title: Sex differences in porcine left ventricular myocardial remodeling due to right ventricular pacing.
abstract: BACKGROUND
  Although sex differences in heart failure (HF) prevalence and severity have been recognized, its molecular mechanisms are poorly understood. We used a tachycardia-induced cardiomyopathy model to determine the sex specific remodeling pattern in male and female adult pigs.
  
  
  METHODS
  We compared the echocardiographic and molecular measures of myocardial remodeling in 19 male and 12 female pigs with chronic symptomatic systolic HF due to right ventricle (RV) pacing (170 bpm) and 6 male and 5 female sham-operated controls. Males achieved subsequent HF stages earlier than females.
  
  
  RESULTS
  The progression of symptomatic HF was associated with the reduction of the left ventricle (LV) ejection fraction in both sexes (all p < 0.05). A significant LV dilatation occurred only in males (p < 0.001). The HF development was accompanied by an increased pro-hypertrophic factor GATA4 and TGF-β1 messenger RNA (mRNA) expression in the LV only in male pigs (all p < 0.01). The total gelatinolytic activity in LV was higher in males than females (irrespective of HF, p < 0.05), and the HF progression was associated with a reduced total gelatinolytic activity (p < 0.05) in the LV only in males. No differences in LV myocardial collagen content were found between HF groups and sexes. Cardiomyocyte cross-sectional diameter was significantly smaller in male hearts as compared to female (p < 0.05).
  
  
  CONCLUSIONS
  Male and female porcine hearts respond differently to RV pacing. Males, most likely due to a higher extracellular matrix turnover, demonstrated a significant LV dilatation, followed by a strong induction of pro-hypertrophic program, and an earlier development of symptomatic HF.
authors.affiliation: Research and Development Centre, Regional Specialist Hospital in Wroclaw, Kamienskiego Street 73a, 51-124 Wroclaw, Poland ; Department of Biochemistry, Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, Norwida Street 31, 50-375 Wroclaw, Poland.
authors.forename: Liliana
authors.initials: L
authors.lastname: Kiczak
authors.affiliation: Research and Development Centre, Regional Specialist Hospital in Wroclaw, Kamienskiego Street 73a, 51-124 Wroclaw, Poland ; Department of Heart Diseases, Wroclaw Medical University, Weigla Street 5, 50-981 Wroclaw, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Tomaszek
authors.affiliation: Research and Development Centre, Regional Specialist Hospital in Wroclaw, Kamienskiego Street 73a, 51-124 Wroclaw, Poland ; Department of Internal Diseases and Clinic of Diseases of Horses, Dogs and Cats, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, Grunwaldzki Sq. 47, 50-366 Wroclaw, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Pasławska
authors.affiliation: Research and Development Centre, Regional Specialist Hospital in Wroclaw, Kamienskiego Street 73a, 51-124 Wroclaw, Poland ; Department of Food Hygiene and Consumer Health Protection, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, Norwida Street 31, 50-375 Wroclaw, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Bania
authors.affiliation: Research and Development Centre, Regional Specialist Hospital in Wroclaw, Kamienskiego Street 73a, 51-124 Wroclaw, Poland ; Department of Internal Diseases and Clinic of Diseases of Horses, Dogs and Cats, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, Grunwaldzki Sq. 47, 50-366 Wroclaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Noszczyk-Nowak
authors.affiliation: Department of Surgery, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, Grunwaldzki Sq. 51, 50-366 Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Skrzypczak
authors.affiliation: Research and Development Centre, Regional Specialist Hospital in Wroclaw, Kamienskiego Street 73a, 51-124 Wroclaw, Poland ; Department and Clinic of Internal and Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, Borowska Street 213, 50-556 Wroclaw, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Pasławski
authors.affiliation: Research and Development Centre, Regional Specialist Hospital in Wroclaw, Kamienskiego Street 73a, 51-124 Wroclaw, Poland ; Department of Biochemistry, Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, Norwida Street 31, 50-375 Wroclaw, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Zacharski
authors.affiliation: Research and Development Centre, Regional Specialist Hospital in Wroclaw, Kamienskiego Street 73a, 51-124 Wroclaw, Poland ; Department of Internal Diseases and Clinic of Diseases of Horses, Dogs and Cats, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, Grunwaldzki Sq. 47, 50-366 Wroclaw, Poland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Janiszewski
authors.affiliation: Department of Animal Physiology and Biostructure, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kuropka
authors.affiliation: Research and Development Centre, Regional Specialist Hospital in Wroclaw, Kamienskiego Street 73a, 51-124 Wroclaw, Poland ; Department of Heart Diseases, Wroclaw Medical University, Weigla Street 5, 50-981 Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
authors.affiliation: Research and Development Centre, Regional Specialist Hospital in Wroclaw, Kamienskiego Street 73a, 51-124 Wroclaw, Poland ; Department of Heart Diseases, Wroclaw Medical University, Weigla Street 5, 50-981 Wroclaw, Poland.
authors.forename: Ewa A
authors.initials: EA
authors.lastname: Jankowska
keywords: Experimental model of heart failure; Extracellular matrix turnover; Myocardial remodeling; Sex