IN SILICO ANALYSIS OF COMBINED THERAPEUTICS STRATEGY FOR HEART FAILURE
Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea
School of Electrical Engineering, University of Ulsan, Ulsan, Korea
In failing cardiac myocytes, chronic stimulation of β-adrenergic receptor (β-AR) due to the high level of circulating catecholamine secreted by activation of the sympathetic nervous system leads to desensitization and impaired β-AR responsiveness . Furthermore, chronic activation of β-adrenergic signaling pathway may result in altered expression and functional activity of β-AR, G-protein, adenylyl cyclase (AC), and G-protein receptor kinase . The alteration of this pathway makes the β-ARmediated cardiac response substantially blunt and ultimately delivers adverse biological signals . These molecular and biochemical alterations of the β-AR signaling pathway are common to the failing hearts despite the varying etiologies . Therefore, restoring the altered signaling pathway is a generally accepted notion to treat heart failure (HF), and actually, new therapeutic strategies have been developed based on this notion . Among those new therapeutic strategies, β-AR-blocking agent (β-blocker) is conceived as a standard therapy for patients with mild-to-moderate HF . The diastolic function of such patients gets worsened with decreasing cardiac ...