Obesity promotes inflammation in periaortic adipose tissue and angiotensin II-induced abdominal aortic aneurysm formation.
Obesity promotes inflammation in periaortic adipose tissue and angiotensin II-induced abdominal aortic aneurysm formation.
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DOI：
10.1161/atvbaha.109.192658
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发表时间：
2009-10
期刊：
影响因子：
--
通讯作者：
Cassis LA
中科院分区：
文献类型：
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作者：
Police SB;Thatcher SE;Charnigo R;Daugherty A;Cassis LA
肥胖促进巨噬细胞向脂肪组织浸润，并与几种心血管疾病的增加有关。向小鼠输注血管紧张素II （AngII）可诱导腹腔主动脉瘤（AAAs）形成，并伴有巨噬细胞深度内、外浸润。我们试图确定肥胖是否会促进腹主动脉周围脂肪组织中的巨噬细胞浸润和促炎细胞因子，并增加血管i诱导的AAAs。肥胖小鼠腹主动脉周围为肥大的白色脂肪细胞，胸主动脉周围为棕色脂肪细胞。腹腔巨噬细胞促炎趋化因子及其受体mRNA丰度与胸主动脉周围脂肪组织相比，肥胖在更大程度上升高。肥胖小鼠腹主动脉周围脂肪组织外植体比胸主动脉外植体释放出更高浓度的MCP-1，促进巨噬细胞迁移。雄性C57BL/6小鼠分别饲喂高脂（HF）饲粮1、2、4个月，然后注射AngII (1000 ng/kg/min) 28天。随着HF喂养时间的延长，AAA发生率逐渐增加（分别为18%、36%和60%）。同样，与瘦对照组相比，血管灌注ob/ob小鼠的AAAs增加（分别为76%和32%，P<0.05）。向肥胖小鼠输注AngII可促进巨噬细胞进一步向主动脉周围和内脏脂肪组织浸润，出现AAAs的肥胖小鼠内脏脂肪组织中的巨噬细胞含量高于未发生AAAs的小鼠。血管灌注肥胖小鼠腹主动脉周围脂肪组织巨噬细胞积累增加与AAA形成增强有关。
Obesity promotes macrophage infiltration into adipose tissue and is associated with increases in several cardiovascular diseases. Infusion of angiotensin II (AngII) to mice induces formation of abdominal aortic aneurysms (AAAs) with profound medial and adventitial macrophage infiltration. We sought to determine if obesity promotes macrophage infiltration and proinflammatory cytokines in periaortic adipose tissue surrounding abdominal aortas and increases AngII-induced AAAs. Hypertrophied white adipocytes surrounded abdominal aortas while brown adipocytes surrounded thoracic aortas of obese mice. mRNA abundance of macrophage proinflammatory chemokines and their receptors were elevated with obesity to a greater extent in abdominal compared to thoracic periaortic adipose tissue. Periaortic adipose tissue explants surrounding abdominal aortas of obese mice released greater concentrations of MCP-1 and promoted more macrophage migration than explants from thoracic aortas. Male C57BL/6 mice were fed a high fat (HF) diet for 1, 2, or 4 months and then infused with AngII (1,000 ng/kg/min) for 28 days. AAA incidence increased progressively with the duration of HF feeding (18%, 36% and 60%, respectively). Similarly, AngII-infused ob/ob mice exhibited increased AAAs compared to lean controls (76% compared to 32%, respectively, P<0.05). Infusion of AngII to obese mice promoted further macrophage infiltration into periaortic and visceral adipose tissue, and obese mice exhibiting AAAs had greater macrophage content in visceral adipose tissue than mice not developing AAAs. Increased macrophage accumulation in periaortic adipose tissue surrounding abdominal aortas of AngII-infused obese mice is associated with enhanced AAA formation.