHELIAL DYSFUNCTION; ENDOTHELIUM CELL; FEMORAL ARTERY FLOW; GROWTH REGULATION; HISTOPATHOLOGY; HUMAN; HUMAN CELL; LIMB BLOOD FLOW; LIMB ISCHEMIA; MALE; MOUSE; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN INDUCTION; TRANSCRIPTION REGULATION; UMBILICAL VEIN; VASODILATATION;

ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; BLOOD VESSELS; CARNITINE; CELL PROLIFERATION; CHICK EMBRYO; CHORIOALLANTOIC MEMBRANE; COLLATERAL CIRCULATION; DISEASE MODELS, ANIMAL; ENDOTHELIUM, VASCULAR; HINDLIMB; HUMANS; INTERCELLULAR ADHESION MOLECULE-1; ISCHEMIA; MICE; NADPH OXIDASE; NEOVASCULARIZATION, PHYSIOLOGIC; RABBITS; REGIONAL BLOOD FLOW; SUPEROXIDES; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 77649148275     PISSN: 10795642     EISSN: None     Source Type: Journal    
DOI: 10.1161/ATVBAHA.109.201533     Document Type: Article

References (47)

1. Hiatt WR. Medical treatment of peripheral arterial disease and claudi-cation. N Engl J Med. 2001;344:1608-1621.
2. Hankey GJ, Norman PE, Eikelboom JW. Medical treatment of peripheral arterial disease. JAMA. 2006;295:547-553.
3. Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res. 2000;87:840-844.
4. Brevetti G, Schiano V, Chiariello M. Endothelial dysfunction: a key to the pathophysiology and natural history of peripheral arterial disease? Atherosclerosis. 2008;197:1-11.
5. Bremer J. Carnitine\metabolism and functions. Physiol Rev. 1983;63: 1420-1480.
6. Bieber LL. Carnitine Annu Rev Biochem. 1988;57:261-283.
7. Brevetti G, Diehm C, Lambert D. European multicenter study on propionyl-L-carnitine in intermittent claudication. J Am Coll Cardiol. 1999;34:1618-1624.
8. Davis EJ, Spydevold O, Bremer J. Pyruvate carboxylase and propionyl-CoA carboxylase as anaplerotic enzymes in skeletal muscle mitochondria. Eur J Biochem. 1980;110:255-262.
9. Orlandi A, Marcellini M, Pesce D, Calvani M, Spagnoli LG. Propionyl-L-carnitine reduces intimal hyperplasia after injury in normocholesterol-emic rabbit carotid artery by modulating proliferation and caspase 3-dependent apoptosis of vascular smooth muscle cells. Atherosclerosis. 2002;160:81-89.
10. Loffredo L, Marcoccia A, Pignatelli P, Andreozzi P, Borgia MC, Cangemi R, Chiarotti F, Violi F. Oxidative-stress-mediated arterial dysfunction in patients with peripheral arterial disease. Eur Heart J. 2007; 28:608-612.
11. Risau W. Mechanisms of angiogenesis. Nature. 1997;386:671-674.
12. Scholz D, Ito W, Fleming I, Deindl E, Sauer A, Wiesnet M, Busse R, Schaper J, Schaper W. Ultrastructure and molecular histology of rabbit hind-limb collateral artery growth (arteriogenesis). Virchows Arch. 2000; 436:257-270.
13. Heil M, Schaper W. Influence of mechanical, cellular, and molecular factors on collateral artery growth (arteriogenesis). Circ Res. 2004;95: 449-458.
14. Pu LQ, Sniderman AD, Arekat Z, Graham AM, Brassard R, Symes JF. Angiogenic growth factor and revascularization of the ischemic limb: evaluation in a rabbit model. J Surg Res. 1993;54:575-583.
15. Rissanen TT, Markkanen JE, Arve K, Rutanen J, Kettunen MI, Vajanto I, Jauhiainen S, Cashion L, Gruchala M, Narvanen O, Taipale P, Kauppinen RA, Rubanyi GM, Yla-Herttuala S. Fibroblast growth factor 4 induces vascular permeability, angiogenesis and arteriogenesis in a rabbit hindlimb ischemia model. Faseb J. 2003;17:100-102.
16. Orlandi A, Ferlosio A, Ciucci A, Sesti F, Lifschitz-Mercer B, Gabbiani G, Spagnoli LG, Czernobilsky B. Cellular retinol-binding protein-1 expression in endometrial stromal cells: physiopathological and diagnostic implications. Histopathology. 2004;45:511-517.
17. Orlandi A, Francesconi A, Marcellini M, Di Lascio A, Spagnoli LG. Propionyl-L-carnitine reduces proliferation and potentiates Bax-related apoptosis of aortic intimal smooth muscle cells by modulating nuclear factor-kappaB activity. J Biol Chem. 2007;282:4932-4942.
18. Ago T, Kitazono T, Ooboshi H, Iyama T, Han YH, Takada J, Wakisaka M, Ibayashi S, Utsumi H, Iida M. Nox4 as the major catalytic component of an endothelial NAD(P)H oxidase. Circulation. 2004;109:227-233
19. Carmeliet P. vascular endothelial growth factor gene therapy: stimulating angiogenesis or angioma-genesis? Nat Med. 2000;6:1102-1103.
20. Van Weel V, van Tongeren RB, van Hinsbergh VW, van Bockel JH, Quax PH. Vascular growth in ischemic limbs: a review of mechanisms and possible therapeutic stimulation. Ann Vasc Surg. 2008;22:582-597.
21. Davies PF. Flow-mediated endothelial mechanotransduction. Physiol Rev. 1995;75:519-560.
22. Schaper W, Scholz D. Factors regulating arteriogenesis. Arterioscler Thromb Vasc Biol. 2003;23:1143-1151.
23. Eitenmuller I, Volger O, Kluge A, Troidl K, Barancik M, Cai WJ, Heil M, Pipp F, Fischer S, Horrevoets AJ, Schmitz-Rixen T, Schaper W. The range of adaptation by collateral vessels after femoral artery occlusion. Circ Res. 2006;99:656-662.
24. Cipolla MJ, Nicoloff A, Rebello T, Amato A, Porter JM. Propionyl-L-carnitine dilates human subcutaneous arteries through an endothelium-dependent mechanism. J Vasc Surg. 1999;29:1097-1103.
25. 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;82:1094-1101.
26. Violi F, Loffredo L, Marcoccia A. Antioxidants in peripheral arterial disease. Curr Drug Targets Cardiovasc Haematol Disord. 2004;4: 289-294.
27. Gunnett CA, Lund DD, McDowell AK, Faraci FM, Heistad DD. Mechanisms of inducible nitric oxide synthase-mediated vascular dysfunction. Arterioscler Thromb Vasc Biol. 2005;25:1617-1622.
28. McDermott MM, Ferrucci L, Guralnik JM, Tian L, Green D, Liu K, Tan J, Liao Y, Pearce WH, Schneider JR, Ridker P, Rifai N, Hoff F, Criqui MH. Elevated levels of inflammation, d-dimer, and homocysteine are associated with adverse calf muscle characteristics and reduced calf strength in peripheral arterial disease. J Am Coll Cardiol. 2007;50: 897-905.
29. Hoefer IE, van Royen N, Rectenwald JE, Deindl E, Hua J, Jost M, Grundmann S, Voskuil M, Ozaki CK, Piek JJ, Buschmann IR. Arterio-genesis proceeds via ICAM-1/Mac-1-mediated mechanisms. Circ Res. 2004;94:1179-1185.
30. Schirmer SH, Buschmann IR, Jost MM, Hoefer IE, Grundmann S, Andert JP, Ulusans S, Bode C, Piek JJ, van Royen N. Differential effects of MCP-1 and leptin on collateral flow and arteriogenesis. Cardiovasc Res. 2004;64:356-364.
31. Galley HF, Webster NR. Physiology of the endothelium. Br J Anaesth. 2004;93:105-113.
32. Shears LL, Kawaharada N, Tzeng E, Billiar TR, Watkins SC, Kovesdi I, Lizonova A, Pham SM. Inducible nitric oxide synthase suppresses the development of allograft arteriosclerosis. J Clin Invest. 1997;100: 2035-2042. (Pubitemid 27459358)
33. Paulson DJ, Traxler J, Schmidt M, Noonan J, Shug AL. Protection of the ischaemic myocardium by L-propionylcarnitine: effects on the recovery of cardiac output after ischaemia and reperfusion, carnitine transport, and fatty acid oxidation. Cardiovasc Res. 1986;20:536-541.
34. Weber C, Erl W, Pietsch A, Strobel M, Ziegler-Heitbrock HW, Weber PC. Antioxidants inhibit monocyte adhesion by suppressing nuclear factor-kappa B mobilization and induction of vascular cell adhesion molecule-1 in endothelial cells stimulated to generate radicals. Arte-rioscler Thromb. 1994;14:1665-1673.
35. Jung Y, Song S, Choi C. Peroxisome proliferator activated receptor gamma agonists suppress TNFalpha-induced ICAM-1 expression by en-dothelial cells in a manner potentially dependent on inhibition of reactive oxygen species. Immunol Lett. 2008;117:63-69.
36. Tummala PE, Chen XL, Medford RM. NF-kappa B independent suppression of endothelial vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 gene expression by inhibition of flavin binding proteins and superoxide production. J Mol Cell Cardiol. 2000; 32:1499-1508.
37. Epstein SE, Stabile E, Kinnaird T, Lee CW, Clavijo L, Burnett MS. Janus phenomenon: the interrelated tradeoffs inherent in therapies designed to enhance collateral formation and those designed to inhibit atherogenesis. Circulation. 2004;109:2826-2831.
38. Hiatt WR, Regensteiner JG, Creager MA, Hirsch AT, Cooke JP, Olin JW, Gorbunov GN, Isner J, Lukjanov YV, Tsitsiashvili MS, Zabelskaya TF, Amato A. Propionyl-L-carnitine improves exercise performance and functional status in patients with claudication. Am J Med. 2001;110: 616-622.
39. Pola P, Flore R, Tondi P, Nolfe G. Rheological activity of propionyl L-carnitine. Drugs Exp Clin Res. 1991;17:191-196.
40. Corsico N, Nardone A, Lucreziotti MR, Spagnoli LG, Pesce D, Aureli T, Di Cocco ME, Miccheli A, Conti F, Arrigoni Martelli E. Effect of propionyl-L-carnitine in a rat model of peripheral arteriopathy: a functional, histologic, and NMR spectroscopic study. Cardiovasc Drugs Ther. 1993;7:241-251.
41. van der Wal AC, Das PK, Tigges AJ, Becker AE. Adhesion molecules on the endothelium and mononuclear cells in human atherosclerotic lesions. Am J Pathol. 1992;141:1427-1433.
42. Brevetti G, Piscione F, Cirillo P, Galasso G, Schiano V, Barbato E, Scopacasa F, Chiariello M. In concomitant coronary and peripheral arterial disease, inflammation of the affected limbs predicts coronary artery endothelial dysfunction. Atherosclerosis. 2008;201:440-446.
43. Chen CH, Jiang W, Via DP, Luo S, Li TR, Lee YT, Henry PD. Oxidized low-density lipoproteins inhibit endothelial cell proliferation by suppressing basic fibroblast growth factor expression. Circulation. 2000;101: 171-177.
44. Tirziu D, Moodie KL, Zhuang ZW, Singer K, Helisch A, Dunn JF, Li W, Singh J, Simons M. Delayed arteriogenesis in hypercholesterolemic mice. Circulation. 2005;112:2501-2509.
45. Davenport RJ, Law MP, Pike VW, Osman S, Poole KG. Propionyl-L-carnitine: labelling in the N-methyl position with carbon-11 and pharma-cokinetic studies in rats. Nucl Med Biol. 1995;22:699-709.
46. Spagnoli LG, Orlandi A, Marino B, Mauriello A, De Angelis C, Ramacci MT. Propionyl-L-carnitine prevents the progression of atherosclerotic lesions in aged hyperlipemic rabbits. Atherosclerosis. 1995;114:29-44.
47. Ito WD, Arras M, Scholz D, Winkler B, Htun P, Schaper W. Angio-genesis but not collateral growth is associated with ischemia after femoral artery occlusion. Am J Physiol. 1997;273:H1255-H1265.