408 - Cinnamic Aldehyde Inhibits PDGF-Induced Migration and Proliferation of Smooth Muscle Cells, and Neointimal Hyperplasia in Diabetic Rats

Abstract

Introduction Patients with Diabetes Mellitus have a higher risk of developing peripheral arterial and cardiovascular disease, which is partially attributed to inflammation, increased reactive oxygen species, and endothelial cell dysfunction. Nrf2 (NF-E2-related factor 2) plays a key role in protecting against environmental stress by inducing expression of detoxification and antioxidant enzymes. Cinnamic aldehyde (CA) is a small molecule Nrf2 activator. Our goal is to assess the protective effect of CA against diabetes-induced vascular damage. We hypothesize that CA will activate the Nrf2 pathway, inhibit proliferation and migration of diabetic vascular smooth muscle cells in vitro, as well as protect against restenosis in vivo after carotid balloon injury in Zucker Diabetic Fatty (ZDF) rats. Methods Arterial smooth muscle cells from ZDF rats (D-SMC) were isolated and cultured in high glucose medium. The effect of CA at different concentrations (0.1, 1, 10, 50, and 100 μM) on platelet-derived growth factor (PDGF)-induced cell proliferation was assessed by the MTT assay and by counting viable cells. Cell migration was evaluated following CA treatment via the scratch assay. A Muse-based assay was used to determine the effect of 100 μM CA on the cell cycle. Nrf2 translocation was studied by Western blotting of the nuclear fraction, and immunofluorescence after CA treatment (100 μM). Sulforaphane (4 μM) was used as a positive control. 10 week-old ZDF rats were fed a high fat diet for one month to induce diabetes. The balloon carotid injury model was performed with or without periadventitial application of CA (100 μM in 150 μl of Pluronic gel). Two weeks after surgery the carotids were harvested for morphometric analysis. Results CA (100 μM) inhibited PDGF-induced cell proliferation of D-SMC by 50%, assessed by both MTT (P Conclusion These data show that CA has a protective effect, inhibiting proliferation and migration of diabetic arterial smooth muscle cells. CA also has a protective effect in vivo inhibiting the development of neointimal hyperplasia. This inhibition suggests that CA could afford protection against vascular restenosis in diabetic arteries after vascular interventions.