Coutard Michèle, Osborne-Pellegrin Mary, Fontaine Vincent, Jacob Marie-Paule, Michel Jean-Baptiste
INSERM U698, Hôpital Xavier Bichat, Paris, France.
J Vasc Res. 2006;43(3):217-28. doi: 10.1159/000091101. Epub 2006 Jan 20.
The higher incidence of cerebral aneurysms (CAs) induced by enhanced arterial blood flow in Long Evans (LE) compared to Brown Norway (BN) rats suggests that intrinsic differences in high-flow arterial remodeling may be involved in determining CA susceptibility. Some aspects of this remodeling were compared in LE and BN rats after creation of an abdominal aortocaval fistula (ACF).
At 4 days with ACF, aortic luminal cross-sectional area (LCSA) determined by morphometry was increased by 20% in LE but not in BN rats. mRNA levels, determined by RT-PCR, were higher in LE than in BN rats for collagen alpha1(I), collagen alpha1(III), MMP2 and its inhibitor TIMP1 at 19 days with ACF. Nitric oxide synthase (NOS) mRNA levels were higher in LE rats at 4 days for the inducible (NOS2) isoform and at 4 and 19 days for the neuronal (NOS1) isoform. Aortic LCSA and NOS1 mRNA levels were tightly correlated and NOS inhibition prevented ACF-induced aortic remodeling in the LE rat. MMP2 and MMP7 activity, evaluated by zymography at 4 days with ACF, did not greatly differ between BN and LE.
These data suggest that a higher intrinsic ability for high-flow-induced arterial enlargement associated with NOS gene overexpression may be a possible genetic determinant in CA susceptibility.
与布朗挪威（BN）大鼠相比，长 Evans（LE）大鼠因动脉血流增强导致的脑动脉瘤（CA）发病率更高，这表明高流量动脉重塑的内在差异可能与 CA 易感性的决定有关。在创建腹主动脉腔静脉瘘（ACF）后，对 LE 和 BN 大鼠的这种重塑的某些方面进行了比较。
在 ACF 术后 4 天，通过形态计量学测定的主动脉管腔横截面积（LCSA）在 LE 大鼠中增加了 20%，而在 BN 大鼠中未增加。在 ACF 术后 19 天，通过 RT-PCR 测定，LE 大鼠中胶原蛋白α1（I）、胶原蛋白α1（III）、MMP2 及其抑制剂 TIMP1 的 mRNA 水平高于 BN 大鼠。在术后 4 天，诱导型（NOS2）亚型的一氧化氮合酶（NOS）mRNA 水平在 LE 大鼠中较高，在术后 4 天和 19 天，神经元型（NOS1）亚型的 NOS mRNA 水平在 LE 大鼠中较高。主动脉 LCSA 和 NOS1 mRNA 水平密切相关，NOS 抑制可阻止 LE 大鼠中 ACF 诱导的主动脉重塑。在 ACF 术后 4 天通过酶谱法评估的 MMP2 和 MMP7 活性在 BN 和 LE 大鼠之间没有很大差异。
这些数据表明，与 NOS 基因过表达相关的高流量诱导动脉扩张的较高内在能力可能是 CA 易感性的一个可能的遗传决定因素。
