Cardiomyocyte-restricted overexpression of NOS3 limited left ventricular dysfunction and remodeling after myocardial infarction, significantly reducing the LV weight/body weight ratio compared to wild-type mice.
Does cardiomyocyte-specific overexpression of NOS3 improve left ventricular performance and reduce compensatory hypertrophy after myocardial infarction in mice?
Cardiomyocyte-restricted overexpression of NOS3 limits left ventricular dysfunction and remodeling after myocardial infarction in mice, partly by decreasing myocyte hypertrophy.
Absolute Event Rate: 4.6% vs 5.3%
p-value: p=<0.01
Nitric oxide (NO) is an important modulator of cardiac performance and left ventricular (LV) remodeling after myocardial infarction (MI). We tested the effect of cardiomyocyte-restricted overexpression of one NO synthase isoform, NOS3, on LV remodeling after MI in mice. LV structure and function before and after permanent LAD coronary artery ligation were compared in transgenic mice with cardiomyocyte-restricted NOS3 overexpression (NOS3-TG) and their wild-type littermates (WT). Before MI, systemic hemodynamic measurements, echocardiographic assessment of LV fractional shortening (FS), heart weight, and myocyte width (as assessed histologically) did not differ in NOS3-TG and WT mice. The inotropic response to graded doses of isoproterenol was significantly reduced in NOS3-TG mice. One week after LAD ligation, the infarcted fraction of the LV did not differ in WT and NOS3-TG mice (34+/-4% versus 36+/-12%, respectively). Four weeks after MI, however, end-systolic LVID was greater, and fractional shortening and maximum and minimum rates of LV pressure development were less in WT than in NOS3-TG mice. LV weight/body weight ratio was greater in WT than in NOS3-TG mice (5.3+/-0.2 versus 4.6+/-0.5 mg/g; P<0.01). Myocyte width in noninfarcted myocardium was greater in WT than in NOS3-TG mice (18.8+/-2.0 versus 16.6+/-1.6 microm; P<0.05), whereas fibrosis in noninfarcted myocardium was similar in both genotypes. Cardiomyocyte-restricted overexpression of NOS3 limits LV dysfunction and remodeling after MI, in part by decreasing myocyte hypertrophy in noninfarcted myocardium.
Janssens et al. (Tue,) conducted a other in Myocardial Infarction. Cardiomyocyte-restricted overexpression of human NOS3 (NOS3-TG) vs. Wild-type (WT) littermates was evaluated on Left ventricular weight/body weight ratio 4 weeks after myocardial infarction (p=<0.01). Cardiomyocyte-restricted overexpression of NOS3 limited left ventricular dysfunction and remodeling after myocardial infarction, significantly reducing the LV weight/body weight ratio compared to wild-type mice.