مقاله انگلیسی رایگان در مورد هدف گیری سیستم ایمنی برای درمان فشارخون بالا – الزویر ۲۰۲۴

Abstract

Hypertension is the key leading risk factor for death globally, affecting ∼۱٫۳ 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.

Targeting the immune system in hypertension through diet and gut microbiome

The gut microbiome (all microbes including bacteria, viruses, fungal, and their genes) (Berg et al., 2020) has emerged as a contributing factor to many health states and diseases (Vos et al., 2022), including hypertension (O’Donnell et al., 2023). The gastrointestinal tract not only harbours the largest collection of microbes compared to other sites in the human body, but also houses the largest compartment of immune cells (Mowat and Agace, 2014). It is, therefore, reasonable that the gut microbiome influences the immune system, and vice-versa (Zheng et al., 2020). These two compartments are separated only by a single layer of cells, primarily epithelial but also Goblet cells and other cell types, which actively produce substances such as mucus to maintain the barrier between the microbes and the host (Snelson et al., 2024). In addition to a physical and chemical barrier, both compartments affect the barrier by affecting tight junctions between the cells (Schreiber et al., 2024). Epithelial cells also express many different receptors to metabolites produced by the gut microbiota, some pro- and others anti-inflammatory (Didriksen et al., 2024; Ghosh et al., 2021; Kim, 2023). These gut microbiota-derived metabolites have been extensively studied in the past decade, but importantly, they influence many facets of physiology, including the immune system (Yang and Cong, 2021; Zheng et al., 2020). The absence of the gut microbiome results in impaired immune function, supporting the fact that the gut microbiome is required for the maturation and maintenance of the immune system (Fiebiger et al., 2016; Round and Mazmanian, 2009).

Conclusion

To effectively lower hypertension rates globally, new treatments are urgently required. Dampening immune system activation and inflammation in targeted patient groups may be an effective way to control BP. A greater understanding of how the immune system is triggered in different patient subgroups is required to facilitate a personalised medicine approach, which may be needed to determine which treatment would likely yield the best results.