Division of Clinical Pharmacology (M.S.M., F.E., M.R.A., A.P., J.I., J.P.V.B., D.M.P., C.D.S., C.L.L., A.K.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Division of Cardiovascular Medicine (M.S.M., M.R.A., D.M.P.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Circ Res. 2021 Apr 2;128(7):908-933. doi: 10.1161/CIRCRESAHA.121.318052. Epub 2021 Apr 1.
Elevated cardiovascular risk including stroke, heart failure, and heart attack is present even after normalization of blood pressure in patients with hypertension. Underlying immune cell activation is a likely culprit. Although immune cells are important for protection against invading pathogens, their chronic overactivation may lead to tissue damage and high blood pressure. Triggers that may initiate immune activation include viral infections, autoimmunity, and lifestyle factors such as excess dietary salt. These conditions activate the immune system either directly or through their impact on the gut microbiome, which ultimately produces chronic inflammation and hypertension. T cells are central to the immune responses contributing to hypertension. They are activated in part by binding specific antigens that are presented in major histocompatibility complex molecules on professional antigen-presenting cells, and they generate repertoires of rearranged T-cell receptors. Activated T cells infiltrate tissues and produce cytokines including interleukin 17A, which promote renal and vascular dysfunction and end-organ damage leading to hypertension. In this comprehensive review, we highlight environmental, genetic, and microbial associated mechanisms contributing to both innate and adaptive immune cell activation leading to hypertension. Targeting the underlying chronic immune cell activation in hypertension has the potential to mitigate the excess cardiovascular risk associated with this common and deadly disease.
高血压患者的血压即使恢复正常,心血管疾病风险(包括中风、心力衰竭和心脏病发作)仍然较高。潜在的免疫细胞激活是一个可能的罪魁祸首。虽然免疫细胞对于抵御入侵病原体很重要,但它们的慢性过度激活可能导致组织损伤和高血压。可能引发免疫激活的触发因素包括病毒感染、自身免疫和生活方式因素,如过量的膳食盐。这些情况要么直接激活免疫系统,要么通过它们对肠道微生物组的影响激活免疫系统,最终导致慢性炎症和高血压。T 细胞是导致高血压的免疫反应的核心。它们的部分激活是通过与主要组织相容性复合物分子上呈现的特定抗原结合来实现的,并且它们产生了重组 T 细胞受体的库。激活的 T 细胞浸润组织并产生细胞因子,包括白细胞介素 17A,这会促进肾脏和血管功能障碍以及终末器官损伤,导致高血压。在这篇全面的综述中,我们强调了导致高血压的固有和适应性免疫细胞激活的环境、遗传和微生物相关机制。针对高血压中潜在的慢性免疫细胞激活具有减轻与这种常见且致命疾病相关的过度心血管风险的潜力。