The Roles of Phosphodiesterase (PDE) 3A and 3B as Regulators of Cardiac Function in Disease
Year: 2014
Type: dissertation
Abstract: Cyclic nucleotide phosphodiesterases (PDEs) are enzymes that hydrolyze the 3'-5'-phosphodiester bonds of cAMP and/or cGMP. PDE3 family variants (PDE3A, PDE3B) are highly expressed in the heart. The roles of PDE3A, and PDE3B as regulators of cardiac function in disease have not been definitively established. We investigated the roles of PDE3A and PDE3B as regulators of cardiac function in the setting of heart failure (HF) of non-ischemic etiology. PDE3A and not PDE3B protein expression was elevated in failing hearts subjected to sustained biomechanical stress (pressure-overload). Chronic ablation of PDE3A and not PDE3B activity attenuated cardiac contractile dysfunction and pathological remodelling induced by pressure-overload. We propose ablation of PDE3A activity to prevent functional deterioration and compensatory remodelling induced by chronic biomechanical stress by stimulating ANP release from cardiac myocytes, and consequently enhancing paracrine and endocrine activities of ANP. Accordingly, we propose PDE3A to negatively regulate ANP release from cardiac myocytes.
Source: TSpace (University of Toronto)
Author: Nazari Polidovitch
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2779380458