Immune cell b2-adrenergic receptors contribute to the development of heart failure
Miles A. Tanner, Charles A. Maitz, Laurel A. GrisantiAmerican Journal of Physiology - Heart and Circulatory Physiology2021
B-Adrenergic receptors (bARs) regulate normal and pathophysiological heart function through their impact on contractility. bARs 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 b2AR 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 bAR activation and contributing to the detrimental effects in the heart. We hypothesized that immune cell b2AR 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 b2AR knockout (KO) donors. WT and b2ARKO BMT mice were chronically administered the bAR 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 b2ARKO BMT animal. b2ARKO 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 b2AR expression in the heart’s response to chronically elevated catecholamines.