Mechanisms of oxidative stress in human aortic aneurysms--association with clinical risk factors for atherosclerosis and disease severity.
Mechanisms of oxidative stress in human aortic aneurysms--association with clinical risk factors for atherosclerosis and disease severity.
复制标题
DOI：
10.1016/j.ijcard.2013.01.278
复制
发表时间：
2013-10-03
影响因子：
3.5
通讯作者：
Guzik, Tomasz J.
中科院分区：
文献类型：
--
作者：
Guzik, Bartlomiej;Sagan, Agnieszka;Ludew, Dominik;Mrowiecki, Wojciech;Chwala, Maciej;Bujak-Gizycka, Beata;Filip, Grzegorz;Grudzien, Grzegorz;Kapelak, Boguslaw;Zmudka, Krzysztof;Mrowiecki, Tomasz;Sadowski, Jerzy;Korbut, Ryszard;Guzik, Tomasz J.
关键词：
腹主动脉瘤（AAA）是心血管疾病发病和死亡的重要原因。氧化应激可能与 AAA 的多种机制有关，包括血管炎症和金属蛋白酶活性增加。然而，血管自由基产生的机制仍不清楚。因此，我们的目的是确定人类 AAA 中血管超氧化物 (O2•−) 产生的来源和分子调控。从 40 名接受 AAA 修复的受试者中获取 AAA 节段和匹配的非扩张主动脉样本。 AAA 受试者 (n = 16) 血浆中的 MDA 水平（通过 HPLC/MS 测定）高于危险因素匹配的对照组 (n = 16)。同样，通过光泽精化学发光和二氢乙锭荧光测量，与非扩张的主动脉标本相比，动脉瘤部分的超氧化物产生增加。 NADPH 氧化酶和 iNOS 是 AAA 中 O2•− 的主要来源。黄嘌呤氧化酶、线粒体氧化酶和环氧合酶抑制作用较小或没有作用。抑制蛋白激酶 C 对 AAA 中超氧化物的产生没有影响。 AAA 中 p22phox、nox2 和 nox5 的 NADPH 氧化酶亚基 mRNA 水平显着增加，而 nox4 mRNA 表达较低。 AAA 修复风险 Vanzetto 评分增加的受试者中超氧化物的产生较高，并且与 AAA 队列中吸烟、高胆固醇血症和 CAD 的存在显着相关。基础超氧化物产生和 NADPH 氧化酶活性与动脉瘤大小相关。 NADPH 氧化酶的表达和活性增加是人腹主动脉瘤氧化应激的重要机制。未偶联的 iNOS 可能将氧化应激与 AAA 中的炎症联系起来。氧化应激与 AAA 患者的动脉瘤大小和主要临床危险因素有关。
Aortic abdominal aneurysms (AAA) are important causes of cardiovascular morbidity and mortality. Oxidative stress may link multiple mechanisms of AAA including vascular inflammation and increased metalloproteinase activity. However, the mechanisms of vascular free radical production remain unknown. Accordingly, we aimed to determine sources and molecular regulation of vascular superoxide (O2•−) production in human AAA. AAA segments and matched non-dilated aortic samples were obtained from 40 subjects undergoing AAA repair. MDA levels (determined by HPLC/MS) were greater in plasma of AAA subjects (n = 16) than in risk factor matched controls (n = 16). Similarly, superoxide production, measured by lucigenin chemiluminescence and dihydroethidium fluorescence, was increased in aneurysmatic segments compared to non-dilated aortic specimens. NADPH oxidases and iNOS are the primary sources of O2•− in AAA. Xanthine oxidase, mitochondrial oxidases and cyclooxygenase inhibition had minor or no effect. Protein kinase C inhibition had no effect on superoxide production in AAA. NADPH oxidase subunit mRNA levels for p22phox, nox2 and nox5 were significantly increased in AAAs while nox4 mRNA expression was lower. Superoxide production was higher in subjects with increased AAA repair risk Vanzetto score and was significantly associated with smoking, hypercholesterolemia and presence of CAD in AAA cohort. Basal superoxide production and NADPH oxidase activity were correlated to aneurysm size. Increased expression and activity of NADPH oxidases are important mechanisms underlying oxidative stress in human aortic abdominal aneurysm. Uncoupled iNOS may link oxidative stress to inflammation in AAA. Oxidative stress is related to aneurysm size and major clinical risk factors in AAA patients.
登录
查看更多内容
影响因子：
20.1
作者：
Guzik, TJ;West, NEJ;Channon, KM
通讯作者：
Channon, KM
DOI：
10.1161/hypertensionaha.109.142646
发表时间：
2010-02
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Lob HE;Marvar PJ;Guzik TJ;Sharma S;McCann LA;Weyand C;Gordon FJ;Harrison DG
通讯作者：
Harrison DG
影响因子：
37.8
作者：
Guzik, TJ;Mussa, S;Channon, KM
通讯作者：
Channon, KM
DOI：
10.1016/j.ejvs.2004.02.010
发表时间：
2004-07-01
影响因子：
5.7
作者：
Nesi, F;Leo, E;Juvonen, T
通讯作者：
Juvonen, T
影响因子：
37.8
作者：
Antoniades C;Bakogiannis C;Leeson P;Guzik TJ;Zhang MH;Tousoulis D;Antonopoulos AS;Demosthenous M;Marinou K;Hale A;Paschalis A;Psarros C;Triantafyllou C;Bendall J;Casadei B;Stefanadis C;Channon KM
通讯作者：
Channon KM