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Background Heart failure (HF) is characterized by inflammation, insulin resistance and progressive catabolism. We hypothesized that patients with advanced HF also develop adipose tissue inflammation associated with impaired adipokine signaling and that hemodynamic correction through implantation of ventricular assist devices (VADs) would reverse adipocyte activation and correct adipokine signaling in advanced HF. Methods and Results Circulating insulin, adiponectin, leptin and resistin levels were measured in 36 patients with advanced HF before and after VAD implantation and 10 healthy controls. Serum adiponectin was higher in HF patients pre-VAD compared to controls (13.3±4.9 vs. 6.4±2.1 μg/ml, p=0.02). VAD implantation (mean 129±99 days) reduced serum adiponectin (7.4±3.4 μg/ml, p<0.05) and improved insulin resistance (Homeostasis Assessment Model of insulin resistance: 6.3±5.8 to 3.6±2.9; p<0.05). Adiponectin expression in adipose tissue decreased after VAD implantation (−65%; p<0.03). Adiponectin receptor expression was suppressed in the failing myocardium compared to controls and increased after mechanical unloading. Histomorphometric analysis of adipose tissue specimens revealed reduced adipocyte size in patients with advanced HF compared to controls (1999±24 μm2 vs. 5583±142 μm2 in controls; p<0.05), which increased after VAD placement. Of note, macrophage infiltration in adipose tissue was higher in advanced HF patients compared to controls (+25%; p<0.01), which normalized after VAD implantation. Conclusions Adipose tissue inflammation and adiponectin resistance develop in advanced HF. Mechanical unloading of the failing myocardium reverses adipose tissue macrophage infiltration, inflammation and adiponectin resistance in patients with advanced HF.

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Adaptation to extra-uterine life and postnatal remodelling of intra-acinar arteries was followed in 34 Large White pigs, from birth to adult life, applying morphometry to light and electronmicroscopic studies. After birth, percentage wall thickness decreased rapidly due to a reduction in overlap of adjacent smooth muscle cells and an increase in smooth muscle cell surface area/volume ratio, (p less than 0.01 at 12 h), without a reduction in the volume density of smooth muscle cells. Smooth muscle cells appeared immature at birth and synthetic rather than contractile organelles predominated. Between 3 weeks and 6 months myofilament volume density doubled (p less than 0.0001). At all ages, pericytes, intermediate and smooth muscle cells showed similar volume densities of contractile and synthetic organelles. Thus, the high fetal pulmonary vascular resistance appeared to be due to the shape and arrangement of smooth muscle and other contractile cells within the vessel wall, rather than an excessive contractility of these cells. After birth rapid remodelling of arterial wall structure achieved a reduction in wall thickness by 30 min, continuing during the first week of life. After 3 weeks, remodelling involved an increase in wall thickness, connective tissue deposition with more collagen than elastin (p less than 0.0001), and smooth muscle cell differentiation.

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