Shibata Rei, Ouchi Noriyuki, Kihara Shinji, Sato Kaori, Funahashi Tohru, Walsh Kenneth
Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street W611, Boston, Massachusetts 02118 , USA.
J Biol Chem. 2004 Jul 2;279(27):28670-4. doi: 10.1074/jbc.M402558200. Epub 2004 Apr 28.
Obesity is a risk factor for the development of cardiovascular diseases that are associated with impaired angiogenesis. Adiponectin is an adipocyte-specific adipocytokine with anti-atherogenic and anti-diabetic properties, and its plasma levels are reduced in association with obesity-linked diseases. Here, we investigated whether adiponectin regulates angiogenesis in response to tissue ischemia using adiponectin knock-out (KO) mice. Angiogenic repair of ischemic hind limbs was impaired in adiponectin-KO mice compared with wild-type (WT) mice as evaluated by laser Doppler flow method and capillary density analyses. Adenovirus-mediated supplement of adiponectin accelerated angiogenic repair in both adiponectin-KO and WT mice. Intramuscular injection of an adenovirus encoding dominant-negative AMP-activated kinase diminished the improvement in limb perfusion seen in WT mice and abolished the adiponectin-induced enhancement of perfusion. These data indicate that adiponectin can function to stimulate angiogenesis in response to ischemic stress by promoting AMP-activated kinase signaling. Therefore, adiponectin may be useful in the treatment for obesity-related vascular deficiency diseases.
肥胖是与血管生成受损相关的心血管疾病发生的一个风险因素。脂联素是一种具有抗动脉粥样硬化和抗糖尿病特性的脂肪细胞特异性脂肪因子，其血浆水平在与肥胖相关的疾病中会降低。在此，我们使用脂联素基因敲除（KO）小鼠研究了脂联素是否响应组织缺血而调节血管生成。通过激光多普勒血流法和毛细血管密度分析评估，与野生型（WT）小鼠相比，脂联素-KO小鼠缺血后肢的血管生成修复受损。腺病毒介导的脂联素补充加速了脂联素-KO和WT小鼠的血管生成修复。肌肉注射编码显性负性AMP激活蛋白激酶的腺病毒减少了WT小鼠肢体灌注的改善，并消除了脂联素诱导的灌注增强。这些数据表明，脂联素可通过促进AMP激活蛋白激酶信号传导来响应缺血应激刺激血管生成。因此，脂联素可能对肥胖相关的血管缺陷疾病治疗有用。
