The therapeutic potential of carbon monoxide.
Carbon monoxide (CO) is increasingly being accepted as a cytoprotective and homeostatic molecule with important signalling capabilities in physiological and pathophysiological situations. The endogenous production of CO occurs through the activity of constitutive (haem oxygenase 2) and inducible (haem oxygenase 1) haem oxygenases, enzymes that are responsible for the catabolism of haem. Through the generation of its products, which in addition to CO includes the bile pigments biliverdin, bilirubin and ferrous iron, the haem oxygenase 1 system also has an obligatory role in the regulation of the stress response and in cell adaptation to injury. This Review provides an overview of the physiology of CO, summarizes the effects of CO gas and CO-releasing molecules in preclinical animal models of cardiovascular disease, inflammatory disorders and organ transplantation, and discusses the development and therapeutic options for the exploitation of this simple gaseous molecule.
Motterlini
Roberto
R
Drug Discovery and Development, Italian Institute of Technology, Via Morego 30, Genoa, Italy.
Otterbein
Leo E
LE
D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D016377:Organ Transplantation / Q000379:methods; D015398:Signal Transduction
D002248:Carbon Monoxide
Arthritis Rheum. 2008 Nov;58(11):3388-93
18975324
J Immunol. 1992 Aug 15;149(4):1416-23
1386865
Mol Pharmacol. 1987 Oct;32(4):497-504
2890093
Experientia. 1990 Dec 1;46(11-12):1202-6
2174793
Am J Physiol Gastrointest Liver Physiol. 2008 Jan;294(1):G236-44
18006605
Circ Res. 2007 Oct 26;101(9):862-4
17967796
Am J Physiol Heart Circ Physiol. 2006 Dec;291(6):H2772-8
16844915
J Nucl Med. 1983 May;24(5):431-7
6405020
FASEB J. 2004 Apr;18(6):771-2
14977880
Arterioscler Thromb Vasc Biol. 2010 Jan;30(1):98-104
19875720
J Immunol. 2001 Mar 15;166(6):4185-94
11238670
J Pharmacol Exp Ther. 2006 Sep;318(3):1315-22
16772536
Nat Med. 2003 Feb;9(2):183-90
12539038
Hypertens Res. 2007 Apr;30(4):341-8
17541213
Blood Vessels. 1991;28(1-3):52-61
1848126
FASEB J. 2004 May;18(7):854-6
15001560
Am J Physiol Gastrointest Liver Physiol. 2008 Jan;294(1):G184-91
17991708
J Cell Sci. 2007 Jan 15;120(Pt 2):299-308
17179207
Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10925-30
9380736
Liver Transpl. 2009 Nov;15(11):1458-68
19877256
Am J Physiol. 1999 Apr;276(4):L688-94
10198367
Hypertension. 2007 Dec;50(6):1040-8
17923586
J Clin Invest. 2008 Jan;118(1):239-47
18060048
J Pharmacol Exp Ther. 2007 May;321(2):656-62
17289832
Chest. 1999 Oct;116(4):1007-11
10531166
J Physiol. 1912 Jun 12;44(4):275-304
16993128
J Pharmacol Toxicol Methods. 2006 Nov-Dec;54(3):288-95
16540352
J Biol Chem. 2005 Mar 11;280(10):8714-21
15590660
Hepatology. 2002 Apr;35(4):815-23
11915027
Gastroenterology. 2003 Feb;124(2):377-91
12557144
Nat Rev Drug Discov. 2007 Nov;6(11):917-35
17948022
Hypertension. 2009 Mar;53(3):508-15
19171794
Am J Pathol. 2009 Jul;175(1):422-9
19498004
Shock. 2005 Jun;23(6):527-32
15897805
Life Sci. 2007 Apr 3;80(17):1619-26
17321552
Am J Physiol Gastrointest Liver Physiol. 2005 Sep;289(3):G607-13
15890710
Am J Physiol Heart Circ Physiol. 2004 May;286(5):H1649-53
14704226
J Clin Invest. 2007 Dec;117(12):3730-41
18037988
Diabetes. 2007 May;56(5):1240-7
17303808
Br J Pharmacol. 2005 Jul;145(6):800-10
15880142
Nat Med. 2000 Apr;6(4):422-8
10742149
J Biol Chem. 1997 Mar 28;272(13):8222-6
9079640
FASEB J. 2005 Feb;19(2):284-6
15556971
Curr Pharm Des. 2003;9(30):2525-39
14529551
FASEB J. 2004 Jul;18(10):1093-5
15132974
World J Gastroenterol. 2007 Dec 14;13(46):6183-90
18069757
FASEB J. 2005 Mar;19(3):458-60
15640283
Cardiovasc Res. 2006 Jul 15;71(2):393-401
16713591
Nat Med. 2001 May;7(5):598-604
11329062
J Exp Med. 2000 Oct 2;192(7):1015-26
11015442
Circ Res. 2007 Oct 26;101(9):919-27
17823375
J Exp Med. 2005 Jul 18;202(2):283-94
16027238
Am J Physiol Heart Circ Physiol. 2004 Nov;287(5):H2009-15
15217799
Am J Physiol Renal Physiol. 2006 Feb;290(2):F324-34
16131650
J Biol Chem. 2003 Jun 13;278(24):22061-70
12690100
J Clin Invest. 2006 Mar;116(3):808-16
16485041
Dalton Trans. 2007 May 7;(17):1651-60
17443255
Arterioscler Thromb Vasc Biol. 2010 Feb;30(2):305-12
19965783
Proc Natl Acad Sci U S A. 1968 Oct;61(2):748-55
4386763
Br J Pharmacol. 2006 Oct;149(4):345-54
16953189
Resuscitation. 2007 Feb;72(2):306-18
17092627
Ren Fail. 2007;29(5):543-8
17654315
J Cell Sci. 2006 Jun 1;119(Pt 11):2291-8
16723735
Annu Rev Pharmacol Toxicol. 1997;37:517-54
9131263
Am J Physiol Renal Physiol. 2004 Nov;287(5):F979-89
15292046
Br J Ophthalmol. 2009 Feb;93(2):254-7
18977789
J Exp Med. 2006 Sep 4;203(9):2109-19
16908624
Science. 2002 Dec 20;298(5602):2385-7
12446832
Antioxid Redox Signal. 2004 Oct;6(5):841-9
15345144
J Surg Res. 2007 Mar;138(1):121-7
17196991
Gut. 2009 Mar;58(3):347-56
19022916
J Pharmacol Exp Ther. 2009 May;329(2):641-8
19190234
Intensive Care Med. 2008 Apr;34(4):649-58
18286265
Transplantation. 2006 Jan 27;81(2):220-30
16436966
Am J Respir Cell Mol Biol. 2009 Aug;41(2):129-35
19097991
Crit Care. 2009;13(4):220
19691819
FASEB J. 2009 Apr;23(4):1023-31
19095732
World J Gastroenterol. 2008 Jan 28;14(4):547-53
18203286
J Exp Med. 2005 Dec 19;202(12):1703-13
16365149
Gut. 2003 Sep;52(9):1278-85
12912858
N Engl J Med. 2007 Mar 8;356(10):998-1008
17296824
Am J Transplant. 2010 Apr;10(4):763-772
20199500
Antioxid Redox Signal. 2007 Dec;9(12):2139-55
17854278
J Mol Cell Cardiol. 1990 Jun;22(6):687-95
2231736
Am J Physiol Renal Physiol. 2009 Jul;297(1):F19-26
19369289
J Biol Chem. 2005 Jul 8;280(27):25350-60
15863496
J Clin Invest. 2007 Feb;117(2):438-47
17256058
Pharmacol Rev. 2008 Mar;60(1):79-127
18323402
Expert Opin Ther Pat. 2009 May;19(5):663-82
19441940
Circ Res. 2003 Jul 25;93(2):e2-8
12842916
Kidney Int. 2004 Feb;65(2):564-74
14717926
Hepatology. 2003 Oct;38(4):909-18
14512878
Am J Pathol. 2003 Dec;163(6):2555-63
14633627
J Immunol. 2007 Dec 1;179(11):7840-51
18025230
Arterioscler Thromb Vasc Biol. 2004 Oct;24(10):1848-53
15308554
Am J Respir Cell Mol Biol. 2009 Jul;41(1):85-92
19097987
Circ Res. 2002 Feb 8;90(2):E17-24
11834719
Trends Biochem Sci. 2006 Nov;31(11):614-21
16996273
Mol Pharmacol. 2009 Jul;76(1):173-82
19366789
Am J Physiol Renal Physiol. 2008 Oct;295(4):F1207-12
18715939
Science. 1993 Jun 25;260(5116):1946-50
8100368
Am J Physiol Heart Circ Physiol. 2009 Oct;297(4):H1243-53
19617415
Shock. 2007 Feb;27(2):165-71
17224791
Am J Physiol Renal Physiol. 2008 Mar;294(3):F508-17
18094035
Kidney Int. 2008 Oct;74(8):1009-16
18633343
Transplantation. 2008 Feb 27;85(4):576-81
18347537
Biochemistry. 2009 Feb 24;48(7):1613-9
19183042
Anesthesiology. 2008 Jun;108(6):1025-36
18497603
Am J Pathol. 2005 Jan;166(1):27-37
15631997
Liver Int. 2009 May;29(5):650-60
18795901
Antioxid Redox Signal. 2007 Dec;9(12):2175-85
17919067
Am J Physiol Lung Cell Mol Physiol. 2003 Dec;285(6):L1270-6
12896878
Biochem Biophys Res Commun. 2006 Feb 17;340(3):935-43
16403456
J Mol Med (Berl). 2008 Mar;86(3):267-79
18034222
Free Radic Biol Med. 2008 Sep 1;45(5):562-9
18549826
Am J Physiol Heart Circ Physiol. 2009 Sep;297(3):H920-9
19561312
Kidney Int. 2006 Jan;69(2):239-47
16408112
Science. 2002 Dec 20;298(5602):2339-40
12493901
Am J Physiol Gastrointest Liver Physiol. 2008 Jul;295(1):G146-G152
18497334
FASEB J. 2005 Jan;19(1):106-8
15514102
Inflammation. 2009 Dec;32(6):364-71
19705266
Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):5191-6
16551742
J Biol Chem. 2004 Oct 22;279(43):44327-34
15280387
FASEB J. 2007 Apr;21(4):1099-106
17264172
Nature. 2003 Oct 2;425(6957):531-5
14523450
Am J Physiol Renal Physiol. 2006 Apr;290(4):F789-94
16291575
J Clin Invest. 1992 Jul;90(1):267-70
1634613
Biochem J. 1927;21(5):1068-75
16743934
Am J Pathol. 2003 Oct;163(4):1587-98
14507665
FASEB J. 2007 Nov;21(13):3450-7
17551098
Cell Cycle. 2007 Jan 1;6(1):39-43
17245120
J Vasc Surg. 2006 Jul;44(1):151-8
16828440
Nat Med. 2007 Jun;13(6):703-10
17496899
Br J Pharmacol. 2004 Jun;142(3):453-60
15148243
Surgery. 2003 Aug;134(2):285-92
12947331
Physiology (Bethesda). 2009 Feb;24:26-35
19196649
Crit Care Med. 2005 Jun;33(6):1317-26
15942350
Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):4039-43
18316727
J Heart Lung Transplant. 2007 Nov;26(11):1192-8
18022087
Cardiovasc Res. 2005 Feb 15;65(3):751-61
15664403
Pharmacol Res. 2006 Jul;54(1):24-9
16524742
Am J Physiol Heart Circ Physiol. 2007 Oct;293(4):H2501-7
17630349
Eur J Pediatr. 2005 Mar;164(3):162-5
15599764
Antioxid Redox Signal. 2002 Apr;4(2):259-70
12006177
J Cell Mol Med. 2006 Jul-Sep;10(3):650-71
16989726
J Asthma. 2009 Sep;46(7):665-9
19728202
Antioxid Redox Signal. 2002 Aug;4(4):615-24
12230873
Ann Rheum Dis. 2008 Sep;67(9):1211-7
18063671
Cardiovasc Res. 2010 May 1;86(2):338-45
20167573
J Thorac Cardiovasc Surg. 2008 Oct;136(4):1067-75
18954651
Cardiovasc Res. 2007 Jul 15;75(2):339-48
17544387
Am J Hum Genet. 2000 Jan;66(1):187-95
10631150
Am J Transplant. 2006 Oct;6(10):2243-55
16827783
Hepatology. 2003 Apr;37(4):810-23
12668974
Immunity. 2006 May;24(5):601-10
16713977
Am J Epidemiol. 2009 Sep 15;170(6):747-56
19696228
FASEB J. 2008 Sep;22(9):3380-8
18556460
Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5109-14
17360382
Cryobiology. 2009 Jun;58(3):248-55
19444967
Crit Care Med. 2005 Jun;33(6):1445-6
15942382
Physiol Rev. 2006 Apr;86(2):583-650
16601269
Expert Opin Investig Drugs. 2005 Nov;14(11):1305-18
16255672
Am J Physiol Heart Circ Physiol. 2004 Jan;286(1):H304-9
14684363
Circulation. 2010 Feb 2;121(4):537-48
20083679
J Exp Med. 2009 May 11;206(5):1167-79
19398754
J Pharmacol Exp Ther. 2007 Apr;321(1):187-94
17229879
Circ Res. 1998 Sep 7;83(5):568-77
9734480
Antimicrob Agents Chemother. 2007 Dec;51(12):4303-7
17923486
J Pharmacol Exp Ther. 2006 Dec;319(3):1265-75
16943253
Diabetes. 2005 May;54(5):1400-6
15855326
Circ Res. 2008 Nov 21;103(11):1232-40
18845810
J Surg Res. 2007 May 1;139(1):128-35
17292406
FASEB J. 2005 Dec;19(14):2045-7
16223783
J Clin Invest. 1999 Apr;103(7):1047-54
10194478
Trends Immunol. 2003 Aug;24(8):449-55
12909459
Cancer Immunol Immunother. 2007 Nov;56(11):1807-15
17440721
J Exp Med. 2003 Dec 1;198(11):1707-16
14657222