Division of Preventive Medicine and Nutrition, Columbia University Medical Center, New York, NY 10032, USA.
Circ Heart Fail. 2012 May 1;5(3):340-8. doi: 10.1161/CIRCHEARTFAILURE.111.964031. Epub 2012 Feb 29.
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.
Circulating insulin, adiponectin, leptin, and resistin levels were measured in 36 patients with advanced HF before and after VAD implantation and 10 healthy control subjects. Serum adiponectin was higher in HF patients before VAD implantation compared with control subjects (13.3±4.9 versus 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: 7.6±7.7-4.5±3.6; P=0.012). [corrected] Adiponectin expression in adipose tissue decreased after VAD implantation (-65%; P<0.03). Adiponectin receptor expression was suppressed in the failing myocardium compared with control subjects and increased after mechanical unloading. Histomorphometric analysis of adipose tissue specimens revealed reduced adipocyte size in patients with advanced HF compared with control subjects (2105±585 μm(2) [corrected] versus 5583±142 μm(2) in control subjects; P<0.05), which increased after VAD placement. Of note, macrophage infiltration in adipose tissue was higher in advanced HF patients compared with control subjects (+25%; P<0.01), which normalized after VAD implantation.
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.
心力衰竭（HF）的特征为炎症、胰岛素抵抗和进行性分解代谢。我们假设，晚期 HF 患者还会出现与脂联素信号受损相关的脂肪组织炎症，并且通过植入心室辅助装置（VAD）纠正血液动力学可以逆转晚期 HF 中的脂肪细胞激活并纠正脂联素信号。
在 VAD 植入前后，我们测量了 36 例晚期 HF 患者和 10 例健康对照者的循环胰岛素、脂联素、瘦素和抵抗素水平。与对照组相比，VAD 植入前 HF 患者的血清脂联素水平更高（13.3±4.9 与 6.4±2.1 μg/mL，P=0.02）。VAD 植入（平均 129±99 天）降低了血清脂联素（7.4±3.4 μg/mL，P<0.05）并改善了胰岛素抵抗（稳态模型评估的胰岛素抵抗：7.6±7.7-4.5±3.6；P=0.012）。VAD 植入后，脂肪组织中的脂联素表达减少（-65%；P<0.03）。与对照组相比，衰竭心肌中的脂联素受体表达受到抑制，而在机械卸载后增加。对脂肪组织标本的组织形态计量学分析显示，与对照组相比，晚期 HF 患者的脂肪细胞体积减小（2105±585 μm(2) [校正]与对照组中的 5583±142 μm(2)；P<0.05），而 VAD 放置后则增加。值得注意的是，与对照组相比，晚期 HF 患者的脂肪组织中巨噬细胞浸润更高（+25%；P<0.01），而 VAD 植入后则恢复正常。
晚期 HF 中会出现脂肪组织炎症和脂联素抵抗。衰竭心肌的机械卸载可逆转晚期 HF 患者的脂肪组织巨噬细胞浸润、炎症和脂联素抵抗。
