Hypertension Research Laboratory, School of Biological Sciences, Monash University, Melbourne, VIC, Australia; Victorian Heart Institute, Monash University, Clayton, Australia.
Hypertension Research Laboratory, School of Biological Sciences, Monash University, Melbourne, VIC, Australia; Heart Failure Research Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia; Victorian Heart Institute, Monash University, Clayton, Australia.
Eur J Pharmacol. 2024 Nov 15;983:177008. doi: 10.1016/j.ejphar.2024.177008. Epub 2024 Sep 18.
Hypertension is the key leading risk factor for death globally, affecting ∼1.3 billion adults, particularly in low- and middle-income countries. Most people living with hypertension have uncontrolled high blood pressure, increasing their likelihood of cardiovascular events. Significant issues preventing blood pressure control include lack of diagnosis, treatment, and response to existing therapy. For example, monotherapy and combination therapy are often unable to lower blood pressure to target levels. New therapies are urgently required to tackle this issue, particularly those that target the mechanisms behind hypertension instead of treating its symptoms. Acting via an increase in systemic and tissue-specific inflammation, the immune system is a critical contributor to blood pressure regulation and is considered an early mechanism leading to hypertension development. Here, we review the immune system's role in hypertension, evaluate clinical trials that target inflammation, and discuss knowledge gaps in pre-clinical and clinical data. We examine the effects of anti-inflammatory drugs colchicine and methotrexate on hypertension and evaluate the blockade of pro-inflammatory cytokines IL-1β and TNF-α on blood pressure in clinical trials. Lastly, we highlight how we can move forward to target specific components of the immune system to lower blood pressure. This includes targeting isolevuglandins, which accumulate in dendritic cells to promote T cell activation and cytokine production in salt-induced hypertension. We discuss the potential of the dietary fibre-derived metabolites short-chain fatty acids, which have anti-inflammatory and blood pressure-lowering effects via the gut microbiome. This would limit adverse events, leading to improved medication adherence and better blood pressure control.
高血压是全球导致死亡的主要危险因素，影响着约 13 亿成年人，尤其是在中低收入国家。大多数高血压患者的血压得不到控制，增加了他们发生心血管事件的可能性。导致血压控制不理想的主要问题包括诊断不足、治疗不足以及对现有治疗方案的反应不足。例如，单药治疗和联合治疗通常无法将血压降至目标水平。迫切需要新的治疗方法来解决这个问题，特别是那些针对高血压背后机制而不是治疗其症状的治疗方法。免疫系统通过增加全身和组织特异性炎症来发挥作用，是血压调节的关键贡献者，被认为是导致高血压发展的早期机制。在这里，我们回顾了免疫系统在高血压中的作用，评估了针对炎症的临床试验，并讨论了临床前和临床数据中的知识空白。我们研究了抗炎药物秋水仙碱和甲氨蝶呤对高血压的影响，并评估了临床试验中抑制促炎细胞因子 IL-1β 和 TNF-α 对血压的影响。最后，我们强调了如何针对免疫系统的特定成分来降低血压。这包括针对异亮氨酸衍生的类异戊二烯，它们在盐诱导的高血压中在树突状细胞中积累，以促进 T 细胞激活和细胞因子产生。我们还讨论了膳食纤维衍生代谢物短链脂肪酸的潜力，它们通过肠道微生物群发挥抗炎和降压作用。这将限制不良反应的发生，提高药物的依从性，更好地控制血压。
