Adiponectin ameliorates endotoxin-induced acute cardiac injury.
Adiponectin ameliorates endotoxin-induced acute cardiac injury.
复制标题
DOI：
10.1155/2014/382035
复制
发表时间：
2014
影响因子：
--
通讯作者：
Komori K
中科院分区：
文献类型：
--
作者：
Watanabe Y;Shibata R;Ouchi N;Kambara T;Ohashi K;Jie L;Inoue Y;Murohara T;Komori K
背景肥胖是心血管疾病的危险因素。越来越多的证据表明，脂肪细胞衍生的血浆蛋白脂联素水平降低与心血管风险增加有关。在此，我们研究了脂联素对脂多糖（LPS）诱导的急性心肌损伤的影响。方法和结果。将单剂量的LPS（10 mg/kg）腹膜内注射到野生型（WT）和脂联素敲除（APN-KO）小鼠中。LPS给药后，与WT小鼠相比，APN-KO小鼠左心室（LV）收缩功能障碍加重。给予WT和APN-KO小鼠LPS导致心脏中炎性细胞因子（包括TNF-α和IL-6）表达增加，但与WT小鼠相比，APN-KO小鼠中这种诱导的幅度更大。脂联素腺病毒载体（Ad-APN）的全身给药改善了脂联素基因敲除小鼠的LPS诱导的左室功能障碍，同时降低了心脏中TNF-α和IL-6的表达。给予依那西普（一种可溶性TNF受体）可消除APN-KO小鼠对LPS反应引起的LV收缩功能降低。结论这些结果表明，脂联素通过抑制心脏炎症反应来保护LPS诱导的急性心脏损伤，并可能成为脓毒症相关心肌功能障碍的潜在治疗靶点。
Background. Obesity is a risk factor for cardiovascular disease. Increasing evidence suggests that reduced levels of the adipocyte-derived plasma protein adiponectin are associated with an increased cardiovascular risk. Here, we examined the effects of adiponectin on lipopolysaccharide- (LPS-) induced acute cardiac injury in vivo. Methods and Results. A single dose of LPS (10 mg/kg) was intraperitoneally injected into wild-type (WT) and adiponectin-knockout (APN-KO) mice. Following LPS administration, APN-KO mice had exacerbation of left ventricular (LV) systolic dysfunction compared with WT mice. Administration of LPS to WT and APN-KO mice led to an increased expression of inflammatory cytokines including TNF-α and IL-6 in the heart, but the magnitude of this induction was greater in APN-KO mice compared to WT mice. Systemic delivery of an adenoviral vector expressing adiponectin (Ad-APN) improved LPS-induced LV dysfunction in APN-KO mice, and this effect was accompanied by the reduced expression of TNF-α and IL-6 in the heart. Administration of etanercept, a soluble TNF receptor abolished the reduced LV contractile function in response to LPS in APN-KO mice. Conclusion. These results suggest that adiponectin protects against LPS-induced acute cardiac injury by suppressing cardiac inflammatory responses, and could represent a potential therapeutic target in sepsis-associated myocardial dysfunction.
登录
查看更多内容
炎症和代谢疾病中的脂肪因子。
DOI：
10.1038/nri2921
发表时间：
2011-02
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
9.6
作者：
El-Solh, A;Sikka, P;Davies, J
通讯作者：
Davies, J
影响因子：
37.8
作者：
Sun, M;Dawood, F;Liu, PP
通讯作者：
Liu, PP
影响因子：
6.9
作者：
Ahima, Rexford S.
通讯作者：
Ahima, Rexford S.
影响因子：
82.9
作者：
Shibata, R;Sato, K;Walsh, K
通讯作者：
Walsh, K