Group X secretory phospholipase A(2) augments angiotensin II-induced inflammatory responses and abdominal aortic aneurysm formation in apoE-deficient mice.
Group X secretory phospholipase A(2) augments angiotensin II-induced inflammatory responses and abdominal aortic aneurysm formation in apoE-deficient mice.
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DOI：
10.1016/j.atherosclerosis.2010.08.054
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发表时间：
2011-01
期刊：
影响因子：
5.3
通讯作者：
Webb, Nancy R.
中科院分区：
文献类型：
--
作者：
Zack, Melissa;Boyanovsky, Boris B.;Shridas, Preetha;Bailey, William;Forrest, Kathy;Howatt, Deborah A.;Gelb, Michael H.;de Beer, Frederick C.;Daugherty, Alan;Webb, Nancy R.
腹主动脉瘤（AAA）是一种复杂的血管疾病，其特征是基质降解和炎症，是老年男性死亡的主要原因。预防 AAA 进展的具体干预措施仍有待确定。在这项研究中，我们测试了 X 组分泌性磷脂酶 A2 (GX sPLA2)（一种与炎症过程有关的酶）介导 AAA 的假设。通过人类动脉瘤组织和载脂蛋白 E 缺陷 (apoE−/−) 小鼠血管紧张素 II (Ang II) 诱导的 AAA 中的免疫染色检测到 GX sPLA2。响应 Ang II 输注，apoE−/− 小鼠腹主动脉中 GX sPLA2 mRNA 显着增加（11 倍）。为了确定 GX sPLA2 在实验性 AAA 中的作用，apoE−/− 和 apoE−/− × GX sPLA2−/− (GX DKO) 小鼠被注射 Ang II 10 (n=7) 或 28 (n=24–26) 天。通过主动脉腔体内超声测量和体外外径计算机辅助形态测量分析评估，GX sPLA2 缺乏显着降低了 AAA 的发生率和严重程度。基因表达谱结果表明，与 apoE−/− 小鼠相比，在 Ang II 输注 10 天后，GX DKO 小鼠主动脉中特定基质金属蛋白酶和炎症介质的表达减弱。与 apoE−/− 小鼠相比，GX DKO 小鼠中 Ang II 对环氧合酶-2、白介素-6、基质金属蛋白酶 (MMP)-2、MMP-13 和 MMP-14 的诱导显着降低。 GX sPLA2 促进 Ang II 诱导的病理反应，导致 AAA 形成。
Abdominal aortic aneurysm (AAA) is a complex vascular disease characterized by matrix degradation and inflammation and is a major cause of mortality in older men. Specific interventions that prevent AAA progression remain to be identified. In this study, we tested the hypothesis that Group X secretory phospholipase A2 (GX sPLA2), an enzyme implicated in inflammatory processes, mediates AAA. GX sPLA2 was detected by immunostaining in human aneurysmal tissue and in angiotensin II (Ang II)-induced AAAs in apolipoprotein E-deficient (apoE−/−) mice. GX sPLA2 mRNA was increased significantly (11-fold) in abdominal aortas of apoE−/− mice in response to Ang II infusion. To define the role of GX sPLA2 in experimental AAAs, apoE−/− and apoE−/− × GX sPLA2−/− (GX DKO) mice were infused with Ang II for either 10 (n=7) or 28 (n=24–26) days. Deficiency of GX sPLA2 significantly reduced the incidence and severity of AAAs, as assessed by ultrasound measurements in vivo of aortic lumens and by computer-assisted morphometric analyses ex vivo of external diameter. Results from gene expression profiling indicated that the expression of specific matrix metalloproteinases and inflammatory mediators was blunted in aortas from GX DKO mice compared to apoE−/− mice after 10-day Ang II infusion. Ang II induction of cyclooxygenase-2, interleukin-6, matrix metalloproteinase (MMP)-2, MMP-13 and MMP-14 was reduced significantly in GX DKO mice compared to apoE−/− mice. GX sPLA2 promotes Ang II-induced pathological responses leading to AAA formation.
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DOI：
10.1111/j.1749-6632.1999.tb07789.x
发表时间：
1999-01-01
期刊：
THE METABOLIC SYNDROME X
影响因子：
--
作者：
Daugherty, A;Cassis, L
通讯作者：
Cassis, L
影响因子：
3.4
作者：
Rosenson, Robert S.
通讯作者：
Rosenson, Robert S.
DOI：
10.1161/atvbaha.107.155564
发表时间：
2008-04-01
影响因子：
8.7
作者：
Jones, Gregory T.;Thompson, Andrew R.;van Rij, Andre M.
通讯作者：
van Rij, Andre M.
影响因子：
4.4
作者：
Granata, F;Petraroli, A;Triggiani, M
通讯作者：
Triggiani, M
影响因子：
15.9
作者：
Qi, ZH;Hao, CM;Breyer, MD
通讯作者：
Breyer, MD