Pistea Adrian, Bakker Erik N T P, Spaan Jos A E, Hardeman Max R, van Rooijen Nico, VanBavel Ed
Department of Medical Physics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
J Vasc Res. 2008;45(1):10-8. doi: 10.1159/000109073. Epub 2007 Sep 26.
Hypertension is associated with inward remodeling of small arteries and decreased erythrocyte deformability, both impairing proper tissue perfusion. We hypothesized that these alterations depend on transglutaminases, cross-linking enzymes present in the vascular wall, monocytes/macrophages and erythrocytes.
Wild-type (WT) mice and tissue-type transglutaminase (tTG) knockout (KO) mice received the nitric oxide inhibitor Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME) to induce hypertension. After 1 week, mesenteric arteries from hypertensive WT mice showed a smaller lumen diameter (-6.9 +/- 2.0%, p = 0.024) and a larger wall-to-lumen ratio (11.8 +/- 3.5%, p = 0.012) than controls, whereas inward remodeling was absent in hypertensive tTG KO mice. After 3 weeks, the wall-to-lumen ratio was increased in WT (20.8 +/- 4.8%, p = 0.005) but less so in tTG KO mice (11.7 +/- 4.6%, p = 0.026), and wall stress was normalized in WT but not in tTG KO mice. L-NAME did not influence expression of tTG or an alternative transglutaminase, coagulation factor XIII (FXIII). Suppression of FXIII by macrophage depletion was associated with increased tTG in the presence of L-NAME. L-NAME treatment decreased erythrocyte deformability in the WT mice (-15.3% at 30 dynes/cm(2), p = 0.014) but not in the tTG KO mice.
Transglutaminases are involved in small artery inward remodeling and erythrocyte stiffening associated with nitric oxide inhibition-related hypertension.
高血压与小动脉的内向重塑及红细胞变形性降低有关，二者均会损害正常的组织灌注。我们推测这些改变取决于转谷氨酰胺酶，这是一种存在于血管壁、单核细胞/巨噬细胞及红细胞中的交联酶。
野生型（WT）小鼠和组织型转谷氨酰胺酶（tTG）基因敲除（KO）小鼠接受一氧化氮抑制剂盐酸N-甲基-L-精氨酸（L-NAME）以诱导高血压。1周后，与对照组相比，高血压WT小鼠的肠系膜动脉管腔直径更小（-6.9±2.0%，p = 0.024），壁腔比更大（11.8±3.5%，p = 0.012），而高血压tTG KO小鼠未出现内向重塑。3周后，WT小鼠的壁腔比增加（20.8±4.8%，p = 0.005），而tTG KO小鼠增加较少（11.7±4.6%，p = 0.026），WT小鼠的壁应力恢复正常，而tTG KO小鼠未恢复。L-NAME不影响tTG或另一种转谷氨酰胺酶凝血因子XIII（FXIII）的表达。在存在L-NAME的情况下，巨噬细胞耗竭对FXIII的抑制与tTG增加有关。L-NAME处理使WT小鼠的红细胞变形性降低（在30达因/厘米²时降低-15.3%，p = 0.014），但对tTG KO小鼠无影响。
转谷氨酰胺酶参与了与一氧化氮抑制相关高血压有关的小动脉内向重塑和红细胞僵硬过程。
