Schweitzer Morris, Mitmaker Benjamin, Obrand Daniel, Sheiner Nathan, Abraham Cherrie, Dostanic Stevan, Meilleur Melissa, Sugahara Tomoko, Chalifour Lorraine E
Department of Endocrinology, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec, Canada.
Vasc Endovascular Surg. 2010 Feb;44(2):116-22. doi: 10.1177/1538574409348352. Epub 2009 Dec 23.
Statins may reduce abdominal aortic aneurysm (AAA) progression. We sought to measure how atorvastatin (AT) treatment might modulate matrix metalloproteinase (MMP) expression and/or activity in human AAA. Tissue from human AAAs at surgical repair was obtained from patients who were either not on statins (NST, n = 19) or treated with AT (n = 19). Immunoblots measured expression and zymography measured activity. Expression of most proteins was greater in the central compared with distal AAA region. Matrix metalloproteinase 1, MMP2, MMP3, MMP9, Tissue Inhibitor of Metalloproteinase (TIMP2), TIMP3, TIMP4, or total Sma Mothers Against Decapentaplegia (SMAD2) expression did not differ with treatment. There was a trend toward reduced MMP8 and TIMP1 expression and MMP2 zymographic activity in the AT-treatment group. In contrast, AT-treated samples had significantly reduced MMP13 (P = .02), latent-transforming growth factor (TGF)-beta (P = .02), and phospho-SMAD2 (P = .029) expression than NST-treated samples. We conclude that the AT-mediated decrease in MMP expression and activity reduces TGF-beta signaling in the central region of human AAAs.
他汀类药物可能会减缓腹主动脉瘤（AAA）的进展。我们试图测定阿托伐他汀（AT）治疗如何调节人类AAA中基质金属蛋白酶（MMP）的表达和/或活性。手术修复时获取的人类AAA组织来自未服用他汀类药物的患者（非他汀类组，n = 19）或接受AT治疗的患者（n = 19）。免疫印迹法测定表达，酶谱法测定活性。与AAA远端区域相比，大多数蛋白质在中央区域的表达更高。MMP1、MMP2、MMP3、MMP9、金属蛋白酶组织抑制剂（TIMP2）、TIMP3、TIMP4或总抗SMAD2（SMAD2）的表达在治疗组间无差异。AT治疗组中MMP8和TIMP1的表达及MMP2酶谱活性有降低趋势。相比之下，与非他汀类治疗组样本相比，AT治疗组样本中MMP13（P = 0.02）、潜伏转化生长因子（TGF）-β（P = 0.02）和磷酸化SMAD2（P = 0.029）的表达显著降低。我们得出结论，AT介导的MMP表达和活性降低会减少人类AAA中央区域的TGF-β信号传导。
