Protein targets of inflammatory serine proteases and cardiovascular disease.
Serine proteases are a key component of the inflammatory response as they are discharged from activated leukocytes and mast cells or generated through the coagulation cascade. Their enzymatic activity plays a major role in the body's defense mechanisms but it has also an impact on vascular homeostasis and tissue remodeling. Here we focus on the biological role of serine proteases in the context of cardiovascular disease and their mechanism(s) of action in determining specific vascular and tissue phenotypes. Protease-activated receptors (PARs) mediate serine protease effects; however, these proteases also exert a number of biological activities independent of PARs as they target specific protein substrates implicated in vascular remodeling and the development of cardiovascular disease thus controlling their activities. In this review both PAR-dependent and -independent mechanisms of action of serine proteases are discussed for their relevance to vascular homeostasis and structural/functional alterations of the cardiovascular system. The elucidation of these mechanisms will lead to a better understanding of the molecular forces that control vascular and tissue homeostasis and to effective preventative and therapeutic approaches.
Sharony
Ram
R
Department of Cardiothoracic Surgery, New York University School of Medicine, 530 First Avenue, New York, NY 10016, USA. pintug01@nyumc.org.
Yu
Pey-Jen
PJ
Park
Joy
J
Galloway
Aubrey C
AC
Mignatti
Paolo
P
Pintucci
Giuseppe
G
Proc Natl Acad Sci U S A. 1989 Jun;86(11):3978-81
2726761
Am J Pathol. 1998 Feb;152(2):353-8
9466560
Arterioscler Thromb Vasc Biol. 2004 Feb;24(2):270-5
14684425
J Thromb Haemost. 2003 Jul;1(7):1504-14
12871286
Circulation. 2003 Jan 28;107(3):398-404
12551862
Circ Res. 2008 Jan 4;102(1):32-41
17975113
Immunity. 1998 Mar;8(3):383-90
9529155
J Biol Chem. 2008 Sep 19;283(38):25871-8
18650426
Curr Med Chem Cardiovasc Hematol Agents. 2005 Jan;3(1):33-44
15638742
Trends Genet. 2004 Nov;20(11):563-9
15475116
J Biol Chem. 1994 Apr 1;269(13):9416-9
8144524
Naunyn Schmiedebergs Arch Pharmacol. 2008 Jun;377(4-6):377-92
17952408
J Biol Chem. 1999 Dec 17;274(51):36328-34
10593924
Arterioscler Thromb Vasc Biol. 1998 Jun;18(6):915-21
9633931
Circulation. 1983 May;67(5):1016-23
6831665
J Immunol. 1989 Jul 1;143(1):168-73
2499627
J Biol Chem. 1995 Oct 6;270(40):23688-92
7559538
Kidney Int. 1994 Feb;45(2):515-24
8164440
J Biol Chem. 2000 Dec 29;275(52):40671-8
11005807
Blood. 2010 Jun 17;115(24):4981-90
20233968
Am J Respir Cell Mol Biol. 1993 Oct;9(4):455-62
7691110
Circulation. 2002 Apr 23;105(16):1890-6
11997273
Thromb Res. 2009 May;124(1):84-9
19201454
J Biol Chem. 2003 Jun 27;278(26):23944-54
12707281
J Immunol. 2002 Aug 1;169(3):1467-73
12133973
Nature. 1997 Sep 11;389(6647):183-6
9296496
Semin Thromb Hemost. 1998;24(2):145-50
9579635
Clin Sci (Lond). 1987 Mar;72(3):373-81
2434283
Crit Care. 2009;13 Suppl 5:S12
19951384
J Thromb Haemost. 2005 Aug;3(8):1800-14
16102047
Am J Pathol. 2007 Mar;170(3):930-40
17322378
J Cardiovasc Pharmacol. 1997 Nov;30(5):649-57
9388048
FASEB J. 2004 May;18(7):920-2
15033932
Blood. 2005 Apr 15;105(8):3178-84
15626732
Biochem Soc Trans. 2005 Apr;33(Pt 2):331-4
15787599
Mol Cell Biol. 1995 Jan;15(1):35-44
7799942
Arterioscler Thromb Vasc Biol. 1997 Jan;17(1):188-93
9012655
Dent Mater J. 2004 Dec;23(4):650-5
15688734
J Cardiovasc Pharmacol. 1993 Oct;22(4):609-16
7505364
Circ Res. 2005 Feb 4;96(2):172-9
15625285
Am J Physiol. 1997 Apr;272(4 Pt 1):C1112-22
9142835
Nat Med. 1998 Aug;4(8):909-14
9701242
J Immunol. 1991 Dec 1;147(11):3862-8
1940372
Am J Pathol. 1996 Nov;149(5):1617-26
8909251
J Interferon Cytokine Res. 1999 Nov;19(11):1277-87
10574621
Circ Res. 1991 Sep;69(3):871-80
1873879
J Clin Invest. 1992 Oct;90(4):1614-21
1328304
Br J Pharmacol. 2004 Oct;143(4):443-54
15451771
J Cell Sci. 2002 Jun 15;115(Pt 12):2475-84
12045218
Trends Mol Med. 2008 Oct;14(10):429-40
18774340
J Biol Chem. 2010 Mar 12;285(11):7929-37
20071328
J Biol Chem. 1993 Mar 15;268(8):5724-7
8449935
Nature. 1994 Apr 14;368(6472):648-51
8145852
Connect Tissue Res. 1993;30(1):1-9
8149741
Ann N Y Acad Sci. 1986;485:293-309
3032047
FASEB J. 2009 Sep;23(9):3129-39
19417089
J Am Soc Nephrol. 2002 Dec;13(12):2840-9
12444202
J Appl Physiol (1985). 2001 Sep;91(3):1372-9
11509538
J Clin Invest. 1997 Jun 1;99(11):2682-90
9169498
Arterioscler Thromb. 1994 Oct;14(10):1648-56
7918316
Clin Exp Immunol. 1988 Jul;73(1):139-45
3168329
J Clin Invest. 2003 Jul;112(2):181-8
12865407
Am J Physiol. 1989 May;256(5 Pt 2):F794-802
2541628
J Cell Physiol. 1995 Jun;163(3):510-22
7775594
Blood. 1999 Dec 15;94(12):4156-65
10590060
Am J Physiol Heart Circ Physiol. 2006 Apr;290(4):H1651-9
16284240
Immunology. 1993 Sep;80(1):134-9
8244455
Nature. 1991 Oct 17;353(6345):674-7
1717851
J Biol Chem. 1995 Mar 3;270(9):4689-96
7876240
Nat Rev Cancer. 2004 Nov;4(11):876-90
15516960
Circulation. 2009 Nov 3;120(18):1800-13
19841301
J Leukoc Biol. 2005 Aug;78(2):442-52
15923218
Brain. 2002 Jun;125(Pt 6):1283-96
12023317
Hypertension. 2004 May;43(5):924-31
15007038
J Lab Clin Med. 1986 Oct;108(4):294-300
3639117
J Cell Biochem. 2007 Apr 1;100(5):1100-8
17131363
Arterioscler Thromb Vasc Biol. 2005 Oct;25(10):2062-8
16123319
Cell. 2000 Oct 13;103(2):211-25
11057895
Surgery. 1999 Aug;126(2):422-7
10455916
Can J Physiol Pharmacol. 1995 Aug;73(8):1203-7
8564891
FASEB J. 1991 Aug;5(11):2529-37
1868978
J Hypertens. 2004 Jan;22(1):157-66
15106807
Hum Mutat. 2009 Sep;30(9):1245-55
19621416
J Biol Chem. 1999 Aug 20;274(34):23969-76
10446165
Eur Heart J. 2006 Jun;27(12):1495-504
16401677
Ann N Y Acad Sci. 1995 Apr 21;760:354-6
7785915
Trends Pharmacol Sci. 2001 Mar;22(3):146-52
11239578
J Cell Physiol. 2001 Nov;189(2):197-206
11598905
Circulation. 2003 Aug 5;108(5):512-5
12874178
J Biol Chem. 1971 Dec 10;246(23):7265-74
5167021
Immunity. 1999 Sep;11(3):359-67
10514014
J Immunol. 1998 Sep 1;161(5):2533-40
9725253
Arterioscler Thromb Vasc Biol. 2004 Jan;24(1):41-53
14551154
Circ Res. 2000 Jul 21;87(2):92-8
10903991
Circ Res. 1998 May 18;82(9):980-7
9598595
Circ Res. 2006 Jun 23;98(12):1479-89
16709900
Diabetes Res. 1989 Mar;10(3):135-8
2805587
Arterioscler Thromb Vasc Biol. 2006 Jan;26(1):e1-2
16373617
Blood. 2004 Sep 15;104(6):1740-4
15178575
Arterioscler Thromb Vasc Biol. 2007 Nov;27(11):2302-9
17717292
Clin Chim Acta. 2003 Jun;332(1-2):51-9
12763280
Arterioscler Thromb Vasc Biol. 2003 Jun 1;23(6):1029-34
12730087
Circulation. 2003 Oct 7;108(14):1676-8
14504187
Am J Physiol Cell Physiol. 2006 Jan;290(1):C172-82
16148030
Circulation. 2006 Mar 7;113(9):1244-54
16505172
Curr Opin Cardiol. 2002 Jul;17(4):374-9
12151872
Trends Mol Med. 2005 May;11(5):240-50
15882612
J Biol Chem. 2006 Oct 27;281(43):32095-112
16885167
Atherosclerosis. 2010 Jun;210(2):668-70
20074733
Physiol Rev. 2005 Oct;85(4):1159-204
16183910
Am J Pathol. 1995 Jul;147(1):166-75
7541609
Am J Pathol. 2001 Dec;159(6):2137-45
11733364
Crit Care. 2003 Apr;7(2):123-9
12720558
Crit Care. 2006;10(6):317
17096866
J Biol Chem. 1996 Nov 8;271(45):28485-91
8910476
Immunol Cell Biol. 2006 Apr;84(2):115-24
16519729
J Clin Invest. 1993 Jan;91(1):94-8
8380817
Circulation. 2003 Jun 10;107(22):2829-36
12771009
Kidney Int. 2006 Jul;70(2):283-97
16738538
Cell. 2005 Feb 11;120(3):303-13
15707890
Am J Physiol. 1998 Aug;275(2):H385-92
9683424
J Biol Chem. 1986 Mar 15;261(8):3486-9
3081506
Genome Res. 2004 Apr;14(4):609-22
15060002
J Cell Physiol. 1993 Sep;156(3):541-9
8360259
Pharmacol Rev. 2002 Jun;54(2):203-17
12037136
Oncogene. 2008 Apr 17;27(18):2594-601
17968311
Bioessays. 2006 May;28(5):504-14
16615083
Circulation. 2001 May 29;103(21):2531-4
11382718
Circulation. 2006 Sep 5;114(10):1070-7
16952995
J Immunol. 1998 Sep 1;161(5):2465-72
9725245
Chest. 2003 Sep;124(3 Suppl):58S-68S
12970125
Arthritis Rheum. 2009 Jul;60(7):1957-65
19565503
N Engl J Med. 1989 Feb 9;320(6):365-76
2536474
Arterioscler Thromb Vasc Biol. 2007 Apr;27(4):e20-5
17255536
Circ Res. 2004 Feb 20;94(3):340-5
14670838
Arch Med Res. 2006 May;37(4):456-60
16624642
Thromb Haemost. 1997 Jul;78(1):200-4
9198153
Br J Pharmacol. 2008 Mar;153 Suppl 1:S263-82
18059329
Mayo Clin Proc. 2006 Sep;81(9):1241-57
16970222
Blood. 1993 Jun 15;81(12):3324-31
8507869
J Exp Med. 2002 Oct 21;196(8):1047-55
12391016
J Lab Clin Med. 1993 Jul;122(1):69-79
8320493
Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):643-8
11805322
J Korean Med Sci. 2000 Oct;15(5):485-93
11068982
Am J Physiol Gastrointest Liver Physiol. 2004 Jul;287(1):G286-98
15194561
J Biol Chem. 1991 Oct 5;266(28):18846-53
1655765
J Thorac Cardiovasc Surg. 2009 Jul;138(1):196-9
19577079
J Atheroscler Thromb. 2003;10(4):211-25
14566084
Lancet. 1997 Mar 15;349(9054):769-71
9074577
Adv Immunol. 2007;95:167-255
17869614
J Biol Chem. 1971 Oct 25;246(20):6204-9
4331385
Curr Opin Lipidol. 1996 Oct;7(5):330-5
8937525
Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6393-7
19332793
Br J Cancer. 2001 Mar 2;84(5):643-50
11237385
Blood. 1993 Jul 15;82(2):513-20
8329706
Atherosclerosis. 2003 Oct;170(2):333-7
14612215
Biol Chem. 2005 Aug;386(8):801-11
16201876
Arterioscler Thromb Vasc Biol. 2007 Mar;27(3):655-60
17170369
Surgery. 2006 Feb;139(2):254-62
16455335
Biochem J. 2001 Jul 1;357(Pt 1):107-15
11415441
Am J Cardiol. 2006 Sep 15;98(6):817-20
16950193
J Biol Chem. 2009 Nov 27;284(48):32989-94
19819870
Am J Physiol Gastrointest Liver Physiol. 2001 Sep;281(3):G705-17
11518683
J Clin Invest. 1992 May;89(5):1478-84
1569186
J Immunol. 1985 Oct;135(4):2762-7
3161948
Circulation. 2002 Sep 17;106(12):1439-41
12234944
Cytokine. 1992 Sep;4(5):361-8
1420997
Cancer Res. 2003 Dec 15;63(24):9032-41
14695222
J Biol Chem. 1986 Jul 25;261(21):9579-82
2426251
Arterioscler Thromb Vasc Biol. 2005 Jul;25(7):1499-505
15845904
J Pathol. 2000 Feb;190(3):300-9
10685064
J Biol Chem. 1992 Jul 5;267(19):13146-9
1320011
N Engl J Med. 2000 Mar 23;342(12):836-43
10733371
Am J Respir Cell Mol Biol. 1991 Jun;4(6):497-503
1711351
Biol Chem. 2010 Apr;391(4):299-310
20180639
J Leukoc Biol. 2006 Dec;80(6):1395-404
16963625
Mol Cancer Res. 2004 May;2(5):257-80
15192120
J Leukoc Biol. 1999 Feb;65(2):137-50
10088596
Blood. 1992 Mar 1;79(5):1233-44
1536948
J Biol Chem. 2001 Jul 27;276(30):28261-7
11375993
J Biol Chem. 1988 Apr 5;263(10):4852-60
2832409
J Immunol. 2000 Dec 1;165(11):6553-8
11086098
FASEB J. 2002 Apr;16(6):598-600
11919166
Liver Transpl. 2009 Aug;15(8):939-47
19642132
Circulation. 2000 Apr 18;101(15):1785-91
10769278
Cell Biochem Funct. 2002 Mar;20(1):39-46
11835269
Semin Thromb Hemost. 2004 Feb;30(1):63-9
15034798
Endocr Rev. 2005 Feb;26(1):1-43
15689571