3-Hydroxybenzalde Inhibites Neointimal Hyperplasia In Vein Grafts Of Rabbits

Background and Objective Cardiovascular disease is the most common diseases.As the major component of cardiovascular disease,coronary heart disease is the most familiar reason for death in all cardiovascular diseases.,Coronary artery bypass grafting(CABG)is the main method of treatment for severe coronary heart disease.saphenous vein(SV)and left internal mammary artery(LIMA)are used in surgical operation.LIMA grafts usually have a high long-term patency rate,while the long-term patency rate of SV grafts are unoptimistic.3-hydroxybenzaldehyde(3-HBA)is the precursor of protocatechuic aldehyde(PCA),and it has been conformed that,PCA contains the cardiovascular protective effects.However,no study has been conducted to evalue the effects of 3-HBA on SV grafts.The objective of this study is to assess the effects of 3-HBA on autogenous vein grafts of rabbits and HSVSMCs,and farther find a new agent to prevent SV grafts failure after CABG.Methods 1.Human saphenous vein smooth muscle cells were cultured in vivo,and the treated group were intervened with 3-HBA for 24 h,while the control group with PBS.Cell proliferation was assayed by MTT,cell migrationwas observed by transwell chamber,cell apoptosis was checked by Flow Cytometry,and the phosphorylation of AKT was examined by western blot analysis.2.24 healthy New Zealand white rabbits(body weight 2000g-2500g)without limited to gender,were randomly devided into the treatment group and the control group,and each group was farther divided equally into two subgroup.Each subgroup contained six rabbits.After implementing jugular vein-to-artery bypass grafting surgery,the treatment group were injected by 3-HBA100mg/(kg?d)via ear vein,while the control group by saline.Administration lasted to the day before rabbits were sacrificed.After 2 or 4 weeks vein grafts were harvested.The thickness of neointima were mesuared by computer image analysis system,and western blot was used to detect the protein level p-AKT.Results 1.Compared with the control group,cell proliferation and migration of the treatment group was statistically supressed twenty-four hours later(p<0.05),and cell apoptosis was increased(p<0.05).Western blot found the level of p-AKT was significantly lessened in the treatment group compared with the control group(p<0.05).Twenty-four rabbits were successful with the bridge model without apparent infection of incisional wound.2.Two weeks later,the neointima thickness of the treatment group(76.57±6.76?m)was inhibited compared with the control group(87.32±6.89?m)(p=0.123),difference was not statistically significant.And the difference was higher at 4 weeks(45.39±9.41?m vs 134.07±18.80?m)(p<0.05),the difference had statistical significance.The expression of p-AKT of the treatment group was significantly lower compared with control group both two weeks and four weeks(p<0.05).Conclusion 3-HBA can inhibit neointima hyperplasia of rabbits after venous was transplanted to carotid artery,which may due to the downregulation of p-AKT expression,and the inhibition of smooth muscle cells migration andproliferation,and the induction of cell apoptosis.