Abstract 45: Reduced Vascular Remodeling and Improved Endothelial Function in Transglutaminase 2 Knock-Out Mice Treated with Angiotensin II

Transglutaminase 2 (TG2) may modulate cell-matrix interactions by inducing cross-linking of proteins. We previously demonstrated that angiotensin II (Ang II) positively regulated TG2 expression in vascular smooth muscle cells from SHR. Here we hypothesized that Ang II induces vascular remodeling in part through TG2. TG2-knockout mice (TG2-K/O, 8 weeks old, 6 for each group) and age-matched wild type (WT) control mice were treated or not with Ang II (400 ng/kg/min) for 14 days. Blood pressure (BP) was measured by tail-cuff method. Endothelium-dependent and -independent relaxation were assessed by concentration-response curves to acetylcholine (1 nM to 100 μM) ± L-NAME (100 μM) and sodium nitroprusside (10 nM to 1 mM) respectively, in mesenteric arteries pre-contracted with norepinephrine (10 μM). Media-to-lumen ratio (M/L) and cross sectional area (CSA) were evaluated on pressurized preparations. BP was higher in TG2-K/O mice compared to WT (120.3±1.3 mmHg vs 88.3±1.9 mmHg, P In conclusion, despite the higher BP values, TG2-K/O presented improved vascular remodeling compared to WT. Ang II failed to increase M/L and impair endothelial function in TG2-K/O. Hence TG2 may play a role in Ang II-induced vascular structural and functional alterations.