Immune cell β2-adrenergic receptors contribute to the development of heart failure.
Immune cell β2-adrenergic receptors contribute to the development of heart failure.
复制标题
免疫细胞β2-肾上腺素能受体有助于心力衰竭的发展。
DOI：
10.1152/ajpheart.00243.2021
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Grisanti,LaurelA
中科院分区：
文献类型：
--
作者：
Tanner,MilesA;Maitz,CharlesA;Grisanti,LaurelA
β-肾上腺素能受体（β AR）通过影响收缩性调节正常和病理生理心脏功能。β AR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亚型在调节病理心脏重塑中的重要作用;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激活并导致心脏中的有害作用。我们假设免疫细胞β2AR通过调节免疫细胞浸润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。为了测试这一点，通过使用野生型（WT）或β2AR敲除（KO）供体进行骨髓移植（BMT）实验来产生嵌合小鼠。WT和β2ARKO BMT小鼠长期给予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向心脏的募集。在WT BMT小鼠中给予异丙肾上腺素后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淋巴细胞，其中巨噬细胞构成心脏中的大部分免疫细胞，而β2ARKO BMT动物中不存在巨噬细胞。异丙肾上腺素治疗后，β2ARKO BMT小鼠心肌细胞死亡、肥大和间质纤维化减少，最终功能改善。这些发现表明免疫细胞β2-肾上腺素能受体（β 2-adrenergic receptor，β2ARs）表达在心脏对慢性升高的儿茶酚胺的反应中具有重要作用。缺乏免疫细胞β2AR的小鼠心脏免疫细胞浸润减少，主要是促炎性巨噬细胞群。这种减少最终导致心脏损伤减少，心肌细胞死亡减少，间质纤维化和肥大减少，功能改善，表明β2AR对免疫反应的调节在心脏对持续βAR刺激的反应中起着重要作用。https://ajpheart.podbean.com/e/immune-cell-%ce%b22-adrenergic-receptor-in-the-heart/
β-Adrenergic receptors (βARs) regulate normal and pathophysiological heart function through their impact on contractility. βARs 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 infiltration. To test this, chimeric mice were generated by performing bone marrow transplant (BMT) experiments using wild-type (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 proinflammatory 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, culminating in improved function. These findings demonstrate an important role for immune cell β2AR expression in the heart’s response to chronically elevated catecholamines.NEW & NOTEWORTHYImmune cell β2-adrenergic receptors (β2ARs) are important for proinflammatory macrophage infiltration to the heart in a chronic isoproterenol administration model of heart failure. Mice lacking immune cell β2AR have decreased immune cell infiltration to their heart, primarily proinflammatory macrophage populations. This decrease culminated to decreased cardiac injury with lessened cardiomyocyte death, decreased interstitial fibrosis and hypertrophy, and improved function demonstrating that β2AR regulation of immune responses plays an important role in the heart’s response to persistent βAR stimulation.Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/immune-cell-%ce%b22-adrenergic-receptor-in-the-heart/.