Immune-inflammatory dysregulation modulates the incidence of progressive fibrosis and diastolic stiffness in the aging heart.
Immune-inflammatory dysregulation modulates the incidence of progressive fibrosis and diastolic stiffness in the aging heart.
复制标题
DOI：
10.1016/j.yjmcc.2010.10.019
复制
发表时间：
2011-01
影响因子：
5
通讯作者：
Entman ML
中科院分区：
文献类型：
--
作者：
Cieslik KA;Taffet GE;Carlson S;Hermosillo J;Trial J;Entman ML
心脏老化的舒张功能障碍是一种严重的疾病，它挑战着越来越多的人的生活和生活方式。本报告旨在探讨炎症失调在衰老小鼠间质性心肌纤维化和进行性舒张功能障碍中的作用和相互关系。我们研究了一群在30个月以上出现进行性舒张功能障碍的C57BL/6小鼠。这种进行性功能障碍与骨髓来源的CD45+成纤维细胞浸润增加有关。此外，通过细胞前胶原蛋白测量，胶原蛋白表达率的增加在心脏中作为年龄的函数很明显。这些细胞和功能变化与MCP-1和IL-13 mRNA的进行性增加有关，这在时间和数量上与纤维化和细胞前胶原水平的变化相关。MCP-1蛋白也增加，主要存在于静脉内皮。蛋白质分析也显示IL-4和IL-13的升高，这表明衰老的心脏向Th2表型转移。体外研究表明，IL-13显著促进单核细胞成纤维细胞转化。我们的研究结果表明，衰老心脏中的免疫炎症失调诱导了MCP-1的产生，并增加了向Th2表型的转变，同时心肌间质纤维化、细胞胶原合成和含有前胶原的CD45+髓源性成纤维细胞数量的增加也随之增加。时间关联和功能相关性提示年龄依赖性免疫炎症功能障碍、纤维化和舒张功能障碍之间存在因果关系。
Diastolic dysfunction in the aging heart is a grave condition that challenges the life and lifestyle of a growing segment of our population. This report seeks to examine the role and interrelationship of inflammatory dysregulation in interstitial myocardial fibrosis and progressive diastolic dysfunction in aging mice. We studied a population of C57BL/6 mice that developed progressive diastolic dysfunction over 30 months of life. This progressive dysfunction was associated with increasing infiltration of CD45+ fibroblasts of myeloid origin. In addition, increased rates of collagen expression as measured by cellular procollagen were apparent in the heart as a function of age. These cellular and functional changes were associated with progressive increases in mRNA for MCP-1 and IL-13 which correlated both temporally and quantitatively with changes in fibrosis and cellular procollagen levels. MCP-1 protein was also increased and found to be primarily in the venular endothelium. Protein assays also demonstrated elevation of IL-4 and IL-13 suggesting a shift to a Th2 phenotype in the aging heart. In vitro studies demonstrated that IL-13 markedly enhanced monocyte fibroblast transformation. Our results indicate that immunoinflammatory dysregulation in the aging heart induces progressive MCP-1 production and an increased shift to a Th2 phenotype paralleled by an associated increase in myocardial interstitial fibrosis, cellular collagen synthesis, and increased numbers of CD45+ myeloid-derived fibroblasts that contain procollagen. The temporal association and functional correlations suggests a causative relationship between age-dependent immunoinflammatory dysfunction, fibrosis and diastolic dysfunction.
登录
查看更多内容
影响因子：
5
作者：
Brooks, WW;Conrad, CH
通讯作者：
Conrad, CH
DOI：
10.1152/ajpheart.00206.2001
发表时间：
2002-02-01
影响因子：
4.8
作者：
Gould, KE;Taffet, GE;Entman, ML
通讯作者：
Entman, ML
影响因子：
--
作者：
Basso, N;Paglia, N;Inserra, F
通讯作者：
Inserra, F
DOI：
10.1152/ajpheart.00393.2007
发表时间：
2007-09-01
影响因子：
4.8
作者：
Basso, Nidia;Cini, Rosa;Inserra, Felipe
通讯作者：
Inserra, Felipe
影响因子：
8.3
作者：
INSERRA, F;ROMANO, L;FERDER, L
通讯作者：
FERDER, L