Increased Age-Related Cardiac Dysfunction in Bradykinin B2 Receptor-Deficient Mice
Increased Age-Related Cardiac Dysfunction in Bradykinin B2 Receptor-Deficient Mice
复制标题
缓激肽 B2 受体缺陷小鼠中与年龄相关的心脏功能障碍增加
DOI：
10.1093/gerona/glu210
复制
发表时间：
2016-02-01
影响因子：
5.1
通讯作者：
Tu, Ling
中科院分区：
文献类型：
--
作者：
Feng, Wenjing;Xu, Xizhen;Tu, Ling
实验证据表明，激肽肽与缓激肽B2受体（B2 R）结合，对心血管系统产生多种有益作用。然而，B2 R在心脏衰老中的作用和潜在机制仍不清楚。在C57 BL/6 J小鼠中观察到心肌中B2 R表达的显著年龄依赖性降低。超声心动图测量显示，衰老引起C57 BL/6 J小鼠的显著心功能障碍，重要的是B2 R缺乏加重了衰老小鼠的这种功能障碍。衰老心脏中B2 R表达的缺乏抑制了p53-pGC-1a诱导的线粒体更新，增加了活性氧的产生，并破坏了线粒体超微结构。B2 R的减少或缺乏增加了氧化应激、巨噬细胞浸润和炎性细胞因子表达，并损害了抗氧化酶的表达。此外，炎症信号主要通过p38 MAPK、JNK的激活以及随后的核因子-κ B向核的移位来介导。总之，我们的数据提供的证据表明，B2 R缺乏有助于衰老诱导的心功能障碍，这可能是由线粒体功能障碍，氧化应激和炎症增加介导的。这项研究表明，防止心脏保护性B2 R表达的丧失可能是预防和治疗年龄相关性心功能不全的新方法。
Experimental evidence indicates that the kinin peptide binds to bradykinin B2 receptor (B2R) to trigger various beneficial effects on the cardiovascular system. However, the effects and underlying mechanisms of B2R in cardiac aging remain unknown. A significant age-dependent decrease in B2R expression in the myocardium was observed in C57BL/6J mice. Echocardiographic measurements showed that aging caused a significant cardiac dysfunction in C57BL/6J mice, and importantly B2R deficiency augmented this dysfunction in aging mice. The deficiency of B2R expression in the aging heart repressed p53-pGC-1a-induced mitochondria renewal, increased reactive oxygen species production, and destroyed mitochondrial ultrastructure. Age-related decrease or lack of B2R increased oxidative stress, macrophage infiltration, and inflammatory cytokine expression and compromised antioxidant enzyme expression. Moreover, the inflammatory signals were mainly mediated by the activation of p38 MAPK, JNK, and subsequent translocation of nuclear factor-kappa B to the nucleus. In summary, our data provide evidence that B2R deficiency contributes to the aging-induced cardiac dysfunction, which is likely mediated by increased mitochondrial dysfunction, oxidative stress, and inflammation. This study indicates that preventing the loss of cardioprotective B2R expression may be a novel approach for the prevention and treatment of age-related cardiac dysfunction.