title: Reduction in myocardial collagen cross-linking parallels left ventricular dilatation in rat models of systolic chamber dysfunction.
abstract: BACKGROUND
  The transition from compensated left ventricular hypertrophy (LVH) to heart failure is associated with alterations in the myocardial interstitium. We hypothesized that LV dilatation is associated with modifications in collagen cross-linking.
  
  
  RESULTS
  We studied 2 rat models of LV dilatation: (1) pressure-overload hypertrophy with heart failure (POH-F) induced by suprarenal abdominal aortic banding and (2) LVH induced by 7 months of isoproterenol (ISO, 0.04 mg x kg(-1) x d(-1)) administration. In POH-F rats and in rats receiving ISO, LV dilatation and a reduced systolic chamber performance were noted. Myocardial hydroxyproline concentrations ([HPRO]) were increased in the POH-F rats, whereas in rats receiving ISO, [HPRO] was decreased. In POH-F rats, the ratio of myocardial collagen type I to type III was increased, but in rats receiving ISO, myocardial collagen I/III was unchanged. In contrast to the diverse changes in myocardial collagen concentrations and phenotypes observed in the 2 models of LV dilatation, the ratio of myocardial insoluble to soluble (relationship between cross-linked and non-cross-linked) collagen was decreased in both the POH-F and ISO groups. Moreover, administration of captopril (0.22 mmol x kg(-1) x d(-1)), which inhibited the ISO-induced reduction in myocardial insoluble/soluble collagen but not the reduction in [HPRO], prevented the ISO-induced alterations in LV dimensions and performance.
  
  
  CONCLUSIONS
  Because decreases in the ratio of myocardial insoluble to soluble collagen parallel LV dilatation in rats, reductions in myocardial collagen cross-linking may be an important mechanism contributing to LV dilatation in heart disease.
authors.affiliation: Laboratory of Cardiovascular Pathophysiology, Department of Physiology, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: A J
authors.initials: AJ
authors.lastname: Woodiwiss
authors.forename: O J
authors.initials: OJ
authors.lastname: Tsotetsi
authors.forename: S
authors.initials: S
authors.lastname: Sprott
authors.forename: E J
authors.initials: EJ
authors.lastname: Lancaster
authors.forename: T
authors.initials: T
authors.lastname: Mela
authors.forename: E S
authors.initials: ES
authors.lastname: Chung
authors.forename: T E
authors.initials: TE
authors.lastname: Meyer
authors.forename: G R
authors.initials: GR
authors.lastname: Norton
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D001012:Aorta, Abdominal / Q000503:physiopathology / Q000601:surgery; D001835:Body Weight / Q000187:drug effects; D002216:Captopril / Q000627:therapeutic use; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D003251:Constriction, Pathologic; D004195:Disease Models, Animal; D004452:Echocardiography; D006909:Hydroxyproline / Q000378:metabolism; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D066298:In Vitro Techniques; D007545:Isoproterenol; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis; D013599:Systole / Q000187:drug effects*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy*; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D003094:Collagen; D002216:Captopril; D007545:Isoproterenol; D006909:Hydroxyproline