Department of Endocrinology, Sir Mortimer B. Davis-Jewish General Hospital, 3755 chemin Côte Ste Catherine, Montréal, QC H3T 1E2, Canada.
Can J Physiol Pharmacol. 2009 Nov;87(11):915-22. doi: 10.1139/y09-085.
Chronic apoptosis activation may participate in abdominal aortic aneurysm (AAA) expansion. Statin treatment slows AAA progression independent of cholesterol lowering. We hypothesized that Atorvastatin treatment alters apoptosis protein expression and activation in AAAs. Protein was isolated from the central and distal portions of end-stage human AAA tissue obtained during surgical repair from non-statin (NST) and Atorvastatin-treated (AT) patients. Expression was compared using immunoblots. Bcl-2 expression was unchanged but Bak (4-fold, p < 0.013) and Bax (3-fold, p < 0.035) expression was increased in AT (n = 12) versus NST (n = 15) patients. No cytochrome c release or caspase 3 activation was detected and Clusterin, GRP78, and BNIP1 expression was similar in NST and AT samples. Bcl-2 and Bax cDNA sequences from AAA tissue (n = 10) and the general population were identical. Thus, the increase in Bax and Bak in AT-treated AAAs did not activate the mitochondria or endoplasmic reticulum mediated apoptosis pathways. Bcl-2, Bax, and Bak have non-apoptosis related functions that include maintenance of endoplasmic reticulum (ER), homeostasis, and adaptation to stress. We speculate that Atorvastatin-mediated increases in Bax and Bak may positively affect their non-apoptosis related cell functions to account for the beneficial effect of statins to slow AAA expansion.
慢性细胞凋亡激活可能参与腹主动脉瘤（AAA）的扩张。他汀类药物治疗可减缓 AAA 的进展，而不依赖于降低胆固醇。我们假设阿托伐他汀治疗可改变 AAA 中凋亡蛋白的表达和激活。从接受他汀类药物（AT）治疗和未接受他汀类药物（NST）治疗的患者的外科修复术中获得终末期人 AAA 组织的中央和远端部分分离出蛋白质。使用免疫印迹比较表达。Bcl-2 的表达保持不变，但 Bak（4 倍，p < 0.013）和 Bax（3 倍，p < 0.035）的表达在 AT（n = 12）患者中高于 NST（n = 15）患者。未检测到细胞色素 c 释放或 caspase 3 激活，NST 和 AT 样本中的 Clusterin、GRP78 和 BNIP1 表达相似。从 AAA 组织（n = 10）和普通人群中分离出的 Bcl-2 和 Bax cDNA 序列相同。因此，AT 治疗的 AAA 中 Bax 和 Bak 的增加并未激活线粒体或内质网介导的细胞凋亡途径。Bcl-2、Bax 和 Bak 具有非凋亡相关的功能，包括维持内质网（ER）、体内平衡和适应应激。我们推测，阿托伐他汀介导的 Bax 和 Bak 增加可能会对其非凋亡相关的细胞功能产生积极影响，从而解释他汀类药物减缓 AAA 扩张的有益作用。
