Immune mechanisms in the pathophysiology of hypertension

Hypertension is a leading risk factor for morbidity and mortality worldwide. Despite current anti-hypertensive therapies, most individuals with hypertension fail to achieve adequate blood pressure control. Moreover, even with adequate control, a residual risk of cardiovascular events and associated organ damage remains. These findings suggest that current treatment modalities are not addressing a key element of the underlying pathology. Emerging evidence implicates immune cells as key mediators in the development and progression of hypertension. In this Review, we discuss our current understanding of the diverse roles of innate and adaptive immune cells in hypertension, highlighting key findings from human and rodent studies. We explore mechanisms by which these immune cells promote hypertensive pathophysiology, shedding light on their multifaceted involvement. In addition, we highlight advances in our understanding of autoimmunity, HIV and immune checkpoints that provide valuable insight into mechanisms of chronic and dysregulated inflammation in hypertension. This Review outlines the roles of innate and adaptive immune cells in hypertension. The authors discuss the mechanisms and important properties of immune cells that contribute to hypertension pathogenesis, such as memory and plasticity. Emerging evidence from human and rodent studies suggests an important role for both innate and adaptive immune cells in the pathogenesis of hypertension.The release of inflammatory cytokines, production of reactive oxygen species, and neoantigen presentation by innate immune cells results in vascular damage, renal injury, inflammation and elevated blood pressure.Adaptive immune cells shift towards pro-inflammatory roles in hypertension, resulting in enhanced cytotoxicity and inflammatory cytokine production that leads to impaired vascular and renal natriuretic functions.Immune cells coordinate as an integrated system, suggesting that targeting regulatory nodes of the inflammatory response might be beneficial for treating hypertension.Current evidence supports a model whereby immune activation and resultant hypertension-related organ dysfunction act synergistically to amplify blood pressure and promote end-organ damage in hypertension.Advances in our understanding of autoimmunity, HIV and immune checkpoint inhibitor therapies provide key insights into the effects of immune activation and chronic inflammation in the development of hypertension.