PDE4 Phosphodiesterases in Cardiovascular Diseases: Key Pathophysiological Players and Potential Therapeutic Targets

Figures

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  Figure 1. PDE4 in disease. This scheme depicts the diseases that have been associated with disturbances in PDE4 expression/activity. HF: Heart failure; MI/R myocardial ischemia/reperfusion; COPD: chronic obstructive pulmonary disease; CNS: central nervous system. This figure was partly generated using Servier Medical Art provided by Servier, licenced under a Creative Commons Attribution 3.0 unported license.

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  Figure 2. Modular structure of the PDE4 family enzymes. The structure common to the 4 members of the PDE4 family is shown, including UCR1 and UCR2 domains, LR1 and LR2 regions, and the catalytic domain. The isoforms generated by the use of different promoters or by alternative splicing that give rise to the long, short and super-short forms of these enzymes are shown schematically. Phosphorylation sites for PKA and ERK are indicated. The ERK phosphorylation site is not present in PDE4A variants. ERK: Extracellular signal-regulated kinase; LR: linker region; PKA: protein kinase A; UCR: Upstream Conserved Regions.

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  Figure 3. Potential effects of PDE4 inhibition on endothelial cells and vascular smooth muscle cells. LOX-1: Lectin-like oxidized low-density lipoprotein receptor-1.