van den Berg Carmen W, Taylor Karolina E, Lang Derek
Department of Pharmacology, Therapeutics, and Toxicology, Wales Heart Research Institute, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, United Kingdom.
Arterioscler Thromb Vasc Biol. 2004 Oct;24(10):e168-71. doi: 10.1161/01.ATV.0000142807.92781.d9. Epub 2004 Aug 19.
Although C-reactive protein (CRP) is increasingly recognized as an independent risk factor for acute myocardial events, recent evidence suggests that it can directly induce vasorelaxation. This study aimed to investigate the mechanism of this CRP-induced response.
Isometric tension recordings were used to measure endothelium-dependent and endothelium-independent vascular smooth muscle relaxation in isolated rabbit aortic rings. CRP generated in-house by genetic engineering and expressed in Chinese hamster ovary cells, CRP purified from ascites, and CRP obtained from commercial sources were assessed for vasorelaxing properties. Only the commercial CRP preparation induced vasorelaxation; more than half maximal relaxation was observed at 0.025 microg/mL and maximum relaxation attained at 0.25 microg/mL. Commercial CRP contains high levels of sodium azide, a well-known vasorelaxant. Removal of this agent by dialysis abolished the vasodilatory effect of commercial CRP. Sodium azide alone at concentrations equivalent to that present in the commercial CRP produced a near-identical relaxation pattern to the undialyzed commercial product.
CRP has no vasorelaxant properties per se, and the reported vasorelaxant ability of CRP is an artifact caused by sodium azide present in commercial preparations of this agent.
尽管C反应蛋白(CRP)日益被认为是急性心肌事件的独立危险因素,但最近有证据表明它可直接诱导血管舒张。本研究旨在探讨这种CRP诱导反应的机制。
采用等长张力记录法测量离体兔主动脉环中内皮依赖性和非内皮依赖性血管平滑肌舒张情况。对通过基因工程在内部生成并在中国仓鼠卵巢细胞中表达的CRP、从腹水中纯化的CRP以及从商业来源获得的CRP进行血管舒张特性评估。只有商业CRP制剂能诱导血管舒张;在0.025微克/毫升时观察到超过半数最大舒张,在0.25微克/毫升时达到最大舒张。商业CRP含有高水平的叠氮化钠,一种众所周知的血管舒张剂。通过透析去除该试剂可消除商业CRP的血管舒张作用。单独的叠氮化钠在与商业CRP中存在的浓度相当的情况下产生与未透析的商业产品几乎相同的舒张模式。
CRP本身不具有血管舒张特性,所报道的CRP的血管舒张能力是该试剂商业制剂中存在的叠氮化钠导致的假象。