Tetrahydrobiopterin: pleiotropic roles in cardiovascular pathophysiology

被引：43

作者：

Cunnington, Colin ^{[1
]}

Channon, Keith M. ^{[1
]}

机构：

[1] Univ Oxford, Dept Cardiovasc Med, John Radcliffe Hosp, Oxford OX3 9DU, England

来源：

HEART | 2010年 / 96卷 / 23期

关键词：

NITRIC-OXIDE SYNTHASE; ENDOTHELIUM-DEPENDENT VASODILATION; CORONARY-ARTERY-DISEASE; VASCULAR SUPEROXIDE-PRODUCTION; ISCHEMIA-REPERFUSION INJURY; PULMONARY-HYPERTENSION; CARDIAC-HYPERTROPHY; GTP-CYCLOHYDROLASE; DIABETES-MELLITUS; CONSCIOUS RABBITS;

D O I：

10.1136/hrt.2009.180430

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Tetrahydrobiopterin (BH4) functions as a cofactor in several important enzyme systems. Substantial evidence implicates BH4 as a key regulator of endothelial nitric oxide synthase (eNOS) in the setting of endothelial dysfunction and atherosclerosis. Investigators have now taken early steps in addressing the potential of BH4 as a therapeutic strategy. However, it has become more apparent that the role of BH4 in other enzymatic pathways, including other NOS isoforms and the aromatic amino acid hydroxylases, may have a bearing on important aspects of cardiovascular homeostasis. Together with eNOS, these enzymes may play key roles in diverse cardiovascular disease states such as ischaemia-reperfusion injury, cardiac hypertrophy, cardiac autonomic function and pulmonary hypertension. This review provides an overview of the role of BH4 in cardiovascular pathophysiology.

引用

页码：1872 / 1877

页数：6

共 48 条

[1] Regulation of endothelial nitric oxide synthase by tetrahydrobiopterin in vascular disease [J].

Alp, NJ ;

Channon, KM .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2004, 24 (03) :413-420

[2] GCH1 haplotype determines vascular and plasma biopterin availability in coronary artery disease -: Effects on vascular superoxide production and endothelial function [J].

Antoniades, Charalambos ;

Shirodaria, Cheerag ;

Van Assche, Tim ;

Cunnington, Colin ;

Tegeder, Irmgard ;

Loetsch, Joern ;

Guzik, Tomasz J. ;

Leeson, Paul ;

Diesch, Jonathan ;

Tousoulis, Dimitris ;

Stefanadis, Christodoulos ;

Costigan, Michael ;

Woolf, Clifford J. ;

Alp, Nicholas J. ;

Channon, Keith M. .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2008, 52 (02) :158-165

[3] Altered plasma versus vascular biopterins in human atherosclerosis reveal relationships between endothelial nitric oxide synthase coupling, endothelial function, and inflammation [J].

Antoniades, Charalambos ;

Shirodaria, Cheerag ;

Crabtree, Mark ;

Rinze, Ruth ;

Alp, Nicholas ;

Cunnington, Colin ;

Diesch, Jonathan ;

Tousoulis, Dimitris ;

Stefanadis, Christodoulos ;

Leeson, Paul ;

Ratnatunga, Chandi ;

Pillai, Ravi ;

Channon, Keith M. .

CIRCULATION, 2007, 116 (24) :2851-2859

[4] 5-methyltetrahydrofolate rapidly improves endothelial function and decreases superoxide production in human vessels - Effects on vascular tetrahydrobiopterin availability and endothelial nitric oxide synthase coupling [J].

Antoniades, Charalambos ;

Shirodaria, Cheerag ;

Warrick, Nicholas ;

Cai, Shijie ;

de Bono, Joseph ;

Lee, Justin ;

Leeson, Paul ;

Neubauer, Stefan ;

Ratnatunga, Chandi ;

Pillai, Ravi ;

Refsum, Helga ;

Channon, Keith M. .

CIRCULATION, 2006, 114 (11) :1193-1201

[5] Inhibition of tetrahydrobiopterin synthesis reduces in vivo nitric oxide production in experimental endotoxic shock [J].

Bune, AJ ;

Brand, MP ;

Heales, SJR ;

Shergill, JK ;

Cammack, R ;

Cook, HT .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1996, 220 (01) :13-19

[6] Adenoviral gene transfer of endothelial nitric-oxide synthase (eNOS) partially restores normal pulmonary arterial pressure in eNOS-deficient mice [J].

Champion, HC ;

Bivalacqua, TJ ;

Greenberg, SS ;

Giles, TD ;

Hyman, AL ;

Kadowitz, PJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (20) :13248-13253

[7] Role of nitric oxide in the regulation of cardiovascular autonomic control [J].

Chowdhary, S ;

Townend, JN .

CLINICAL SCIENCE, 1999, 97 (01) :5-17

[8] Chronic treatment with tetrahydrobiopterin reverses endothelial dysfunction and oxidative stress in hypercholesterolaemia [J].

Cosentino, F. ;

Huerlimann, D. ;

Gatti, C. Delli ;

Chenevard, R. ;

Blau, N. ;

Alp, N. J. ;

Channon, K. M. ;

Eto, M. ;

Lerch, P. ;

Enseleit, F. ;

Ruschitzka, F. ;

Volpe, M. ;

Luescher, T. F. ;

Noll, G. .

HEART, 2008, 94 (04) :487-492

[9] Clinical genetics of functionally mild non-coding GTP cyclohydrolase 1 (GCH1) polymorphisms modulating pain and cardiovascular risk [J].

Doehring, Alexandra ;

Antoniades, Charalambos ;

Channon, Keith M. ;

Tegeder, Irmgard ;

Loetsch, Joern .

MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH, 2008, 659 (03) :195-201

[10] Myocardial ischemia results in tetrahydrobiopterin (BH4) oxidation with impaired endothelial function ameliorated by BH4 [J].

Dumitrescu, Cristian ;

Biondi, Roberto ;

Xia, Yong ;

Cardounel, Arturo J. ;

Druhan, Lawrence J. ;

Ambrosio, Giuseppe ;

Zweier, Jay L. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (38) :15081-15086

← 1 2 3 4 5 →