Inhibiting C-reactive protein for the treatment of cardiovascular disease: promising evidence from rodent models.
Inhibiting C-reactive protein for the treatment of cardiovascular disease: promising evidence from rodent models.
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DOI：
10.1155/2014/353614
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发表时间：
2014
影响因子：
4.6
通讯作者：
Crooke RM
中科院分区：
文献类型：
--
作者：
Szalai AJ;McCrory MA;Xing D;Hage FG;Miller A;Oparil S;Chen YF;Mazzone M;Early R;Henry SP;Zanardi TA;Graham MJ;Crooke RM
血C反应蛋白(CRP)水平升高是心血管事件的预测指标，但血CRP在疾病过程中是否是因果关系尚不清楚。在随机病例对照研究的背景下，通过对蛋白质的药理抑制来定义后者是最好的。然而，目前还没有专门针对CRP的药物，因此这样的前瞻性研究不能进行。血中的CRP主要在肝脏中合成，肝脏是反义寡核苷酸(ASO)药物积累的器官。利用这一点，我们评估了CRP特异性ASO在实验诱导的心血管损伤的啮齿动物中的疗效。用大鼠C反应蛋白特异性ASO治疗4周后，血C反应蛋白降低了60%。值得注意的是，这种效应与心肌梗死(结扎左前降支引起的)后心功能和病理的改善有关。同样，在用人CRP特异性ASO治疗2周的人CRP转基因小鼠中，血液中的人CRP降低了70%，颈动脉通畅性得到改善(手术结扎后2周)。CRP特异性ASO可能为一项安慰剂对照试验铺平道路，该试验可以阐明CRP在心血管疾病中的作用。
Raised blood C-reactive protein (CRP) level is a predictor of cardiovascular events, but whether blood CRP is causal in the disease process is unknown. The latter would best be defined by pharmacological inhibition of the protein in the context of a randomized case-control study. However, no CRP specific drug is currently available so such a prospective study cannot be performed. Blood CRP is synthesized primarily in the liver and the liver is an organ where antisense oligonucleotide (ASO) drugs accumulate. Taking advantage of this we evaluated the efficacy of CRP specific ASOs in rodents with experimentally induced cardiovascular damage. Treating rats for 4 weeks with a rat CRP-specific ASO achieved >60% reduction of blood CRP. Notably, this effect was associated with improved heart function and pathology following myocardial infarction (induced by ligation of the left anterior descending artery). Likewise in human CRP transgenic mice treated for 2 weeks with a human CRP-specific ASO, blood human CRP was reduced by >70% and carotid artery patency was improved (2 weeks after surgical ligation). CRP specific ASOs might pave the way towards a placebo-controlled trial that could clarify the role of CRP in cardiovascular disease.
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DOI：
10.1161/atvbaha.110.205377
发表时间：
2010-06
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Hage FG;Oparil S;Xing D;Chen YF;McCrory MA;Szalai AJ
通讯作者：
Szalai AJ
影响因子：
3.4
作者：
Meuwissen, M;van der Wal, AC;Piek, JJ
通讯作者：
Piek, JJ
影响因子：
2.8
作者：
Haffner, SM
通讯作者：
Haffner, SM
DOI：
10.1161/01.atv.19.10.2348
发表时间：
1999-10-01
影响因子：
8.7
作者：
Bhakdi, S;Torzewski, M;Hemmes, M
通讯作者：
Hemmes, M
DOI：
10.1155/2013/379040
发表时间：
2013-09-14
期刊：
ISRN inflammation
影响因子：
--
作者：
Du Clos TW
通讯作者：
Du Clos TW