白细胞介素-1 受体 I 型促进小鼠与衰老相关的心肌病的发展。
The interleukin-1 receptor type I promotes the development of aging-associated cardiomyopathy in mice.
机构信息
VCU Health Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA; Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
VCU Health Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA; School of Pharmacy, Virginia Commonwealth University, Richmond, VA, USA.
出版信息
Cytokine. 2022 Mar;151:155811. doi: 10.1016/j.cyto.2022.155811. Epub 2022 Jan 25.
BACKGROUND
Aging is associated with metabolic and structural changes causing heart failure with preserved ejection fraction (HFpEF). Interleukin-1 (IL-1) is a pro-inflammatory cytokine involved in aging-related inflammation.
OBJECTIVE
We sought to determine whether IL-1 mediates aging-related changes in the heart, as seen in HFpEF.
METHODS
We studied age-matched young (4-month-old), middle-aged (14-month-old), and old (23-month-old) wild-type (WT) C57BL/6J and IL-1 receptor type I deficient (IL1RI-KO) male mice. Echocardiography was used to evaluate left ventricular (LV) dimensions and systolic/diastolic function, and a pressure transducer was used to measure the LV end-diastolic pressure. Picrosirius red stain was used to assess for myocardial interstitial fibrosis (MIF) at pathology.
RESULTS
WT and IL-1RIKO mice showed a normal cardiac phenotype at young age, without any differences between the two groups. With aging, the WT mice developed LV concentric hypertrophy (as measured by a significant increase in LV mass [+42%, P < 0.01] and relative wall thickness [+34%, P < 0.01]), whereas the aging IL-1RI-KO mice did not. With aging, the WT mice also developed diastolic dysfunction (as measured by a significant increase in isovolumetric relaxation time [+148%, P < 0.01] and a significantly higher LV end-diastolic pressure [+174%, P < 0.01]), whereas the aging IL1RI-KO did not. Aged WT mice showed a significant increase in MIF (+124%, P < 0.01) at cardiac pathology, whereas the aging IL-1RI-KO did not.
CONCLUSIONS
Genetically-modified mice lacking the IL-1RI receptor, not responsive to IL-1, are protected from aging-related LV hypertrophy, fibrosis, and diastolic dysfunction. These data support a central role of IL-1 in the pathophysiology of aging-related HFpEF.
背景
衰老与代谢和结构变化有关，导致射血分数保留的心力衰竭（HFpEF）。白细胞介素-1（IL-1）是一种参与衰老相关炎症的促炎细胞因子。
目的
我们试图确定 IL-1 是否介导了 HFpEF 中所见的与衰老相关的心脏变化。
方法
我们研究了年龄匹配的年轻（4 个月大）、中年（14 个月大）和老年（23 个月大）野生型（WT）C57BL/6J 和白细胞介素-1 受体 I 缺陷（IL1RI-KO）雄性小鼠。超声心动图用于评估左心室（LV）尺寸和收缩/舒张功能，压力传感器用于测量 LV 舒张末期压力。苦味酸天狼星红染色用于评估病理学中的心肌间质纤维化（MIF）。
结果
WT 和 IL-1RIKO 小鼠在年轻时表现出正常的心脏表型，两组之间没有差异。随着年龄的增长，WT 小鼠出现 LV 向心性肥大（通过 LV 质量的显著增加[+42%，P<0.01]和相对壁厚度的显著增加[+34%，P<0.01]），而衰老的 IL-1RI-KO 小鼠则没有。随着年龄的增长，WT 小鼠也出现舒张功能障碍（通过等容松弛时间的显著增加[+148%，P<0.01]和 LV 舒张末期压力的显著增加[+174%，P<0.01]），而衰老的 IL1RI-KO 则没有。心脏病理学显示，老年 WT 小鼠的 MIF 显著增加（+124%，P<0.01），而衰老的 IL-1RI-KO 则没有。
结论
缺乏白细胞介素-1 受体（对白细胞介素-1 无反应）的基因修饰小鼠对衰老相关的 LV 肥大、纤维化和舒张功能障碍具有保护作用。这些数据支持白细胞介素-1 在衰老相关 HFpEF 的病理生理学中的核心作用。
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