Abstract 305: Exogenous Vasohibin-2 Exacerbates Angiotensin II-induced Ascending Aortic Aneurysms

Objective: Chronic angiotensin II (AngII) infusion promotes both ascending (TAAs) and abdominal aortic aneurysms (AAAs) in mice. Previous studies demonstrated that vascular endothelial growth factor (VEGF) enhanced AngII-induced AAA formation, and VEGF significantly increased AngII-induced AAA diameter in hypercholesterolemic mice. Vasohibin-1 (VASH-1) is induced by VEGF and inhibits angiogenesis at the termination zone under various pathologic conditions such as those of tumors, arterial intimal thickening and retinal neovasucularization. In contrast, a VASH-1 homolog, Vasohibin-2 (VASH-2), promotes angiogenesis at the sprouting front. Therefore, we hypothesized that exogenous VASH-2 influences AngII-induced TAAs in normocholesterolemic mice. The purpose of this study was to examine whether VASH-2 influenced AngII-induced TAAs. Methods and Results: Male C57BL/6J mice (10 weeks old) were fed a normal laboratory diet. Mice were injected 10^9 plaque-forming unit VASH-2 or Lac Z expressing adenovirus (Ad) via tail vein every other week. They were also infused subcutaneously with either AngII (1,000 ng/kg/min) or saline by osmotic mini-pumps for 3 weeks. The study mice had 4 groups: AngII + Ad VASH-2 (n=23), AngII + Ad Lac Z (n=23), Saline + Ad VASH-2 (n=13), Saline + Ad Lac Z (n=9). There were no significant differences between 4 groups in body weight. Plasma total cholesterol and VEGF concentrations were significantly increased in AngII infused groups (P < 0.05). Mortality ratio was 8.7% in AngII + Ad VASH-2 group and 4.3% in AngII + Ad Lac Z group. Intima area of aortic arch was significantly larger in AngII + Ad VASH-2 group than in AngII + Ad Lac Z group (19.78 ± 0.40 mm^3 vs 17.70 ± 0.41 mm^3, P < 0.01). AngII infusion significantly increased ex vivo maximal diameters of abdominal aorta, but there was no significant difference between VASH-2- and Lac Z-injected mice. Conclusion: Exogenous VASH-2 exacerbated AngII-induced ascending aortic aneurysms in male C57BL/6 mice.

Aldehyded Dextran andε-Poly(L-lysine) Hydrogel as Nonviral Gene Carrier

Background. The expression term of the gene transfected in cells needs to belong enough inorder to make a gene therapy clinically effective. The controlled release of the transfected gene can be utilized. The new biodegradable hydrogel material created by 20 w/w% aldehyded dextran and 10 w/w%ε-poly(L-lysine) (ald-dex/PLL) was developed. We examined whether it could be as a nonviral carrier of the gene transfer.Methods. A plasmid (Lac-Z) was mixed with ald-dex/PLL. Anin vitrostudy was performed to assess the expression of Lac-Z with X-gal stain after gene transfer into the cultured 293 cells and bone marrow cells. As a control group, PLL was used as a cationic polymer.Results. We confirmed that the transfection efficiency of the ald-dex/PLL had a higher transfection efficiency than PLL in 293 cells (plasmid of 2 μg: ald-dex/PLL 1.1%, PLL 0.23%, plasmid of 16 μg: ald-dex/PLL 1.23%, PLL 0.48%). In bone marrow cells, we confirmed the expression of Lac-Z by changing the quantity of aldehyded dextran. In the groups using ald-dextran of the quantity of 1/4 and 1/12 of PLL, their transfection efficiency was 0.43% and 0.41%, respectively.Conclusions. This study suggested a potential of using ald-dex/PLL as a non-carrier for gene transfer.