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

Abstract

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 ± 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.

Interrelationship of canonical and non-canonical Wnt signalling pathways in chronic metabolic diseases

“…Recently, Pandey and Chandravati 100 have suggested that Wnt signalling can complement public health initiatives in predicting occlusive vascular disease (restenosis after coronary artery bypass graft surgery) which is a major public health problem in the United States. Identification of new molecular mechanisms in coordination with clinical data is crucial in the development of cost-effective biomarkers for this at-risk population.…”

“…Identification of new molecular mechanisms in coordination with clinical data is crucial in the development of cost-effective biomarkers for this at-risk population. 100 Wnt signalling contributes to multiple levels of atherosclerosis pathogenesis: initial endothelial dysfunction, plaque instability and size of the lipid core; however, the full contribution of non-canonical and canonical Wnts in the development of atherosclerosis and CVD has yet to be elucidated in detail. Thus, therapeutics targeting Wnt signalling may provide a novel way to combat atherosclerosis.…”

Serum Wnt5a Level is Associated with In-Stent Restenosis in PCI Patients

“…It is reported that the stable neointima contains 20% VSMCs [20], suggests that VSMCs play an important role in ISR. Pandey et al found that Wnt5a mRNA was expressed in human VSMCs, as well as its receptors, such as Fzd1, Fzd2 and Fzd5 [21]. This result suggests that Wnt5a may be implicated in ISR via regulating VSMCs functions.…”