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.