[Cyclic nucleotide phosphodiesterase IV expression, activity and targeting in cells of cardiovascular system].
Cyclic nucleotide second messages (cAMP and cGMP) play a central role in signal transduction and regulation of physiologic responses. The only way to inactivate them is to degrade them through the action of phosphodiesterases (PDEs). Recent advances show that PDE4, a cAMP specific phosphodiesterase, has specific functions in regulating the activities of the cardiovascular system. PDE4 is expressed in the cells of cardiovascular systems including cardiomyocytes, vascular smooth muscle cells, and vascular endothelial cells. The expression level of PDE4 is shown to be downregulated in the failure hearts, while it is upregulated in hypertrophied hearts. And PDE4 deficiency in mice is associated with a cardiac phenotype comprised of a progressive, age-related cardiomyopathy, accelerated heart failure after myocardial infarction and exercise-induced arrhythmias. Local levels of cAMP regulate the precise opening of the ryanodine receptor complex (RyR2) which releases calcium at the start of a heartbeat. Loss or inhibition of PDE4 activity increases calcium flow through RyR2, and causes leakiness and heart failure in mice. These finding may show us a new target for treating cardiovascular diseases.
Yan
Jun
J
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Zhu
Hai-Bo
HB
D000818:Animals; D002319:Cardiovascular System / Q000201:enzymology*; D000242:Cyclic AMP / Q000502:physiology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000201:enzymology; D032383:Myocytes, Cardiac / Q000201:enzymology; D058988:Phosphodiesterase 4 Inhibitors; D015398:Signal Transduction
D058988:Phosphodiesterase 4 Inhibitors; D000242:Cyclic AMP; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4