General Research Interests: Regulation and function of cyclic nucleotide phosphodiesterases in the cardiovascular system. Second messenger cyclic nucleotides (cAMP and cGMP) regulate many signaling pathways in the cardiovascular system. For example, the vascular tone, smooth muscle cell growth, and cardiac muscle contractility are all regulated by cyclic nucleotide signaling. We are interested in phosphodiesterases (PDEs), the enzymes that break down cyclic nucleotides and thus control the amplitude, duration, and compartmentalization of cyclic nucleotide signaling in the cell. It has become increasingly clear that cyclic nucleotide degradation by PDEs is not a constitutive function of the cell, but rather a highly regulated one controlled by different mechanisms in different physiological and pathological circumstances. PDE regulation and function is further complicated by the fact that there are more than 50 individual PDEs belonging to 11 different PDE families, yet our understanding of the physiological function of each PDE is far from complete. PDEs have been demonstrated to be good pharmacological targets for therapeutic agents due to the presence of multiple structurally different, tissue-specific, differentially regulated, and functionally distinct isozymes. Several drugs, such as Viagra, have been shown to have unique specific effects via selectively inhibit individual PDE isozymes. Our focus has been on determining the regulation and function of individual PDE isozymes in cardiovascular diseases such as hypertension, atherosclerosis, heart failure, and cardiovascular inflammatory diseases. Ongoing and future studies using in vitro and in vivo approaches will focus on the various roles of PDEs in cardiovascular physiology and pathology, which may provide new therapeutic information for tissue specific interventions in cardiovascular diseases.
