Abstract 1261: Adiponectin Regulates Aldosterone-Induced Hypertension and Hypertrophy in Diastolic Heart Failure
Background: Diastolic heart failure (DHF) accounts for ~40% of HF admissions and is associated with cardiac fibrosis, left ventricular hypertrophy (LVH) and inflammation. Adiponectin (APN) is an adipose-derived plasma protein, which exerts anti-inflammatory and anti-hypertrophic effects. Hypoadiponectinemia is implicated in development of salt-induced hypertension (HTN). We tested the hypothesis that APN may mediate the progression from HTN and LVH to DHF.
Methods: 12-week old male C57BL/6J (WT) or APN deficient (APNKO) mice underwent either sham surgery (n=8) or uninephrectomy, aldosterone-infusion and fed 1% salt water for 4-weeks (ALDO) (n=8). 4-weeks after surgery, tail-cuff blood pressure (BP), echocardiogram and protein analyses were performed.
Results: BP was increased in WT-ALDO mice vs. WT-sham (132±2 vs. 109±3mmHg; p<0.001) and was further elevated in APNKO ALDO mice (140±3mmHg; p<0.05 vs. WT-ALDO). LVH was increased in WT-ALDO vs. WT-sham mice (HW/BW ratio: 4.4±0.1 vs. 4.1±0.1mg/g; p<0.05). However, LVH in APNKO ALDO mice was further exacerbated (HW/BW ratio: 6.5±0.9 vs. 4.4±0.1mg/g; p<0.05 vs. WT-ALDO). Increases in both LV end diastolic and LV end systolic dimensions were caused by ALDO but were no different from ALDO-treated APNKO hearts (3.8±1.2 vs. 1.5±0.2, and 3.5±0.1 vs. 1.15±0.1mm, respectively). Similarly LV EF was unchanged in APNKO ALDO and WT-ALDO hearts (62±2% vs. 63±1%). Additionally there was more pulmonary congestion, as measured by wet/dry lung ratio in ALDO APNKO mice (p<0.05 vs. WT-ALDO). LVH was associated with a ~3-fold increase in MMP2/TIMP2 ratio in WT-ALDO hearts (p<0.05 vs. WT-sham). Intriguingly, compared to WT-ALDO mice, APNKO had no increase in MMP2/TIMP2 ratio (p<0.05), despite having more LVH. Cardiac protein expression of INF-γ, IL-1β, TNF-α was increased in all ALDO-treated mice vs. appropriate sham, however only INF-γ was markedly increased (~4-fold; p<0.001) in APNKO vs. WT-ALDO hearts.
Conclusions. Thus, these data demonstrate that APN-deficiency contributes to hypertension and hypertrophy. Additionally, in this model of HTN and diastolic dysfunction there is increased inflammation. Our findings suggest that APN may represent a novel target for hypertensive heart disease and DHF.