title: Induction of PGC-1α expression can be detected in blood samples of patients with ST-segment elevation acute myocardial infarction.
abstract: Following acute myocardial infarction (MI), cardiomyocyte survival depends on its mitochondrial oxidative capacity. Cell death is normally followed by activation of the immune system. Peroxisome proliferator activated receptor γ-coactivator 1α (PGC-1α) is a transcriptional coactivator and a master regulator of cardiac oxidative metabolism. PGC-1α is induced by hypoxia and facilitates the recovery of the contractile capacity of the cardiac muscle following an artery ligation procedure. We hypothesized that PGC-1α activity could serve as a good molecular marker of cardiac recovery after a coronary event. The objective of the present study was to monitor the levels of PGC-1α following an ST-segment elevation acute myocardial infarction (STEMI) episode in blood samples of the affected patients. Analysis of blood mononuclear cells from human patients following an STEMI showed that PGC-1α expression was increased and the level of induction correlated with the infarct size. Infarct size was determined by LGE-CMR (late gadolinium enhancement on cardiac magnetic resonance), used to estimate the percentage of necrotic area. Cardiac markers, maximum creatine kinase (CK-MB) and Troponin I (TnI) levels, left ventricular ejection function (LVEF) and regional wall motion abnormalities (RWMA) as determined by echocardiography were also used to monitor cardiac injury. We also found that PGC-1α is present and active in mouse lymphocytes where its expression is induced upon activation and can be detected in the nuclear fraction of blood samples. These results support the notion that induction of PGC-1α expression can be part of the recovery response to an STEMI and could serve as a prognosis factor of cardiac recovery.
authors.affiliation: Servicio de Cardiología, Consorcio Hospital General Universitario de Valencia, Valencia, Spain.
authors.forename: Óscar
authors.initials: Ó
authors.lastname: Fabregat-Andrés
authors.forename: Alberto
authors.initials: A
authors.lastname: Tierrez
authors.forename: Manuel
authors.initials: M
authors.lastname: Mata
authors.forename: Jordi
authors.initials: J
authors.lastname: Estornell-Erill
authors.forename: Francisco
authors.initials: F
authors.lastname: Ridocci-Soriano
authors.forename: María
authors.initials: M
authors.lastname: Monsalve
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D006360:Heat-Shock Proteins / Q000097:blood / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear; D008279:Magnetic Resonance Imaging; D051379:Mice; D009203:Myocardial Infarction / Q000097:blood*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011379:Prognosis; D020127:Recovery of Function; D014157:Transcription Factors / Q000097:blood / Q000235:genetics*; D015533:Transcriptional Activation / Q000502:physiology*
chemical_list: D015415:Biomarkers; D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors
references.citation: Pharmacol Rep. 2009 Jan-Feb;61(1):131-8
references.pmid: 19307701
references.citation: Cell Metab. 2009 Jun;9(6):512-24
references.pmid: 19490906
references.citation: J Mol Med (Berl). 2007 Dec;85(12):1309-15
references.pmid: 18026917
references.citation: J Mol Cell Cardiol. 2008 May;44(5):915-26
references.pmid: 18436235
references.citation: Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):10086-91
references.pmid: 16775082
references.citation: Circ Res. 2004 Sep 17;95(6):568-78
references.pmid: 15375023
references.citation: Rev Esp Cardiol. 2005 Sep;58(9):1062-92
references.pmid: 16185619
references.citation: Rev Esp Cardiol. 2009 Mar;62(3):293, e1-47
references.pmid: 19268074
references.citation: Lancet. 2008 Aug 16;372(9638):570-84
references.pmid: 18707987
references.citation: J Sports Sci. 2009 Jan 1;27(1):49-58
references.pmid: 19031335
references.citation: Circulation. 2001 Nov 20;104(21):2588-94
references.pmid: 11714655
references.citation: Eur Heart J. 2008 May;29(10):1241-9
references.pmid: 17766280
references.citation: Am Heart J. 2008 Dec;156(6):1065-73
references.pmid: 19033000
references.citation: Nat Immunol. 2010 Mar;11(3):265-72
references.pmid: 20139987
references.citation: Annu Rev Physiol. 2006;68:29-49
references.pmid: 16460265
references.citation: Circulation. 2002 Dec 10;106(24):3126-32
references.pmid: 12473562
references.citation: Circ J. 2009 Nov;73(11):2000-8
references.pmid: 19809203
references.citation: Cell Biol Int. 2007 Sep;31(9):1002-9
references.pmid: 17467307
references.citation: Cell Death Differ. 2008 Apr;15(4):621-7
references.pmid: 18259201
references.citation: Int Heart J. 2007 Jul;48(4):533-46
references.pmid: 17827825
references.citation: Diabetologia. 2006 Jul;49(7):1477-88
references.pmid: 16752166
references.citation: Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):12895-900
references.pmid: 20615979
references.citation: Cell. 1999 Jul 9;98(1):115-24
references.pmid: 10412986
references.citation: Diabetes Metab. 2010 Nov;36(5):327-38
references.pmid: 20851652
references.citation: Pharmacol Res. 2010 Apr;61(4):269-80
references.pmid: 19969085
references.citation: J Immunol. 2010 May 1;184(9):4827-41
references.pmid: 20335530
references.citation: Circulation. 2010 Feb 23;121(7):e46-e215
references.pmid: 20019324
references.citation: J Immunol. 2010 Jan 1;184(1):184-90
references.pmid: 19949095
references.citation: Cardiovasc Res. 2005 Jun 1;66(3):562-73
references.pmid: 15914121
references.citation: Clin Exp Pharmacol Physiol. 2002 Apr;29(4):339-45
references.pmid: 11985547
references.citation: Nat Genet. 2003 Jul;34(3):267-73
references.pmid: 12808457
references.citation: J Physiol. 2003 Sep 1;551(Pt 2):491-501
references.pmid: 12824444