Nagashima Hirotaka, Uto Kento, Sakomura Yasunari, Aoka Yoshikazu, Sakuta Akiko, Aomi Shigeyuki, Hagiwara Nobuhisa, Kawana Masatoshi, Kasanuki Hiroshi
Department of Cardiology, The Heart Institute of Japan, Tokyo Women's Medical University, Tokyo, Japan.
J Vasc Surg. 2002 Oct;36(4):818-23.
Cystic medial degeneration (CMD) is a histologic abnormality that is common in aortic diseases such as aortic dilation, aneurysm, or dissection. Although little is known about the mechanism underlying CMD, we have previously demonstrated that angiotensin II signaling via angiotensin II type 2 receptor (AT2R) plays a central role in apoptosis of vascular smooth muscle cells (VSMCs) occurring in CMD associated with Marfan syndrome. The aim of this study is to elucidate the role of angiotensin II signaling in THE pathogenesis of aortic diseases associated with CMD.
We investigated the effects of angiotensin-converting enzyme inhibitor (ACEI), temocapril (n = 15), angiotensin II receptor type-1 (AT1R) blocker, CS-866 (n = 15), and vehicle control (n = 17) on 0.25% beta-aminopropionitrile monofumarate (BAPN)-induced aortic dissection and histopathologic findings in a rat model.
Temocapril significantly prevented aortic dissection (P <.05), CMD (P <.01), and VSMC apoptosis (P <.01) compared with vehicle control in BAPN-fed rats. However, CS-866 did not show any preventive effect. Reversed transcriptase-polymerase chain reaction demonstrated that expression of both AT1R and AT2R was detected in control rat aortas, and that AT2R expression was significantly upregulated in the aortas of BAPN-fed rats (P <.01). Blood pressure was significantly and equally lowered in both temocapril and CS-866 groups compared with control.
Differential expression of angiotensin II receptors and AT2R signaling are involved in the pathogenesis of CMD and aortic dissection in BAPN-fed rats. ACEIs might be of clinical value for the prevention and treatment of aortic diseases related to CMD.
囊性中层退变（CMD）是一种组织学异常，在主动脉扩张、动脉瘤或夹层等主动脉疾病中很常见。尽管对CMD的潜在机制了解甚少，但我们之前已经证明，通过血管紧张素II 2型受体（AT2R）的血管紧张素II信号在与马凡综合征相关的CMD中发生的血管平滑肌细胞（VSMC）凋亡中起核心作用。本研究的目的是阐明血管紧张素II信号在与CMD相关的主动脉疾病发病机制中的作用。
我们研究了血管紧张素转换酶抑制剂（ACEI）替莫卡普利（n = 15）、血管紧张素II 1型受体（AT1R）阻滞剂CS - 866（n = 15）和载体对照（n = 17）对0.25%单氟马尿酸β-氨基丙腈（BAPN）诱导的大鼠主动脉夹层和组织病理学结果的影响。
与BAPN喂养大鼠的载体对照相比，替莫卡普利显著预防了主动脉夹层（P <.05）、CMD（P <.01）和VSMC凋亡（P <.01）。然而，CS - 866没有显示出任何预防作用。逆转录聚合酶链反应表明，在对照大鼠主动脉中检测到AT1R和AT2R的表达，并且在BAPN喂养大鼠的主动脉中AT2R表达显著上调（P <.01）。与对照组相比，替莫卡普利组和CS - 866组的血压均显著且同等程度降低。
血管紧张素II受体和AT2R信号的差异表达参与了BAPN喂养大鼠CMD和主动脉夹层的发病机制。ACEI可能对预防和治疗与CMD相关的主动脉疾病具有临床价值。
