Angiotensin II activates matrix metalloproteinase type II and mimics age-associated carotid arterial remodeling in young rats
Angiotensin II activates matrix metalloproteinase type II and mimics age-associated carotid arterial remodeling in young rats
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DOI：
10.1016/s0002-9440(10)61229-1
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发表时间：
2005-11-01
影响因子：
6
通讯作者：
Lakatta, EG
中科院分区：
文献类型：
--
作者：
Wang, MY;Zhang, J;Lakatta, EG
血管紧张素 II (Ang II)、II 型基质金属蛋白酶 (MMP2) 和交感神经活性的增加伴随着与年龄相关的动脉重塑。为了分析这种关系，我们给年轻（8 个月大）的大鼠注射了低剂量的 Ang II。这增加了颈动脉 MMP2 转录、翻译和激活，以及转化生长因子-β 1 活性和胶原蛋白沉积。较高的血管紧张素II浓度使动脉压升高至未治疗的老年（30个月大）大鼠的水平，导致颈动脉中膜增厚和血管平滑肌细胞（VSMC）内膜浸润。离体后，Ang II 使年轻大鼠的颈动脉环中的 MMP2 活性增加到未治疗的老年大鼠的颈动脉环中。 Ang II 还增加了年轻大鼠早期传代的 VSMC 侵入合成基底膜的能力，类似于来自年老大鼠的未经处理的 VSMC。 MMP 抑制剂 GM6001 和 AT(1) 受体拮抗剂氯沙坦可抑制这些作用。 α-肾上腺素受体激动剂苯肾上腺素增加动脉 Ang II 蛋白，导致 MMP2 激活以及内膜和中膜增厚。体外将年轻 VSMC 暴露于去氧肾上腺素后，Ang II 蛋白和 MMP2 活性增加至年老 VSMC 的水平；氯沙坦消除了这些影响。因此，Ang Pi 诱导的 MMP2、转化生长因子-β 1、胶原蛋白和 VSMC 的作用是伴随年龄增长的动脉重塑的核心。
Increased angiotensin II (Ang II), matrix metalloproteinase type II (MMP2), and sympathetic activity accompany age-associated arterial remodeling. To analyze this relationship, we infused a low subpressor dose of Ang II into young (8 months old) rats. This increased carotid arterial MMP2 transcription, translation, and activation, as well as transforming growth factor-beta 1 activity and collagen deposition. A higher Ang II concentration, which increased arterial pressure to that of old (30 months old) untreated rats, produced carotid media thickening and intima infiltration by vascular smooth muscle cells (VSMCs). Ex vivo, Ang II increased MMP2 activity in carotid rings from young rats to that of untreated old rats. Ang II also increased the ability of early passage VSMCs from young rats to invade a synthetic basement membrane, similar to that of untreated VSMCs from old rats. The MMP inhibitor GM6001 and the AT(1) receptor antagonist Losartan inhibited these effects. The alpha-adrenoreceptor agonist phenylephrine increased arterial Ang II protein, causing MMP2 activation and intima and media thickening. Exposure of young VSMCs to phenylephrine in vitro increased Ang II protein and MMP2 activity to the levels of old VSMCs; Losartan abolished these effects. Thus, Ang Pi-induced effects on MMP2, transforming growth factor-beta 1, collagen, and VSMCs are central to the arterial remodeling that accompanies advancing age.