Wnt signaling cascade in restenosis: a potential therapeutic target of public health relevance in a North American cohort of Nebraska State

Cardiovascular disease is a leading cause of morbidity and mortality in United States, including Nebraska. Neointimal hyperplasia leading to restenosis is a major public health problem. Identification of key signaling molecules in biochemical pathways is an attractive strategy for development of predictive biomarkers in occlusive vascular diseases (OVD). Our pilot study aimed to identify the role of Wnt-frizzled signaling in restenosis in a North American cohort. North American patients (n = 9) undergoing coronary artery bypass graft surgery at Nebraska Heart Institute, Lincoln, were enrolled. Human saphenous veins (SV) (n = 9) and left internal mammary arteries (LIMA) (n = 9) received post-surgery at Creighton University, Omaha, were harvested using Collagenase-IV digestion method. Isolated primary VSMCs were cultured for 3-4 weeks, and passages P3-P7, were used for molecular biology experiments. The study was approved by the Institutional Review Board. RNA was extracted using trizol method and mRNA transcripts were identified using reverse transcriptase-polymerase chain reaction followed by 2 % agarose gel electrophoresis. Mean age of surgery patients (n = 9) was 60.3 years (SD +/- A 6.5 years). Wnt2 and Wnt5a mRNA transcripts were expressed in human VSMCs; however, Wnt1, Wnt4 and Wnt11 mRNA were not expressed; beta-actin was used as an internal control. Receptor studies demonstrated the expression of Fzd1, Fzd2 and Fzd5 mRNA in hVSMCs. Our preliminary data implicates the public health significance of Wnt signaling in bypass graft patients in Nebraska. Future molecular biology approach-based community health studies targeting Wnt pathway may aid in the development of cost-effective predictive biomarkers for OVD susceptible populations.