Arterial and cardiac aging: Major shareholders in cardiovascular disease enterprises - Part III: Cellular and molecular clues to heart and arterial aging
Arterial and cardiac aging: Major shareholders in cardiovascular disease enterprises - Part III: Cellular and molecular clues to heart and arterial aging
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DOI：
10.1161/01.cir.0000048894.99865.02
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发表时间：
2003-01-28
期刊：
影响因子：
37.8
通讯作者：
Lakatta, EG
中科院分区：
文献类型：
--
作者：
Lakatta, EG
大鼠颈动脉球囊损伤后，可以通过切割早期生长反应基因Egr-1的mRNA来防止过度的内膜形成，Egr-1是一种锌指转录因子，可调节一系列应激反应基因，包括影响细胞增殖、迁移和凋亡的PDGF和TGF-。尽管tgf的抗增殖作用随着年龄的增长而减弱，但tgf可以抑制蛋白酶的活性，激活MMP的组织抑制剂，并且是细胞外基质蛋白合成的一个有效因素。因此，tgf表达的增加可以促进基质的形成。老年大鼠内膜中tgf的积累可能与动脉纤维连接蛋白和胶原蛋白的年龄相关增加有关。4,20纤维连接蛋白和tgf的表达均受血管紧张素II的调控。在大鼠和非人灵长类动物中，主动脉血管紧张素转换酶（ACE）活性与年龄相关的增加也存在；主动脉血管紧张素II升高，并与ACE和MMP-2升高共定位。23重要的是，许多与年龄相关的内膜和基质变化可以通过长期服用ACE抑制剂而明显延迟，3表明局部血管紧张素系统的年龄相关变化可能在与年龄相关的血管重构中起核心作用。
Excessive neointimal formation observed after balloon injury to the rat carotid artery can be prevented by cleaving the mRNA of the early growth response gene, Egr-1, a zinc-finger transcription factor that modulates a host of stress-responsive genes, including PDGF and TGF-, which impact cellular proliferation, migration, and apoptosis. 18 Although the antiproliferative actions of TGF-decrease with age, 19 TGF-suppresses the activity of proteases, activates tissue inhibitors of MMP, and is a potent factor for the synthesis of extracellular matrix proteins. An increase in the expression of TGF-can therefore promote matrix formation. TGF-accumulation in the intima of older rats may be related to the age-associated increase in arterial fibronectin and collagen. 4, 20 Fibronectin and TGF-expression are both regulated by angiotensin II. 21 An age-associated increase in aortic angiotensin converting enzyme (ACE) activity occurs in rats22 and nonhuman primates; aortic angiotensin II is increased and co-localizes with both increased ACE and MMP-2. 23 Importantly, many of the age-associated intimal and matrix changes can be markedly delayed by chronic administration of ACE inhibitors, 3 suggesting that ageassociated changes in the local vascular angiotensin system may play a central role in age-associated vascular remodeling.