β-Adrenoceptor activation affects galectin-3 as a biomarker and therapeutic target in heart disease

Myocardial fibrosis is a key histopathological component that drives the progression of heart disease leading to heart failure and constitutes a therapeutic target. Recent preclinical and clinical studies have implicated galectin-3 (Gal-3) as a pro-fibrotic molecule and a biomarker of heart disease and fibrosis. However, our knowledge is poor on the mechanism(s) that determine the blood level or regulate cardiac expression of Gal-3. Recent studies have demonstrated that enhanced beta-adrenoceptor activity is a determinant of both circulating concentration and cardiac expression of Gal-3. Pharmacological or transgenic activation of beta-adrenoceptors leads to increased blood levels of Gal-3 and up-regulated cardiac Gal-3 expression, effect that can be reversed with the use of beta-adrenoceptor antagonists. Conversely, Gal-3 gene deletion confers protection against isoprenaline-induced cardiotoxicity and fibrogenesis. At the transcription level, beta-adrenoceptor stimulation activates cardiac mammalian sterile-20-like kinase 1, a pivotal kinase of the Hippo signalling pathway, which is associated with Gal-3 up-regulation. Recent studies have suggested a role for the beta-adrenoceptor-Hippo signalling pathway in the regulation of cardiac Gal-3 expression thereby contributing to the onset and progression of heart disease. This implies a therapeutic potential of the suppression of Gal-3 expression. In this review, we discuss the effects of beta-adrenoceptor activity on Gal-3 as a biomarker and causative mediator in the setting of heart disease and point out pivotal knowledge gaps.