Pde4b-KO Mouse

Pde4b, a member of the phosphodiesterase (PDEs) protein family, is a major cyclic adenosine monophosphate (cAMP)-metabolizing enzyme [3]. PDE4 enzymes hydrolyze intracellular cAMP, and Pde4b is one of its 4 subtypes (A-D). cAMP signaling is involved in numerous cellular processes, making Pde4b's function crucial in regulating these pathways [1].

In acute myocardial infarction, Pde4b deletion in mice strikingly reduced infarct size and improved cardiac function after myocardial ischemia-reperfusion (MI/R) injury. Pde4b in bone marrow-derived cells and vascular Pde4b promoted MI/R injury. Mechanistically, it mediated neutrophil-endothelial cell interaction, PKA-dependent expression of cell adhesion molecules, neutrophil cardiac infiltration, and release of proinflammatory cytokines. It also promoted coronary microcirculatory obstruction and vascular permeability [1]. In heart failure, cardiac overexpression of Pde4b in transgenic mouse lines had different effects. A moderate increase was cardioprotective, preventing systolic dysfunction, apoptosis, and fibrosis induced by chronic isoproterenol treatment or transverse aortic constriction, while a markedly higher overexpression led to hypertrophy, dilatation, and premature death [2].

In summary, Pde4b plays a significant role in regulating cAMP-related biological processes. Studies using gene knockout (KO) or conditional knockout (CKO) mouse models have revealed its involvement in acute myocardial infarction and heart failure. These models have been instrumental in understanding how Pde4b contributes to these disease conditions, highlighting its potential as a therapeutic target for treating cardiovascular diseases [1,2].

References:

1. Wan, Qing, Xu, Chuansheng, Zhu, Liyuan, Liu, De-Pei, Wang, Miao. 2022. Targeting PDE4B (Phosphodiesterase-4 Subtype B) for Cardioprotection in Acute Myocardial Infarction via Neutrophils and Microcirculation. In Circulation research, 131, 442-455. doi:10.1161/CIRCRESAHA.122.321365. https://pubmed.ncbi.nlm.nih.gov/35899614/

2. Karam, Sarah, Margaria, Jean Piero, Bourcier, Aurélia, Leroy, Jérôme, Vandecasteele, Grégoire. 2020. Cardiac Overexpression of PDE4B Blunts β-Adrenergic Response and Maladaptive Remodeling in Heart Failure. In Circulation, 142, 161-174. doi:10.1161/CIRCULATIONAHA.119.042573. https://pubmed.ncbi.nlm.nih.gov/32264695/

3. Su, Yue, Ding, Jiaxiang, Yang, Fan, Zhou, Huan, Li, Hongtao. 2022. The regulatory role of PDE4B in the progression of inflammatory function study. In Frontiers in pharmacology, 13, 982130. doi:10.3389/fphar.2022.982130. https://pubmed.ncbi.nlm.nih.gov/36278172/