PDE-Mediated Cyclic Nucleotide Compartmentation in Vascular Smooth Muscle Cells: From Basic to a Clinical Perspective

Cardiovascular diseases are important causes of mortality and morbidity worldwide. Vascular smooth muscle cells (SMCs) are major components of blood vessels and are involved in physiologic and pathophysiologic conditions. In healthy vessels, vascular SMCs contribute to vasotone and regulate blood flow by cyclic nucleotide intracellular pathways. However, vascular SMCs lose their contractile phenotype under pathological conditions and alter contractility or signalling mechanisms, including cyclic nucleotide compartmentation. In the present review, we focus on compartmentalized signaling of cyclic nucleotides in vascular smooth muscle. A deeper understanding of these mechanisms clarifies the most relevant axes for the regulation of vascular tone. Furthermore, this allows the detection of possible changes associated with pathological processes, which may be of help for the discovery of novel drugs.