title: Sustained cardiomyocyte apoptosis and left ventricular remodelling after myocardial infarction in experimental diabetes.
abstract: OBJECTIVE
  Diabetes is known to reduce survival after myocardial infarction. Our aim was to examine whether diabetes is associated with enhanced cardiomyocyte apoptosis and thus interferes with the post-infarction remodelling process in myocardium in rat.
  
  
  METHODS
  Four weeks after intravenous streptozotocin (diabetic groups) or citrate buffer (controls) injection, myocardial infarction was produced by ligation of left descending coronary artery. Level of cardiomyocyte apoptosis was quantified by TUNEL and caspase-3 methods. Collagen volume fraction and connective tissue growth factor were determined under microscope. Left ventricular dimensions were evaluated by echocardiography and planimetry.
  
  
  RESULTS
  The number of apoptotic cardiomyocytes was equally high in diabetic and non-diabetic rats after 1 week from infarction. At 12 weeks after infarction the number of apoptotic cells was higher in the diabetic as compared to non-diabetic rats both in the border zone of infarction and in non-infarcted area. Correspondingly, left ventricular end diastolic diameter, relative cardiac weight, connective tissue growth factor-expression and fibrosis were increased in diabetic compared with non-diabetic rats with myocardial infarction.
  
  
  CONCLUSIONS
  Sustained cardiomyocyte apoptosis, left ventricular enlargement, increased cardiac fibrosis and enhanced profibrogenic connective tissue growth factor expression were detected after myocardial infarction in experimental diabetes. Apoptotic myocyte loss could be an important mechanism contributing to progressive dilatation of the heart and poor prognosis after myocardial infarction in diabetes.
authors.affiliation: Department of Medicine, Helsinki University Hospital, HUS, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Bäcklund
authors.forename: E
authors.initials: E
authors.lastname: Palojoki
authors.forename: A
authors.initials: A
authors.lastname: Saraste
authors.forename: A
authors.initials: A
authors.lastname: Eriksson
authors.forename: P
authors.initials: P
authors.lastname: Finckenberg
authors.forename: V
authors.initials: V
authors.lastname: Kytö
authors.forename: P
authors.initials: P
authors.lastname: Lakkisto
authors.forename: E
authors.initials: E
authors.lastname: Mervaala
authors.forename: L-M
authors.initials: LM
authors.lastname: Voipio-Pulkki
authors.forename: M
authors.initials: M
authors.lastname: Laine
authors.forename: I
authors.initials: I
authors.lastname: Tikkanen
mesh_terms: D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000032:analysis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003094:Collagen / Q000032:analysis / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D003331:Coronary Vessels / Q000601:surgery; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D015870:Gene Expression / Q000235:genetics; D006321:Heart / Q000503:physiopathology; D017874:Immediate-Early Proteins / Q000032:analysis / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000378:metabolism; D008026:Ligation; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000473:pathology*; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D001786:Blood Glucose; C526316:CCN2 protein, rat; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D020097:Natriuretic Peptide, Brain; D055513:Connective Tissue Growth Factor; D003094:Collagen; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases