Treatment with a DC-SIGN ligand reduces macrophage polarization and diastolic dysfunction in the aging female but not male mouse hearts.
Treatment with a DC-SIGN ligand reduces macrophage polarization and diastolic dysfunction in the aging female but not male mouse hearts.
复制标题
DOI：
10.1007/s11357-020-00255-4
复制
发表时间：
2021-04
期刊：
影响因子：
5.6
通讯作者：
Cieslik KA
中科院分区：
文献类型：
--
作者：
Trial J;Diaz Lankenau R;Angelini A;Tovar Perez JE;Taffet GE;Entman ML;Cieslik KA
老年心脏舒张功能障碍是由炎症和间质纤维化引起的心室僵硬度增加引起的。舒张功能障碍导致射血分数保留性心力衰竭（HFpEF），这在老年人群中更常见于女性。本报告研究了其在老龄C57 BL/6 J小鼠中的12周进展，并将其发展与巨噬细胞极化和胶原沉积的变化相关联。用树突状细胞特异性细胞间粘附分子-3-抓取非整联蛋白（DC-SIGN）配体1（DCSL 1，一种抗炎剂）或生理盐水注射老年C57 BL/6 J小鼠12周。治疗前、治疗后4周和12周进行超声心动图和多普勒测量。DCSL 1可防止女性舒张功能障碍随时间的恶化，但在男性中则不然。通过流式细胞术分析的心脏单细胞悬液显示炎性浸润的变化：（1）在雄性中，与雌性相比，具有增加的促炎特征的白细胞总数增加，并且它们对DCSL 1没有反应;（2）相比之下，DCSL 1处理导致雌性中巨噬细胞极化转变为抗炎表型。值得注意的是，DCSL 1优先靶向肿瘤坏死因子-α（TNFα+）促炎巨噬细胞。促炎性巨噬细胞极化的减少伴随着心脏中胶原蛋白含量的减少。小鼠心脏舒张功能障碍在雌性中更为严重，并且与心脏组织中巨噬细胞极化的独特变化相关。DCSL 1治疗可减轻炎症、心脏功能和纤维化的变化。老年雌性小鼠舒张功能障碍的特征与老年女性相似。本文的在线版本（10.1007/s11357-020-00255-4）包含补充材料，可供授权用户使用。
Cardiac diastolic dysfunction in aging arises from increased ventricular stiffness caused by inflammation and interstitial fibrosis. The diastolic dysfunction contributes to heart failure with preserved ejection fraction (HFpEF), which in the aging population is more common in women. This report examines its progression over 12 weeks in aging C57BL/6J mice and correlates its development with changes in macrophage polarization and collagen deposition. Aged C57BL/6J mice were injected with dendritic cell–specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) ligand 1 (DCSL1, an anti-inflammatory agent) or saline for 12 weeks. Echo and Doppler measurements were performed before and after 4 and 12 weeks of treatment. DCSL1 prevented the worsening of diastolic dysfunction over time in females but not in males. Cardiac single cell suspensions analyzed by flow cytometry revealed changes in the inflammatory infiltrate: (1) in males, there was an increased total number of leukocytes with an increased pro-inflammatory profile compared with females and they did not respond to DCSL1; (2) by contrast, DCSL1 treatment resulted in a shift in macrophage polarization to an anti-inflammatory phenotype in females. Notably, DCSL1 preferentially targeted tumor necrosis factor-α (TNFα+) pro-inflammatory macrophages. The reduction in pro-inflammatory macrophage polarization was accompanied by a decrease in collagen content in the heart. Age-associated diastolic dysfunction in mice is more severe in females and is associated with unique changes in macrophage polarization in cardiac tissue. Treatment with DCSL1 mitigates the changes in inflammation, cardiac function, and fibrosis. The characteristics of diastolic dysfunction in aging female mice mimic similar changes in aging women. The online version of this article (10.1007/s11357-020-00255-4) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
5.2
作者：
de Arellano, Maria Luisa Barcena;Pozdniakova, Sofya;Regitz-Zagrosek, Vera
通讯作者：
Regitz-Zagrosek, Vera
影响因子：
4.9
作者：
Chong BF;Tseng LC;Hosler GA;Teske NM;Zhang S;Karp DR;Olsen NJ;Mohan C
通讯作者：
Mohan C
影响因子：
15
作者：
Borrok, M. Jack;Kiessling, Laura L.
通讯作者：
Kiessling, Laura L.
影响因子：
1.2
作者：
Granillo, Alejandro;Pena, Celia A.;Taffet, George E.
通讯作者：
Taffet, George E.
影响因子：
5
作者：
Cieslik KA;Taffet GE;Carlson S;Hermosillo J;Trial J;Entman ML
通讯作者：
Entman ML