Systemic and vascular oxidation limits the efficacy of oral tetrahydrobiopterin treatment in patients with coronary artery disease

Circulation

Volumn 125, Issue 11, 2012, Pages 1356-1366

  Cunnington, Colin ^a   Van Assche, Tim ^a   Shirodaria, Cheerag ^a   Kylintireas, Ilias ^a   Lindsay, Alistair C ^a   Lee, Justin M ^a   Antoniades, Charalambos ^a   Margaritis, Marios ^a   Lee, Regent ^a   Cerrato, Ruha ^a   Crabtree, Mark J ^a   Francis, Jane M ^a   Sayeed, Rana ^a   Ratnatunga, Chandi ^a   Pillai, Ravi ^a   Choudhury, Robin P ^a   Neubauer, Stefan ^a   Channon, Keith M ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

5,6,7,8, tetrahydrobiopterin; coronary artery disease; endothelium; nitric oxide synthase

Indexed keywords

DIHYDROBIOPTERIN; DITHIOERYTHRITOL; ENDOTHELIAL NITRIC OXIDE SYNTHASE; PLACEBO; SAPROPTERIN; SUPEROXIDE; TETRAHYDROBIOPTERIN;

AGED; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; CORONARY ARTERY BYPASS SURGERY; CORONARY ARTERY DISEASE; DRUG DOSE COMPARISON; DRUG EFFICACY; EX VIVO STUDY; FEMALE; HUMAN; INTERNAL MAMMARY ARTERY; MALE; NUCLEAR MAGNETIC RESONANCE IMAGING; PREOPERATIVE TREATMENT; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SAPHENOUS VEIN; TREATMENT DURATION;

ADMINISTRATION, ORAL; AGED; BIOPTERIN; CORONARY ARTERY DISEASE; DOUBLE-BLIND METHOD; ENDOTHELIUM, VASCULAR; FEMALE; HUMANS; MALE; OXIDATION-REDUCTION; TREATMENT OUTCOME;

EID: 84862794123     PISSN: 00097322     EISSN: 15244539     Source Type: Journal    
DOI: 10.1161/CIRCULATIONAHA.111.038919     Document Type: Article

References (31)

1. Alp NJ, McAteer MA, Khoo J, Choudhury RP, Channon KM. Increased endothelial tetrahydrobiopterin synthesis by targeted transgenic GTPcyclohydrolase I overexpression reduces endothelial dysfunction and atherosclerosis in ApoE-knockout mice. Arterioscler Thromb Vasc Biol. 2004; 24: 445-450. (Pubitemid 38326136)
2. Alp NJ, Mussa S, Khoo J, Guzik TJ, Cai S, Jefferson A, Rockett KA, Channon KM. Tetrahydrobiopterin-dependent preservation of nitric oxide-mediated endothelial function in diabetes by targeted transgenic GTP-cyclohydrolase I overexpression. J Clin Invest. 2003; 112: 725-735. (Pubitemid 38057713)
3. Guzik TJ, Mussa S, Gastaldi D, Sadowski J, Ratnatunga C, Pillai R, Channon KM. Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthase. Circulation. 2002; 105: 1656-1662. (Pubitemid 34298608)
4. Vasquez-Vivar J, Kalyanaraman B, Martasek P, Hogg N, Masters BS, Karoui H, Tordo P, Pritchard KA Jr. Superoxide generation by endothelial nitric oxide synthase: the influence of cofactors. Proc Natl Acad Sci U S A. 1998; 95: 9220-9225. (Pubitemid 28506212)
5. 2/calmodulin-dependent and tetrahydrobiopterin regulatory process. J Biol Chem. 1998; 273: 25804-25808.
6. Antoniades C, Shirodaria C, Crabtree M, Rinze R, Alp N, Cunnington C, Diesch J, Tousoulis D, Stefanadis C, Leeson P, Ratnatunga C, Pillai R, Channon KM. Altered plasma versus vascular biopterins in human atherosclerosis reveal relationships between endothelial nitric oxide synthase coupling, endothelial function, and inflammation. Circulation. 2007; 116: 2851-2859. (Pubitemid 350291226)
7. Antoniades C, Shirodaria C, Van Assche T, Cunnington C, Tegeder I, Lotsch J, Guzik TJ, Leeson P, Diesch J, Tousoulis D, Stefanadis C, Costigan M, Woolf CJ, Alp NJ, Channon KM. GCH1 haplotype determines vascular and plasma biopterin availability in coronary artery disease effects on vascular superoxide production and endothelial function. J Am Coll Cardiol. 2008; 52: 158-165. (Pubitemid 351885444)
8. Maier W, Cosentino F, Lutolf RB, Fleisch M, Seiler C, Hess OM, Meier B, Luscher TF. Tetrahydrobiopterin improves endothelial function in patients with coronary artery disease. J Cardiovasc Pharmacol. 2000; 35: 173-178. (Pubitemid 30073806)
9. Stroes E, Kastelein J, Cosentino F, Erkelens W, Wever R, Koomans H, Luscher T, Rabelink T. Tetrahydrobiopterin restores endothelial function in hypercholesterolemia. J Clin Invest. 1997; 99: 41-46. (Pubitemid 27058292)
10. Heitzer T, Brockhoff C, Mayer B, Warnholtz A, Mollnau H, Henne S, Meinertz T, Munzel T. Tetrahydrobiopterin improves endotheliumdependent vasodilation in chronic smokers: evidence for a dysfunctional nitric oxide synthase. Circ Res. 2000; 86: E36-E41.
11. Heitzer T, Krohn K, Albers S, Meinertz T. Tetrahydrobiopterin improves endothelium-dependent vasodilation by increasing nitric oxide activity in patients with Type II diabetes mellitus. Diabetologia. 2000; 43: 1435-1438.
12. Mayahi L, Heales S, Owen D, Casas JP, Harris J, MacAllister RJ, Hingorani AD. (6R)-5,6,7,8-tetrahydro-L-biopterin and its stereoisomer prevent ischemia reperfusion injury in human forearm. Arterioscler Thromb Vasc Biol. 2007; 27: 1334-1339. (Pubitemid 46809422)
13. Cosentino F, Hurlimann D, Delli Gatti C, Chenevard R, Blau N, Alp NJ, Channon KM, Eto M, Lerch P, Enseleit F, Ruschitzka F, Volpe M, Luscher TF, Noll G. Chronic treatment with tetrahydrobiopterin reverses endothelial dysfunction and oxidative stress in hypercholesterolaemia. Heart. 2008; 94: 487-492. (Pubitemid 351441407)
14. Wiesmann F, Petersen SE, Leeson PM, Francis JM, Robson MD, Wang Q, Choudhury R, Channon KM, Neubauer S. Global impairment of brachial, carotid, and aortic vascular function in young smokers: direct quantification by high-resolution magnetic resonance imaging. J Am Coll Cardiol. 2004; 44: 2056-2064. (Pubitemid 39473292)
15. Skatchkov MP, Sperling D, Hink U, Mulsch A, Harrison DG, Sindermann I, Meinertz T, Munzel T. Validation of lucigenin as a chemiluminescent probe to monitor vascular superoxide as well as basal vascular nitric oxide production. Biochem Biophys Res Commun. 1999; 254: 319-324. (Pubitemid 29290398)
16. Sawabe K, Suetake Y, Nakanishi N, Wakasugi KO, Hasegawa H. Cellular accumulation of tetrahydrobiopterin following its administration is mediated by two different processes; direct uptake and indirect uptake mediated by a methotrexate-sensitive process. Mol Genet Metab. 2005; 86(suppl 1): S133-S138. (Pubitemid 41771122)
17. Crabtree MJ, Smith CL, Lam G, Goligorsky MS, Gross SS. Ratio of 5,6,7,8-tetrahydrobiopterin to 7,8-dihydrobiopterin in endothelial cells determines glucose-elicited changes in NO vs. superoxide production by eNOS. Am J Physiol Heart Circ Physiol. 2008; 294: H1530-H1540. (Pubitemid 351492501)
18. Crabtree MJ, Tatham AL, Al-Wakeel Y, Warrick N, Hale AB, Cai S, Channon KM, Alp NJ. Quantitative regulation of intracellular endothelial nitric oxide synthase (eNOS) coupling by both tetrahydrobiopterin-eNOS stoichiometry and biopterin redox status: insights from cells with tetregulated GTP cyclohydrolase I expression. J Biol Chem. 2009; 284: 1136-1144.
19. Vasquez-Vivar J, Martasek P, Whitsett J, Joseph J, Kalyanaraman B. The ratio between tetrahydrobiopterin and oxidized tetrahydrobiopterin analogues controls superoxide release from endothelial nitric oxide synthase: an EPR spin trapping study. Biochem J. 2002; 362: 733-739. (Pubitemid 34242326)
20. Antoniades C, Shirodaria C, Warrick N, Cai S, de Bono J, Lee J, Leeson P, Neubauer S, Ratnatunga C, Pillai R, Refsum H, Channon KM. 5- Methyltetrahydrofolate rapidly improves endothelial function and decreases superoxide production in human vessels: effects on vascular tetrahydrobiopterin availability and endothelial nitric oxide synthase coupling. Circulation. 2006; 114: 1193-1201. (Pubitemid 44386484)
21. Kuzkaya N, Weissmann N, Harrison DG, Dikalov S. Interactions of peroxynitrite, tetrahydrobiopterin, ascorbic acid, and thiols: implications for uncoupling endothelial nitric-oxide synthase. J Biol Chem. 2003; 278: 22546-22554. (Pubitemid 36830310)
22. Shirodaria C, Antoniades C, Lee J, Jackson CE, Robson MD, Francis JM, Moat SJ, Ratnatunga C, Pillai R, Refsum H, Neubauer S, Channon KM. Global improvement of vascular function and redox state with low-dose folic acid: implications for folate therapy in patients with coronary artery disease. Circulation. 2007; 115: 2262-2270. (Pubitemid 46685894)
23. Sawabe K, Wakasugi KO, Hasegawa H. Tetrahydrobiopterin uptake in supplemental administration: elevation of tissue tetrahydrobiopterin in mice following uptake of the exogenously oxidized product 7,8-dihydrobiopterin and subsequent reduction by an anti-folate-sensitive process. J Pharmacol Sci. 2004; 96: 124-133. (Pubitemid 39469603)
24. Sawabe K, Suetake Y, Wakasugi KO, Hasegawa H. Accumulated BH4 in mouse liver caused by administration of either 6R-or 6SBH4 consisted solely of the 6R-diastereomer: evidence of oxidation to BH2 and enzymic reduction. Mol Genet Metab. 2005; 86(suppl 1): S145-S147. (Pubitemid 41771125)
25. Crabtree MJ, Tatham AL, Hale AB, Alp NJ, Channon KM. Critical role for tetrahydrobiopterin recycling by dihydrofolate reductase in regulation of endothelial nitric-oxide synthase coupling: relative importance of the de novo biopterin synthesis versus salvage pathways. J Biol Chem. 2009; 284: 28128-28136.
26. Crabtree MJ, Hale AB, Channon KM. Dihydrofolate reductase protects endothelial nitric oxide synthase from uncoupling in tetrahydrobiopterin deficiency. Free Radic Biol Med. 2011; 50: 1639-1646.
27. Chalupsky K, Cai H. Endothelial dihydrofolate reductase: critical for nitric oxide bioavailability and role in angiotensin II uncoupling of endothelial nitric oxide synthase. Proc Natl Acad Sci U S A. 2005; 102: 9056-9061. (Pubitemid 40881077)
28. Gao L, Chalupsky K, Stefani E, Cai H. Mechanistic insights into folic acid-dependent vascular protection: dihydrofolate reductase (DHFR)-mediated reduction in oxidant stress in endothelial cells and angiotensin II-infused mice: a novel HPLC-based fluorescent assay for DHFR activity. J Mol Cell Cardiol. 2009; 47: 752-760.
29. Tsutsui M, Milstien S, Katusic ZS. Effect of tetrahydrobiopterin on endothelial function in canine middle cerebral arteries. Circ Res. 1996; 79: 336-342. (Pubitemid 26255888)
30. Antoniades C, Bakogiannis C, Tousoulis D, Reilly S, Zhang MH, Paschalis A, Antonopoulos AS, Demosthenous M, Miliou A, Psarros C, Marinou K, Sfyras N, Economopoulos G, Casadei B, Channon KM, Stefanadis C. Preoperative atorvastatin treatment in CABG patients rapidly improves vein graft redox state by inhibition of Rac1 and NADPH-oxidase activity. Circulation. 2010; 122: S66-S73.
31. Antoniades C, Bakogiannis C, Leeson P, Guzik TJ, Zhang MH, Tousoulis D, Antonopoulos AS, Demosthenous M, Marinou K, Hale A, Paschalis A, Psarros C, Triantafyllou C, Bendall J, Casadei B, Stefanadis C, Channon KM. Rapid, direct effects of statin treatment on arterial redox state and nitric oxide bioavailability in human atherosclerosis via tetrahydrobiopterin-mediated endothelial nitric oxide synthase coupling. Circulation. 2011; 124: 335-345.