Abstract

Vascular endothelial dysfunction (ED) forms the cornerstone in the development of atherosclerotic lesions that clinically manifest as ischemia, myocardial infarction, stroke or peripheral arterial disease. ED can be triggered by various risk factors including hypercholesterolemia, hypertension, hyperhomocystenemia and chronic low-grade inflammation. These risk factors also activate immune response systemically. Current drugs used for managing atherosclerosis not only aid in subsiding the risk factor but also suppress the immune activation. Nonetheless, their effectiveness in treating ED is still questionable. Here, we discuss how pathologic molecules and processes pertaining to ED can activate innate and adaptive arms of the immune system leading to disease progression even in the absence of cardiovascular risk factors and the potential of the current drugs, used in the management of atherosclerotic patients, in reversing them. We mainly focus on activated endothelium, endothelial microparticles, mechanically stretched endothelial cells, endothelial mesenchymal transition and endothelial glycocalyx sheds.

摘要

血管内皮功能障碍 (ED) 是动脉粥样硬化病变发展的基石，临床表现为缺血、心肌梗塞、中风或外周动脉疾病。ED可由各种危险因素引发，包括高胆固醇血症、高血压、高同型半胱氨酸血症和慢性低度炎症。这些风险因素也会系统性地激活免疫反应。目前用于治疗动脉粥样硬化的药物不仅有助于降低风险因素，还可以抑制免疫激活。尽管如此，它们在治疗 ED 方面的有效性仍然值得怀疑。这里，我们讨论了与 ED 相关的病理分子和过程如何激活免疫系统的先天性和适应性臂，导致疾病进展，即使在没有心血管危险因素的情况下，以及当前用于治疗动脉粥样硬化患者的药物的潜力，在逆转他们。我们主要关注活化的内皮、内皮微粒、机械拉伸的内皮细胞、内皮间质转化和内皮糖萼脱落。