Xu Xinsheng, Lin Huili, Lv Huixia, Zhang Mei, Zhang Yun
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Shandong University Qilu Hospital, No.107, Wen Hua Xi Road, Jinan, Shandong 250012, China.
Med Hypotheses. 2007;69(6):1238-41. doi: 10.1016/j.mehy.2007.04.007. Epub 2007 Sep 6.
Arterial inflammation is a significant component of atherosclerotic disease-specific immune responses directed against autoantigens or pathogen-derived antigens in the vascular wall could initiate and/or maintain atherosclerotic processes. Atherosclerosis is now regarded as a chronic inflammatory disease. Developing in response to injury in the vessel wall, it is characterized by the infiltration of mononuclear lymphocytes into the intima, local expansion of vascular smooth muscle cells, and accumulation of extracellular matrix. A number of potential mechanisms have been implicated in the development of inflammatory reactions in the vascular system. Adventitia provides cells and molecules with the ability to influence neointimal formation and vascular remodeling implemented in part by vasa vasorum. We hypothesize that lymphatic vessels, existing in adventitia in the atherosclerotic artery, could drain local inflammatory cells and cytokines to the lymphatic nodes and lymphoid tissues where inflammatory cells can be sensitized and activated. Or, blood vessels may deliver sensitized inflammatory cells and cytokines to the inflammatory site of the vascular wall. Therefore, both lymphatic and blood vessels constitute a complete circle of immune response, whereby the inflammatory cells and cytokines are effectively delivered to tissues and their effects magnified. Under certain circumstances, this situation may lead to a vicious circle of inflammation such as in atherosclerosis, resulting in perpetuating intimal hyperplasia and vascular remodeling. Inhibition of lymphangiogenesis may interrupt this self-perpetuating vicious circle of inflammation in atherosclerosis and provide a new approach to the prevention and treatment of the disease.
动脉炎症是动脉粥样硬化疾病特异性免疫反应的重要组成部分,针对自身抗原或血管壁中病原体衍生抗原的免疫反应可启动和/或维持动脉粥样硬化进程。动脉粥样硬化现在被视为一种慢性炎症性疾病。它是对血管壁损伤的反应而发生的,其特征是单核淋巴细胞浸润到内膜、血管平滑肌细胞局部增生以及细胞外基质的积累。许多潜在机制与血管系统炎症反应的发展有关。外膜提供了能够影响新生内膜形成和血管重塑的细胞和分子,这部分是由滋养血管实现的。我们假设,存在于动脉粥样硬化动脉外膜中的淋巴管可以将局部炎症细胞和细胞因子引流到淋巴结和淋巴组织,在那里炎症细胞可以被致敏和激活。或者,血管可能将致敏的炎症细胞和细胞因子输送到血管壁的炎症部位。因此,淋巴管和血管都构成了一个完整的免疫反应循环,由此炎症细胞和细胞因子被有效地输送到组织中,其作用被放大。在某些情况下,这种情况可能导致炎症的恶性循环,如在动脉粥样硬化中,导致内膜增生和血管重塑持续存在。抑制淋巴管生成可能会中断动脉粥样硬化中这种自我持续的炎症恶性循环,并为该疾病的预防和治疗提供一种新方法。