Therapeutic Implications of PPARgamma in Cardiovascular Diseases.
Peroxisome proliferator-activated receptor-gamma (PPARgamma) is the members of the nuclear receptor superfamily as a master transcriptional factor that promotes differentiation of preadipocytes by activating adipose-specific gene expression. Although PPARgamma is expressed predominantly in adipose tissue and associated with adipocyte differentiation and glucose homeostasis, PPARgamma is also present in a variety of cell types including vascular cells and cardiomyocytes. Activation of PPARgamma suppresses production of inflammatory cytokines, and there is accumulating data that PPARgamma ligands exert antihypertrophy of cardiomyocytes and anti-inflammatory, antioxidative, and antiproliferative effects on vascular wall cells and cardiomyocytes. In addition, activation of PPARgamma is implicated in the regulation of endothelial function, proliferation and migration of vascular smooth muscle cells, and activation of macrophages. Many studies suggest that PPARgamma ligands not only ameliorate insulin sensitivity, but also have pleiotropic effects on the pathophysiology of atherosclerosis, cardiac hypertrophy, ischemic heart, and myocarditis.
Hasegawa
Hiroshi
H
Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Takano
Hiroyuki
H
Komuro
Issei
I
Int J Cardiol. 2009 Jan 24;131(3):298-304
18684530
Cell Metab. 2007 Aug;6(2):137-43
17681149
Lancet. 2005 Oct 8;366(9493):1279-89
16214598
Arteriosclerosis. 1984 Jul-Aug;4(4):323-40
6466191
Am J Cardiol. 2003 May 22;91(10A):9G-14G
12781903
Circ Res. 2000 Sep 29;87(7):596-602
11009565
J Am Coll Cardiol. 2007 May 1;49(17):1772-80
17466227
Cell. 2004 Feb 20;116(4):511-26
14980219
Diabetes Care. 2005 Jul;28(7):1547-54
15983299
Circulation. 2000 Oct 10;102(15):1834-9
11023940
Diabetes Res Clin Pract. 2008 Oct;82(1):48-57
18775581
Circulation. 2003 Mar 18;107(10):1350-4
12642352
Am Heart J. 2008 Apr;155(4):712-7
18371481
Prog Cardiovasc Dis. 2006 Mar-Apr;48(5):326-41
16627048
Pharmacol Ther. 2009 Jun;122(3):246-63
19318113
Nature. 2005 Sep 29;437(7059):759-63
16127449
Diabetes Care. 2001 Feb;24(2):392-7
11213897
Diabetes Care. 2002 Nov;25(11):2058-64
12401757
Circulation. 2003 Apr 22;107(15):1954-7
12695287
Circ Res. 1998 Nov 30;83(11):1097-103
9831704
Cardiovasc Res. 2003 Sep 1;59(3):685-94
14499870
Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12097-102
11035776
Lab Invest. 2001 Jul;81(7):929-36
11454980
JAMA. 2007 Sep 12;298(10):1189-95
17848653
J Clin Oncol. 2004 Jul 15;22(14):2918-26
15254061
Cell Signal. 2006 Oct;18(10):1801-12
16531007
Circulation. 2002 May 14;105(19):2296-302
12010913
Nat Med. 2005 Aug;11(8):861-6
16007095
Lancet. 2007 Sep 29;370(9593):1129-36
17905165
Circulation. 2001 Jul 24;104(4):455-60
11468209
Circ Res. 1999 Sep 3;85(5):394-402
10473669
Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7614-9
9636198
Cardiovasc Res. 2004 Jul 1;63(1):51-9
15194461
Ann Thorac Surg. 2003 Feb;75(2):S644-8
12607706
JAMA. 2006 Dec 6;296(21):2572-81
17101640
Cell. 1998 Apr 17;93(2):241-52
9568716
Circulation. 2002 Mar 12;105(10):1152-4
11889005
Hypertens Res. 2002 Jul;25(4):491-8
12358132
J Clin Invest. 1996 Oct 15;98(8):1897-905
8878442
Circ Res. 2004 May 14;94(9):1168-78
15142970
Am J Hypertens. 2000 Jan;13(1 Pt 1):74-82
10678274
Clin Trials. 2008;5(2):116-20
18375649
Diabetes. 2002 May;51(5):1507-14
11978649
Circ J. 2008 Apr;72(4):551-7
18362424
N Engl J Med. 1999 Jan 14;340(2):115-26
9887164
Diabetes Obes Metab. 2008 Dec;10(12):1221-38
18505403
Circulation. 2000 Jan 25;101(3):235-8
10645917
Nature. 1998 Jan 1;391(6662):79-82
9422508
Cardiovasc Res. 2002 Jan;53(1):31-47
11744011
N Engl J Med. 2007 Jun 14;356(24):2457-71
17517853
Diabetes Metab. 2004 Feb;30(1):7-12
15029092
J Cardiovasc Pharmacol. 1999 May;33(5):798-806
10226869
Proc Natl Acad Sci U S A. 2004 Oct 5;101(40):14461-6
15452344
Circ Res. 2000 Sep 15;87(6):516-21
10988245
Eur J Pharmacol. 2000 Nov 3;407(3):227-35
11068018
Circulation. 2002 Mar 12;105(10):1240-6
11889020
Circ J. 2007 Mar;71(3):338-42
17322631
Circulation. 2003 Dec 9;108(23):2941-8
14662691
Am J Hypertens. 2005 May;18(5 Pt 1):720-30
15882557
J Mol Cell Cardiol. 2005 Feb;38(2):257-65
15698832
Diabetes. 2007 Oct;56(10):2609-15
17623816
Nature. 1998 Jan 1;391(6662):82-6
9422509
Acta Physiol (Oxf). 2007 Nov;191(3):171-88
17935522
Cardiovasc Drugs Ther. 1997 May;11 Suppl 1:199-212
9211012
Circ Res. 2002 Apr 5;90(6):703-10
11934839
Hypertension. 2004 May;43(5):993-1002
15007034
Cell. 1998 Apr 17;93(2):229-40
9568715
Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9406-11
15956187
Arterioscler Thromb Vasc Biol. 2003 Jan 1;23(1):45-51
12524223
Circulation. 2001 Oct 2;104(14):1670-5
11581147
Circulation. 2000 Mar 14;101(10):1165-71
10715264
Diabetes. 1997 Mar;46(3):433-9
9032099
Eur J Pharmacol. 2000 Aug 11;401(3):259-70
10936484
J Biol Chem. 2000 Jan 14;275(2):1241-6
10625669
Am J Pathol. 1998 Jul;153(1):17-23
9665460
Circulation. 2001 Nov 20;104(21):2588-94
11714655
Circ J. 2008 Jun;72(6):998-1002
18503229
Cardiovasc Res. 2007 Nov 1;76(2):269-79
17678635
Physiol Genomics. 2002 Oct 02;11(1):21-30
12361987
Nat Rev Cardiol. 2010 Jan;7(1):30-7
19949426
Cardiol Clin. 2001 Nov;19(4):541-5
11715175
Nature. 2007 Jun 28;447(7148):1116-20
17515919
J Am Coll Cardiol. 2008 Sep 2;52(10):869-81
18755353
Science. 2000 Sep 1;289(5484):1524-9
10968783
J Biol Chem. 2004 Jan 9;279(2):1304-9
14557259
Endocrinology. 2001 Jul;142(7):3125-34
11416035
N Engl J Med. 2008 Apr 10;358(15):1547-59
18378520
Atherosclerosis. 2009 Aug;205(2):376-84
19193378
FASEB J. 2002 Jul;16(9):1027-40
12087064
Am J Cardiol. 2004 Jun 15;93(12):1569-72
15194042
JAMA. 2008 Apr 2;299(13):1561-73
18378631
Am Heart J. 2008 Jul;156(1):23-30
18585493
J Biol Chem. 2000 Sep 8;275(36):28240-5
10858438
J Biol Chem. 2001 Apr 20;276(16):12893-7
11278956
Nature. 1999 Jul 22;400(6742):378-82
10432118
BMC Med Res Methodol. 2008 May 30;8:34
18513392
Stroke. 2007 Mar;38(3):865-73
17290029
Ann Intern Med. 2007 Oct 16;147(8):578-81
17679700
Int J Cardiol. 2008 Nov 12;130(2):131-9
18582964
Biomed Pharmacother. 2002 Oct;56(8):407-10
12442913
Arterioscler Thromb Vasc Biol. 1999 Sep;19(9):2094-104
10479650
Circ Res. 2005 Aug 19;97(4):372-9
16051889
Circulation. 2002 Dec 10;106(24):3126-32
12473562
Hypertension. 2005 Jul;46(1):137-43
15939809
Mol Cell. 2001 Jan;7(1):161-71
11172721
Lancet. 2008 May 3;371(9623):1513-8
18456100
J Am Coll Cardiol. 2007 Apr 24;49(16):1696-704
17448371
Am J Pathol. 1992 Dec;141(6):1427-33
1281621
N Engl J Med. 1999 Aug 12;341(7):498-511
10441607
Biochem Biophys Res Commun. 1998 Jun 18;247(2):353-6
9642130
FASEB J. 2006 Jun;20(8):1203-5
16672634
Diabetes Res Clin Pract. 2007 May;76(2):279-89
17055103
J Clin Invest. 2007 Oct;117(10):2791-801
17823655
Nat Med. 2001 Jan;7(1):53-8
11135616
Clin Chem. 1999 Aug;45(8 Pt 2):1339-45
10430816