Is NADPH oxidase the trigger for accelerated atherosclerosis caused by bacteria?

心血管疾病是全世界死亡和发病的主要原因。然而，其发病率并不能完全解释为存在传统的危险因素，如高胆固醇、高血压、糖尿病和吸烟。越来越多的证据表明，细菌感染，特别是肺炎衣原体和幽门螺杆菌感染，也与动脉粥样硬化病变形成和心血管事件风险增加密切相关。该项目将研究人体防御细菌感染的一个新方面，这涉及到血管壁产生氧自由基。我们认为，尽管动脉对血液中细菌的这种反应在短期内是有益的，但它无意中引发了慢性炎症过程，最终加速了动脉疾病的发展。如果是这样的话，在动脉壁上由NADPH氧化酶产生的氧自由基可能代表了细菌感染和动脉粥样硬化之间缺失的一环。因此，我们将首先测试肺炎衣原体和幽门螺杆菌两种细菌是否可以通过这种方式急性诱导动脉炎症。然后，我们将进行明确的研究，以测试感染这些细菌的小鼠是否会加速动脉粥样硬化，如果是，这种影响是否依赖于动脉壁中的NADPH氧化酶活性。最后，我们将测试抗生素治疗的有效性和重要性，以防止动脉粥样硬化病变的形成。

Cardiovascular disease is the leading cause of death and morbidity world-wide. However, its incidence is not fully explained by the presence of conventional risk factors, such as high cholesterol, hypertension, diabetes and cigarette smoking. Steadily growing evidence indicates that bacterial infection, particularly by Chlamydia pneumoniae and Helicobacter pylori, is also strongly linked to atherosclerotic lesion formation and increased risk of a cardiovascular event. This project will investigate a new aspect to the body s defence against bacterial infection which involves production of oxygen radicals by the blood vessel wall. We propose that although this response of the artery to bacteria in the blood is beneficial in the short term, it inadverently initiates a chronic inflammatory process that ultimately accelerates development of artery disease. If this is the case, the oxygen radical production by the enzyme, NADPH oxidase, in the artery wall may represent the missing link between bacterial infection and atherosclerosis. We will therefore firstly test whether two bacteria, Chlamydia pneumoniae and Helicobacter pylori, can acutely induce artery inflammation in this way. We will then perform definitive studies to test whether mice infected with these bacteria develop accelerated atherosclerosis, and if so, whether this effect is dependent on NADPH oxidase activity in the artery wall. Finally, we will test the efficacy and importance of timing of antibiotic therapy to prevent atherosclerotic lesion formation.