title: Gender-specific patterns of left ventricular and myocyte remodeling following myocardial infarction in mice deficient in the angiotensin II type 1a receptor.
abstract: Left ventricular (LV) remodeling after myocardial infarction (MI) results from hypertrophy of myocytes and activation of fibroblasts induced, in part, by ligand stimulation of the ANG II type 1 receptor (AT1R). The purpose of the present study was to explore the specific role for activation of the AT 1a R subtype in post-MI remodeling and whether gender differences exist in the patterns of remodeling in wild-type and AT 1a R knockout (KO) mice. AT 1a R-KO mice and wild-type littermates underwent coronary ligation to induce MI or sham procedures; echocardiography and hemodynamic evaluation were performed 6 wk later, and LV tissue was harvested for infarct size determination, morphometric measurements, and gene expression analysis. Survival and infarct size were similar among all male and female wild-type and AT 1a R-KO mice. Hemodynamic indexes were also similar except for lower systolic blood pressure in the AT 1a R-KO mice compared with wild-type mice. Male and female wild-type and male AT 1a R-KO mice developed similar increases in LV chamber size, LV mass corrected for body weight (LV/BW), and myocyte cross-sectional area (CSA). However, female AT 1a R-KO mice demonstrated no increase in LV/BW and myocyte CSA post-MI compared with shams. Both male and female wild-type mice demonstrated higher atrial natriuretic peptide (ANP) levels after MI, with female wild types being significantly greater than males. However, male and female AT 1a R-KO mice developed no increase in ANP gene expression with MI despite an increase in LV mass and myocyte size in males. These data support that gender-specific patterns of LV and myocyte hypertrophy exist after MI in mice with a disrupted AT 1a R gene, and suggest that myocyte hypertrophy post-MI in females relies, in part, on activation of the AT 1a R. Further work is necessary to explore the potential mechanisms underlying these gender-based differences.
authors.affiliation: Molecular Cardiology Research Institute, Tufts-New England Medical Center, Box 80, 750 Washington St., Boston, MA 02111, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Bridgman
authors.forename: Mark A
authors.initials: MA
authors.lastname: Aronovitz
authors.forename: Rahul
authors.initials: R
authors.lastname: Kakkar
authors.forename: Michael I
authors.initials: MI
authors.lastname: Oliverio
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Coffman
authors.forename: William M
authors.initials: WM
authors.lastname: Rand
authors.forename: Marvin A
authors.initials: MA
authors.lastname: Konstam
authors.forename: Michael E
authors.initials: ME
authors.lastname: Mendelsohn
authors.forename: Richard D
authors.initials: RD
authors.lastname: Patten
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D003094:Collagen / Q000378:metabolism; D024042:Collagen Type I / Q000235:genetics; D004452:Echocardiography; D005260:Female; D015870:Gene Expression; D006439:Hemodynamics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000473:pathology; D044140:Receptor, Angiotensin, Type 1 / Q000172:deficiency*; D011945:Receptors, Angiotensin / Q000235:genetics; D012737:Sex Factors; D016019:Survival Analysis; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D024042:Collagen Type I; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D009320:Atrial Natriuretic Factor; D003094:Collagen