| First Author | Tanner MA | Year | 2021 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 321 |
| Issue | 4 | Pages | H633-H649 |
| PubMed ID | 34415184 | Mgi Jnum | J:310929 |
| Mgi Id | MGI:6762525 | Doi | 10.1152/ajpheart.00243.2021 |
| Citation | Tanner MA, et al. (2021) Immune cell beta2-adrenergic receptors contribute to the development of heart failure. Am J Physiol Heart Circ Physiol 321(4):H633-H649 |
| abstractText | beta-Adrenergic receptors (betaARs) regulate normal and pathophysiological heart function through their impact on contractility. betaARs 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 beta2AR 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 betaAR activation and contributing to the detrimental effects in the heart. We hypothesized that immune cell beta2AR 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 beta2AR knockout (KO) donors. WT and beta2ARKO BMT mice were chronically administered the betaAR 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 beta2ARKO BMT animal. beta2ARKO 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 beta2AR expression in the heart's response to chronically elevated catecholamines.NEW & NOTEWORTHY Immune cell beta2-adrenergic receptors (beta2ARs) are important for proinflammatory macrophage infiltration to the heart in a chronic isoproterenol administration model of heart failure. Mice lacking immune cell beta2AR 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 beta2AR regulation of immune responses plays an important role in the heart's response to persistent betaAR stimulation. |
