Novel protein kinase targets in vascular smooth muscle therapeutics

•Abnormal vascular smooth muscle (VSM) growth is foundational to cardiovascular disease.•Cyclic AMP and cyclic GMP operate primarily through PKA and PKG, respectively.•PKA and PKG signal through many effectors including VASP during VSM growth.•VASP may represent a novel target for precision medicine in cardiovascular disease.

Many signaling factors have been identified over the years that serve as mechanistic foundations for the pathogenesis and/or maintenance of cardiovascular disease (CVD). Of these, cyclic nucleotide-driven protein kinases in vascular smooth muscle (VSM) are of essential importance. Comprised primarily of cyclic AMP-dependent and cyclic GMP-dependent protein kinases, these ubiquitous signaling molecules have capacity to operate through numerous downstream effectors including vasodilator-stimulated phosphoprotein (VASP) to control aberrant VSM growth elemental to CVD. As more information is gathered regarding genetic, biochemical, molecular and cellular makeup of CVD including VSM cyclic nucleotide-dependent protein kinases and VASP, advances will be made in precision medicine by identifying more precise therapeutic targets to enhance clinical decision making.