title: Effects of ACE2 inhibition in the post-myocardial infarction heart.
abstract: BACKGROUND
  There is evidence that angiotensin-converting enzyme 2 (ACE2) is cardioprotective. To assess this in the post-myocardial infarction (MI) heart, we treated adult male Sprague-Dawley rats with either placebo (PL) or C16, a selective ACE2 inhibitor, after permanent coronary artery ligation or sham operation.
  
  
  RESULTS
  Coronary artery ligation resulting in MI between 25% to 50% of the left ventricular (LV) circumference caused substantial cardiac remodeling. Daily C16 administration from postoperative days 2 to 28 at a dose that inhibited myocardial ACE2 activity was associated with a significant increase in MI size and reduction in LV % fractional shortening. Treatment with C16 did not significantly affect post-MI increases in LV end-diastolic dimension but did inhibit increases in wall thickness and fibrosis in non-infarcted LV. On postoperative day 7, C16 had no significant effect on the increased level of apoptosis in the infarct and border zones nor did it significantly affect capillary density surrounding the MI. It did, however, significantly reduce the number of c-kit(+) cells in the border region.
  
  
  CONCLUSIONS
  These findings support the notion that ACE2 exerts cardioprotective effects by preserving jeopardized cardiomyocytes in the border zone. The reduction in hypertrophy and fibrosis with C16, however, suggests that ACE2 activity has diverse effects on post-MI remodeling.
authors.affiliation: Seoul National University, Seoul, Korea.
authors.forename: Myung-A
authors.initials: MA
authors.lastname: Kim
authors.forename: Dongheon
authors.initials: D
authors.lastname: Yang
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kida
authors.forename: Natalia
authors.initials: N
authors.lastname: Molotkova
authors.forename: Seon Ju
authors.initials: SJ
authors.lastname: Yeo
authors.forename: Nissi
authors.initials: N
authors.lastname: Varki
authors.forename: Michikado
authors.initials: M
authors.lastname: Iwata
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Dalton
authors.forename: Kirk L
authors.initials: KL
authors.lastname: Peterson
authors.forename: Wolf-Eberhard
authors.initials: WE
authors.lastname: Siems
authors.forename: Thomas
authors.initials: T
authors.lastname: Walther
authors.forename: Randy T
authors.initials: RT
authors.lastname: Cowling
authors.forename: John
authors.initials: J
authors.lastname: Kjekshus
authors.forename: Barry
authors.initials: B
authors.lastname: Greenberg
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D005355:Fibrosis / Q000503:physiopathology; D006346:Heart Septum / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology*; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System; D013997:Time Factors; D014463:Ultrasonography
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2
references.citation: Am J Physiol. 1991 May;260(5 Pt 2):H1406-14
references.pmid: 2035662
references.citation: J Am Coll Cardiol. 2008 Aug 26;52(9):750-4
references.pmid: 18718423
references.citation: J Cardiovasc Pharmacol. 1999 Mar;33(3):433-9
references.pmid: 10069680
references.citation: Hypertension. 2008 Mar;51(3):712-8
references.pmid: 18250366
references.citation: Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10344-9
references.pmid: 11504914
references.citation: Circulation. 2001 Jun 12;103(23):2845-50
references.pmid: 11401943
references.citation: Circ Res. 2000 Sep 1;87(5):E1-9
references.pmid: 10969042
references.citation: Circulation. 2002 Apr 2;105(13):1548-50
references.pmid: 11927520
references.citation: Circ Res. 2001 May 11;88(9):961-8
references.pmid: 11349007
references.citation: J Am Chem Soc. 2002 Oct 9;124(40):11852-3
references.pmid: 12358520
references.citation: Circulation. 2003 Oct 7;108(14):1707-12
references.pmid: 14504186
references.citation: J Mol Cell Cardiol. 2007 Oct;43(4):377-87
references.pmid: 17716688
references.citation: Eur Heart J. 2005 Feb;26(4):369-75; discussion 322-4
references.pmid: 15671045
references.citation: Circ Res. 1999 Oct 1;85(7):643-50
references.pmid: 10506489
references.citation: BMC Med. 2004 May 19;2:19
references.pmid: 15151696
references.citation: Circulation. 1997 Dec 2;96(11):4065-82
references.pmid: 9403633
references.citation: FEBS Lett. 2002 Dec 4;532(1-2):107-10
references.pmid: 12459472
references.citation: N Engl J Med. 1992 Sep 3;327(10):669-77
references.pmid: 1386652
references.citation: J Am Coll Cardiol. 1999 Feb;33(2):565-71
references.pmid: 9973040
references.citation: Am J Physiol. 1995 Sep;269(3 Pt 1):E426-37
references.pmid: 7573419
references.citation: Nature. 2002 Jun 20;417(6891):822-8
references.pmid: 12075344
references.citation: J Biol Chem. 2002 Apr 26;277(17):14838-43
references.pmid: 11815627
references.citation: Lab Invest. 1996 Jan;74(1):86-107
references.pmid: 8569201
references.citation: Circulation. 1995 May 15;91(10):2573-81
references.pmid: 7743619
references.citation: Circ Res. 1985 Jul;57(1):84-95
references.pmid: 3891127
references.citation: Hypertension. 1996 Mar;27(3 Pt 2):523-8
references.pmid: 8613197
references.citation: Trends Endocrinol Metab. 2004 May-Jun;15(4):166-9
references.pmid: 15109615
references.citation: J Mol Cell Cardiol. 2005 Mar;38(3):505-15
references.pmid: 15733910
references.citation: Circulation. 1990 Apr;81(4):1161-72
references.pmid: 2138525
references.citation: J Cardiovasc Pharmacol. 2002 Nov;40(5):693-700
references.pmid: 12409978
references.citation: Hypertension. 2009 Apr;53(4):694-700
references.pmid: 19221212
references.citation: Hypertension. 1996 Jul;28(1):104-8
references.pmid: 8675248
references.citation: Am J Physiol Heart Circ Physiol. 2005 Oct;289(4):H1560-6
references.pmid: 15951342
references.citation: Br Heart J. 1986 Jun;55(6):575-81
references.pmid: 3718796
references.citation: N Engl J Med. 1988 Jul 14;319(2):80-6
references.pmid: 2967917
references.citation: Circulation. 2003 Oct 7;108(14):1679-81
references.pmid: 14504185
references.citation: Exp Physiol. 2005 Sep;90(5):783-90
references.pmid: 16049057
references.citation: J Biol Chem. 2000 Oct 27;275(43):33238-43
references.pmid: 10924499
references.citation: Hypertension. 1999 Jan;33(1 Pt 2):207-11
references.pmid: 9931106
references.citation: Hypertension. 1995 Jun;25(6):1252-9
references.pmid: 7768570
references.citation: Am J Physiol Heart Circ Physiol. 2005 Dec;289(6):H2356-63
references.pmid: 16024575
references.citation: Hypertension. 2006 Apr;47(4):718-26
references.pmid: 16505206
references.citation: J Cardiovasc Pharmacol. 2005 Sep;46(3):274-9
references.pmid: 16116331
references.citation: Cell. 2003 Sep 19;114(6):763-76
references.pmid: 14505575
references.citation: J Biol Chem. 2003 May 2;278(18):15532-40
references.pmid: 12606557
references.citation: Circulation. 2001 Feb 6;103(5):736-42
references.pmid: 11156887
references.citation: J Clin Invest. 2006 Aug;116(8):2218-25
references.pmid: 16878172
references.citation: N Engl J Med. 1995 Dec 21;333(25):1670-6
references.pmid: 7477219