title: Angiotensin AT2 receptor deficiency after myocardial infarction: its effects on cardiac function and fibrosis depend on the stimulus.
abstract: Hearts of normotensive angiotensin II type 2 receptor (AT2)-deficient mice do not develop fibrosis after angiotensin II-induced chronic hypertension. Thus, the goal of our study was to clarify whether AT2 knockouts (KOs) are also characterized by altered left ventricular (LV) function and modified remodeling of the extracellular matrix (ECM) after induction of myocardial infarction (MI). MI was induced in 5-mo-old female AT2-deficient mice and controls by occlusion of the left coronary artery. Time-matched sham-operated animals served as controls. After 48 h, the first sets of mice were hemodynamically characterized using a pressure-tip catheter (n = 8/group). We also obtained pressure volume loops using a microconductance catheter in additional sets of animals 3 wk after induction of MI (n = 7/group). Finally, the collagen index was illustrated by Sirius red staining and quantified by digital analysis. Whereas the LV function of sham-operated animals did not differ between both genotypes, the collagen index was 44% lower in KO animals. Forty-eight hours and 3 wk post-MI, systolic and diastolic LV function were impaired in both AT2-deficient and wild-type (WT) animals to the same extent by approx 45%. No differences were found between the two genotypes with respect to LV hypertrophy and the fibrosis index in the infarcted and noninfarcted areas 3 wk post-MI. While AT2-KO mice had less cardiac collagen content under basal conditions, the receptor deficiency had no significant influence on LV function at the two investigated time points after induction of MI or on the remodeling of ECM at the latter time point. Thus, hypertension-induced fibrosis is probably triggered by other control mechanisms than fibrosis induced by MI.
authors.affiliation: Department of Cardiology, Charité Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Tschöpe
authors.forename: Dirk
authors.initials: D
authors.lastname: Westermann
authors.forename: Nasser
authors.initials: N
authors.lastname: Dhayat
authors.forename: Sameer
authors.initials: S
authors.lastname: Dhayat
authors.forename: Christine
authors.initials: C
authors.lastname: Altmann
authors.forename: Paul
authors.initials: P
authors.lastname: Steendijk
authors.forename: Heinz-Peter
authors.initials: HP
authors.lastname: Schultheiss
authors.forename: Thomas
authors.initials: T
authors.lastname: Walther
mesh_terms: D000818:Animals; D004719:Endomyocardial Fibrosis / Q000209:etiology / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000150:complications / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000172:deficiency*; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000378:metabolism*; D020257:Ventricular Remodeling
chemical_list: D044139:Receptor, Angiotensin, Type 2