title: The physiological significance of a coronary stenosis differentially affects contractility and mitochondrial function in viable chronically dysfunctional myocardium.
abstract: The reversibility of viable dysfunctional myocardium after revascularization is variable and the reasons for this are unknown. Using 2D-DIGE, we tested the hypothesis that this could reflect the extent of molecular remodeling of myocardial tissue in the absence of infarction. Swine with a progressive left anterior descending (LAD) stenosis were studied 2 months (n = 18) or 3 months (n = 22) post-instrumentation. Coronary flow reserve (vasodilated/rest) was severely reduced at 2 months (LAD 2.6 ± 0.4 versus 5.1 ± 0.4 in normal, p < 0.05) and became critically impaired after 3 months (LAD 1.1 ± 0.2, p < 0.05 vs. 2 months). Despite progression in stenosis severity, reductions in wall thickening at 2 months (LAD 37 ± 4% vs. remote 86 ± 9%, p < 0.05) were unchanged at 3 months (LAD 32 ± 3%, p = ns). Contractile dysfunction was primarily related to reductions (LAD/normal) in contractile proteins which were not affected by stenosis severity (e.g., troponin T, 2 months 0.82 ± 0.03 vs. 0.74 ± 0.03 at 3 months, p-ns). In contrast, mitochondrial function and proteins were normal at 2 months but declined with progression to a critical stenosis (state 3 respiration at 3 months 145 ± 13 vs. 216 ± 5 ng-atoms O2 mg(-1) min(-1) at 2 months, p < 0.05). In a similar fashion, increases in stress (e.g., αB-crystalline 2.13 ± 0.2 vs. 1.17 ± 0.13 at 2 months, p < 0.05) and cytoskeletal proteins (e.g., desmin 1.63 ± 0.12 vs. 1.24 ± 0.10 at 2 months, p < 0.05) only developed with more advanced remodeling from a critical stenosis. We conclude that similar degrees of chronic contractile dysfunction can have diverse intrinsic molecular adaptations to ischemia. This spectrum of adaptations may underlie variability in the time course and extent of reversibility in viable chronically dysfunctional myocardium after revascularization.
authors: The Center for Research in Cardiovascular Medicine, University at Buffalo, Buffalo, USA.
authors: Brian J
authors: BJ
authors: Page
authors: Rebeccah F
authors: RF
authors: Young
authors: Gen
authors: G
authors: Suzuki
authors: James A
authors: JA
authors: Fallavollita
authors: John M
authors: JM
authors: Canty
mesh_terms: D000818:Animals; D023921:Coronary Stenosis / Q000503:physiopathology*; D003331:Coronary Vessels / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D006321:Heart / Q000503:physiopathology*; D008929:Mitochondria, Heart / Q000502:physiology*; D009200:Myocardial Contraction / Q000502:physiology*; D012039:Regional Blood Flow / Q000502:physiology; D012720:Severity of Illness Index; D013552:Swine
references: Circulation. 1999 Jun 1;99(21):2798-805
references: 10351975
references: Proteomics Clin Appl. 2008 Jun;2(6):845-61
references: 21136884
references: Basic Res Cardiol. 2002 Sep;97(5):409-15
references: 12200641
references: Circ Res. 2006 Sep 29;99(7):706-14
references: 16946135
references: Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H984-99
references: 15563526
references: Circulation. 2002 Nov 26;106(22):2836-41
references: 12451011
references: Circ Res. 1999 Sep 3;85(5):446-56
references: 10473674
references: J Mol Cell Cardiol. 2001 Nov;33(11):1937-44
references: 11708839
references: J Nucl Cardiol. 2005 Jan-Feb;12(1):104-19
references: 15682371
references: Circulation. 1985 Dec;72(6 Pt 2):V123-35
references: 3905053
references: Physiol Rev. 1998 Oct;78(4):1055-85
references: 9790569
references: Eur J Heart Fail. 2007 Apr;9(4):377-83
references: 17127093
references: Prog Cardiovasc Dis. 2001 Mar-Apr;43(5):387-98
references: 11251126
references: J Am Coll Cardiol. 2001 Jun 1;37(7):1989-95
references: 11401143
references: J Proteome Res. 2009 Jun;8(6):2838-50
references: 19290621
references: Circulation. 2004 Nov 23;110(21):3313-21
references: 15545518
references: Circ Res. 2003 Jun 13;92(11):1233-9
references: 12750311
references: Am J Physiol Heart Circ Physiol. 2009 Jul;297(1):H223-32
references: 19395548
references: Circulation. 1999 Dec 7;100(23):2380-6
references: 10587344
references: J Mol Cell Cardiol. 2012 Apr;52(4):822-31
references: 21889943
references: Am J Med. 2010 Nov;123(11):978-86
references: 21035587
references: Circ Res. 2008 Jan 4;102(1):103-12
references: 17967786
references: Circulation. 1997 Apr 1;95(7):1900-9
references: 9107179
references: J Mol Cell Cardiol. 2006 Dec;41(6):980-8
references: 16926020
references: Prog Cardiovasc Dis. 2008 Jul-Aug;51(1):74-88
references: 18634919
references: Circulation. 2001 Dec 11;104(24):2923-31
references: 11739307
references: Circ Res. 2003 Jan 10;92(1):48-55
references: 12522120
references: Cardiovasc Res. 1998 Mar;37(3):606-17
references: 9659444
references: J Thorac Cardiovasc Surg. 2011 Jan;141(1):261-8
references: 21168030
references: Cardiovasc Res. 2002 Dec;56(3):422-32
references: 12445883
references: J Biol Chem. 1979 May 25;254(10):4164-70
references: 571436
references: J Proteome Res. 2008 Jun;7(6):2204-14
references: 18484766
references: Am Heart J. 1989 Jan;117(1):211-21
references: 2783527
references: Am J Physiol. 1999 Oct;277(4):H1418-28
references: 10516177
references: Circ Res. 2002 Nov 15;91(10):970-7
references: 12433843
references: Basic Res Cardiol. 1995 Jan-Feb;90(1):44-6
references: 7779058
references: Circulation. 2000 Aug 22;102(8):908-14
references: 10952961