Polyzos K A, Ketelhuth D F J
Dr. Daniel F. J. Ketelhuth, Cardiovascular Research Unit, Center for Molecular Medicine, L8:03, Karolinska University Hospital, S-17176 Stockholm, Sweden, Fax +46/8/31 31 47, E-mail:
Hamostaseologie. 2015;35(2):128-36. doi: 10.5482/HAMO-14-10-0052. Epub 2015 Jan 19.
Coronary heart disease and stroke, the deadliest forms of cardiovascular disease (CVD), are mainly caused by atherosclerosis, a chronic inflammatory disease of the artery wall driven by maladaptive immune responses in the vessel wall. Various risk factors for CVD influence this pathogenic process, including diabetes mellitus, hypertension, dyslipidaemia, and obesity. Indoleamine 2,3-dioxygenase (IDO), an enzyme catalyzing the rate-limiting step in the kynurenine pathway of tryptophan degradation, is strongly induced by inflammation in several tissues, including the artery wall. An increasing body of evidence indicates that IDO promotes immune tolerance, decreases inflammation, and functions as a homeostatic mechanism against excessive immune reactions. This review provides an overview of the emerging field of the kynurenine pathway of tryptophan degradation in CVD, emphasizing the role of IDO-mediated tryptophan metabolism and its metabolites in the modulation of 'classical' cardiovascular risk factors, such as hypertension, obesity, lipid metabolism, diabetes mellitus, and in the development of atherosclerotic CVD.
冠心病和中风是心血管疾病（CVD）最致命的形式，主要由动脉粥样硬化引起，动脉粥样硬化是一种由血管壁中适应性免疫反应驱动的动脉壁慢性炎症性疾病。心血管疾病的各种危险因素会影响这一致病过程，包括糖尿病、高血压、血脂异常和肥胖。吲哚胺2,3-双加氧酶（IDO）是一种催化色氨酸降解犬尿氨酸途径限速步骤的酶，在包括动脉壁在内的多种组织中会被炎症强烈诱导。越来越多的证据表明，IDO可促进免疫耐受、减轻炎症，并作为一种对抗过度免疫反应的稳态机制发挥作用。本综述概述了色氨酸降解犬尿氨酸途径在心血管疾病这一新兴领域的研究情况，着重阐述了IDO介导的色氨酸代谢及其代谢产物在调节“经典”心血管危险因素（如高血压、肥胖、脂质代谢、糖尿病）以及动脉粥样硬化性心血管疾病发展过程中的作用。
