Abstract 17285: Adiponectin Regulates Hypertension-Induced Diastolic Heart Failure
Background: Diastolic heart failure (DHF) accounts for ∼50% of heart failure (HF) admissions and is associated with left ventricular hypertrophy (LVH), myocardial fibrosis and cardiac inflammation. Hypertension is a major cause of DHF. Adiponectin (APN) an adipokine, exerts anti-inflammatory and anti-hypertrophic effects. Hypoadiponectinemia is implicated in development and progression of hypertension-induced DHF. We tested the hypothesis that chronic APN overexpression ameliorates the progression from HTN to DHF.
Methods: Male C57BL/6J (WT) and APN transgenic (APNtg) mice underwent sham surgery (n=7) or uninephrectomy, aldosterone-infusion and fed 1% salt water for 4-weeks (ALDO) (n=8). After 4-weeks tail-cuff blood pressure (BP), echocardiogram and gene analyses by RT-PCR were performed.
Results: BP was increased in WT-ALDO mice vs. WT-sham (137±4 vs. 107±5mmHg; p<0.01) and was partially abrogated in APNtg-ALDO mice (128±3mmHg; p<0.05 vs. WT-ALDO). APNtg-sham mice were normotensive (102±3mmHg). LVH was increased in WT-ALDO vs. WT-sham mice (HW/BW ratio: 5.2±0.2 vs. 4.4±0.2mg/g; p<0.05). LVH was decreased in APNtg-ALDO mice (HW/BW ratio: 4.8±0.2; p=NS vs. WT-ALDO). APNtg-sham mice had no LVH. Total wall thickness was decreased in APNtg-ALDO mice (1.07±0.02 vs.1.27±0.02mm; p<0.05 vs. WT-ALDO). LV end-diastolic and end-systolic diameters were no different between WT-ALDO and APNtg-ALDO hearts. Similarly LVEF was unchanged between WT-ALDO and APNtg-ALDO hearts (54±1% vs. 54±0.5%). In WT-ALDO hearts LVH was associated with a ∼9-fold increase in ANF expression vs. <2-fold increase in APNtg-ALDO hearts. TGFβ was increased ∼2.4 fold in WT-ALDO hearts vs. 0.6 fold in APNtg-ALDO hearts. This was accompanied by an increase in collagen-I and collagen-III expression (8.4 vs. 1.1-fold and 5.4 vs. 1.2-fold respectively) in WT-ALDO vs. APNtg-ALDO hearts.
Conclusions: APNtg-sham mice had no cardiac phenotype. APNtg mice showed a reduction in BP and LVH only under conditions of chronic ALDO infusion. These data demonstrate that chronic APN overexpression modulates hypertension, LVH and a reduction in cardiac collagen. Our findings suggest that APN may represent a therapeutic target for hypertension-induced DHF.
- © 2010 by American Heart Association, Inc.