β-Adrenergic receptors (βAR) regulate normal and pathophysiological heart function through their impact on contractility. βAR are also regulators of immune function where they play a unique role depending on the disease condition and immune cell type. Emerging evidence suggests an important role for the β2AR subtype in regulating remodeling in the pathological heart, however, the importance of these responses has never been examined. In heart failure, catecholamines are elevated, leading to chronic βAR activation and contributing to the detrimental effects in the heart. We hypothesized that immune cell β2AR plays a critical role in the development of heart failure in response to chronic catecholamine elevations through their regulation of immune cell recruitment. To test this, chimeric mice were generated by performing bone marrow transplant (BMT) experiments using WT or β2AR knockout (KO) donors. WT and β2ARKO BMT mice were chronically administered the βAR agonist isoproterenol. Immune cell recruitment to the heart was examined by histology and flow cytometry. Numerous changes in immune cell recruitment were observed with isoproterenol administration in WT BMT mice including pro-inflammatory myeloid populations and lymphocytes with macrophages made up the majority of immune cells in the heart and which were absent in β2ARKO BMT animal. β2ARKO BMT mice had decreased cardiomyocyte death, hypertrophy and interstitial fibrosis following isoproterenol treatment, which culminated in improved function. These findings demonstrate an important role for immune cell β2AR expression in the heart's response to chronically elevated catecholamines.

中文翻译：

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免疫细胞 β2-肾上腺素能受体有助于心力衰竭的发展

β-肾上腺素能受体 (βAR) 通过对收缩力的影响来调节正常和病理生理的心脏功能。βAR 也是免疫功能的调节剂，它们根据疾病状况和免疫细胞类型发挥独特的作用。新出现的证据表明 β2AR 亚型在调节病理性心脏重塑中起重要作用，然而，这些反应的重要性从未被研究过。在心力衰竭中，儿茶酚胺升高，导致慢性 βAR 激活并导致对心脏的不利影响。我们假设免疫细胞 β2AR 通过调节免疫细胞募集在慢性儿茶酚胺升高引起的心力衰竭的发展中起关键作用。为了测试这个，嵌合小鼠是通过使用 WT 或 β2AR 敲除 (KO) 供体进行骨髓移植 (BMT) 实验产生的。WT 和 β2ARKO BMT 小鼠长期服用 βAR 激动剂异丙肾上腺素。通过组织学和流式细胞术检查免疫细胞募集到心脏。在 WT BMT 小鼠中使用异丙肾上腺素观察到免疫细胞募集的许多变化，包括促炎性骨髓细胞群和具有巨噬细胞的淋巴细胞，它们构成了心脏中的大部分免疫细胞，而在 β2ARKO BMT 动物中不存在这些变化。β2ARKO BMT 小鼠在异丙肾上腺素治疗后减少了心肌细胞死亡、肥大和间质纤维化，最终改善了功能。这些发现表明免疫细胞β2AR在心脏中的表达具有重要作用。