Mononuclear Phagocytes Are Dispensable for Cardiac Remodeling in Established Pressure-Overload Heart Failure.
Mononuclear Phagocytes Are Dispensable for Cardiac Remodeling in Established Pressure-Overload Heart Failure.
复制标题
单核吞噬细胞在已建立的压力超负荷心力衰竭中可用于心脏重塑。
DOI：
10.1371/journal.pone.0170781
复制
发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Prabhu SD
中科院分区：
文献类型：
--
作者：
Patel B;Ismahil MA;Hamid T;Bansal SS;Prabhu SD
虽然心脏和脾脏单核吞噬细胞（MP），即，单核细胞、巨噬细胞和树突状细胞（DC）是心肌梗死后心脏重构的关键因素，但它们在压力超负荷重构中的作用尚不清楚。我们测试了这样的假设，即这些免疫细胞是压力超负荷心力衰竭（HF）重塑进展所必需的，MP耗竭将改善重塑。对C57 BL/6小鼠进行横向主动脉缩窄（TAC）或假手术，并评估MP的变化。与假手术组相比，TAC小鼠在压力超负荷后早期（1周），在显著肥大和收缩功能障碍之前，循环LyC 6 hi单核细胞和促炎性CD 206 −心脏巨噬细胞扩增，随后在慢性HF期间消退。相比之下，经典的DC在心脏中以双相方式扩增，在建立的HF期间，早期（类似于巨噬细胞）和晚期（8周）都有峰值。脾脏中循环DC或Ly 6C+单核细胞和DC没有显著扩增。在巨噬细胞Fas诱导的凋亡（MaFIA）转基因小鼠中，TAC后2至16周的周期性全身MP耗竭并没有改变心脏重塑进展，TAC后建立HF的小鼠脾切除术也没有改变。最后，将TAC HF小鼠的脾细胞过继转移到未处理的受体中不会诱导受体小鼠的立即或长期心功能障碍。压力超负荷时，单核巨噬细胞群体在心脏中以阶段性方式扩张。然而，一旦明显的肥大和血单核细胞增多正常化，它们就被认为是重塑和衰竭的进展。
Although cardiac and splenic mononuclear phagocytes (MPs), i.e., monocytes, macrophages and dendritic cells (DCs), are key contributors to cardiac remodeling after myocardial infarction, their role in pressure-overload remodeling is unclear. We tested the hypothesis that these immune cells are required for the progression of remodeling in pressure-overload heart failure (HF), and that MP depletion would ameliorate remodeling. C57BL/6 mice were subjected to transverse aortic constriction (TAC) or sham operation, and assessed for alterations in MPs. As compared with sham, TAC mice exhibited expansion of circulating LyC6hi monocytes and pro-inflammatory CD206− cardiac macrophages early (1 w) after pressure-overload, prior to significant hypertrophy and systolic dysfunction, with subsequent resolution during chronic HF. In contrast, classical DCs were expanded in the heart in a biphasic manner, with peaks both early, analogous to macrophages, and late (8 w), during established HF. There was no significant expansion of circulating DCs, or Ly6C+ monocytes and DCs in the spleen. Periodic systemic MP depletion from 2 to 16 w after TAC in macrophage Fas-induced apoptosis (MaFIA) transgenic mice did not alter cardiac remodeling progression, nor did splenectomy in mice with established HF after TAC. Lastly, adoptive transfer of splenocytes from TAC HF mice into naïve recipients did not induce immediate or long-term cardiac dysfunction in recipient mice. Mononuclear phagocytes populations expand in a phasic manner in the heart during pressure-overload. However, they are dispensable for the progression of remodeling and failure once significant hypertrophy is evident and blood monocytosis has normalized.