Innate immunity and hypertension: unveiling inflammatory pathways for novel therapies

Abstract

Hypertension is a leading cause of global cardiovascular morbidity and mortality, yet its primary etiology remains poorly defined. Accumulating evidence increasingly positions inflammation as a key determinant of disease progression, with both innate and adaptive immune mechanisms playing central roles. Under physiological conditions, the immune system safeguards vascular homeostasis through the coordinated activity of immune cells and soluble mediators. Cells of the innate immune system, such as natural killer cells, dendritic cells, macrophages, and neutrophils, detect pathogen- and damage-associated molecular patterns via pattern recognition receptors, while complement proteins and antimicrobial peptides serve as additional effectors of host defense. Perturbations in these pathways, however, precipitate chronic inflammation that contributes to hypertensive pathology. Engagement of toll-like and nucleotide-binding oligomerization domain-like receptors initiates pro-inflammatory cascades that intensify oxidative stress, impair vasodilation, and compromise endothelial function. These alterations are further propagated by activated immune cells and by complement-mediated recruitment of leukocytes, which sustain a deleterious inflammatory milieu. Collectively, these mechanisms contribute to vascular injury and perpetuate elevated blood pressure. Emerging therapies designed to target these immune-inflammatory pathways offer promising opportunities to alleviate vascular dysfunction and ultimately transform the management of hypertension by addressing its immunological underpinnings.