**Author details**

serve to mitigate abnormal cellular migration and growth associated with CVD. Indeed, these early findings offer support for VASP and phosphorylated VASP species, as crucial cytoske‐ letal and signal transduction proteins, as capable of controlling deleterious vascular growth

Indeed, VASP holds great promise regarding its ability to control VSM growth underlying vascular disorders but represents just one of the many end-targets of cyclic nucleotide-driven cellular signals. Vascular cyclic AMP and cyclic GMP and their Ser/Thr kinases also have capacity to exert regulatory control over synthetic TGF-beta signaling [19] as well as other cellto-cell and focal adhesion/cytoskeletal proteins including gap junctional connexins [46,47], paxillin [34,48], G-actin and F-actin rations [34], and FAK [28,34]. We have also reported on capacities of these signals to regulate ECM-degrading MMPs as a potential route of action in VSM [34,49]. The broad influence of cyclic nucleotide signaling and its many end-target proteins including VASP and associated cytoskeletal components in VSM presents an attrac‐ tive and biologically feasible therapeutic strategy aimed against basic elements of CVD and

The paramount importance of CVD on morbidity and mortality in the United States and globally is clear, yet inefficiencies in the clinical translation of basic science findings show that the underlying mechanisms of CVD are still not completely known and fully effective therapies against CVD are still needed. Indeed, despite ample basic and clinical research, CVD preva‐ lence is estimated to increase 10% and the economic burden of CVD is projected to triple within the next 20 years with latest estimates that >40% of the adult US population will have some form of CVD by the year 2030 [50]. In our incessant search for possible targets to help control and possibly eliminate CVD, the pivotal influence of VSM growth in playing key roles in CVD pathogenesis is clear. We and others have focused our efforts on identifying and characterizing unique elements behind VSM biology and signaling under healthy as well as pathologic conditions, and findings to date reveal significant insights into many biochemical, molecular, and cellular elements foundational to CVD with perhaps that of cyclic nucleotide signaling at the forefront. Given its ubiquitous nature and multifaceted diverse functions, cyclic AMP and cyclic GMP and their downstream kinases and targets including VASP represent key elements capable of controlling deleterious vascular growth that serves as a basis for CVD. Only through persistent basic science and clinical investigation do we hope to fully understand these crucial factors that hold great promise in our seemingly never-ending struggle to combat and control

The authors would like to thank all individuals with whom we have worked over the years in this challenging yet exciting field of study. We would also like to acknowledge investigators

integral for CVD.

20 Muscle Cell and Tissue

CVD.

**Acknowledgements**

many forms of vascular dysfunction.

**10. Summary and conclusions**

Andrew W. Holt and David A. Tulis

\*Address all correspondence to: tulisd@ecu.edu

Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA
