The role of inflammation in hypertension: novel concepts

Abstract

Hypertension remains the most important modifiable risk factor for the development of cardiovascular disease. While it is clear that inflammation plays a pivotal role in the development and maintenance of hypertension, several novel discoveries have been made within the past decade that have advanced the field and have provided new mechanistic insights. First, recent studies have identified a central role of sodium-induced immune cell activation in the pathogenesis of hypertension by altering the gut microbiome and formation of products of lipid oxidation known as isolevuglandins. Second, cytokine elaboration by the inflammasome leading to end-organ dysfunction and immune activation has been found to play a role in the genesis of hypertension. Third, novel techniques have identified previously uncharacterized immune cell populations that may play a functional role in these processes. Finally, the role of inflammation in hypertension may be an important mediator of severe COVID-19 infections. In this review, we discuss these recent advances in the study of inflammation and hypertension and highlight topics for future studies.

Hypertension, a Moving Target in COVID-19

“…Inflammation is a complex process involving multiple cell types and secreted factors, many of which have been linked to hypertension. 59 – 61 The importance of the immune system in the pathophysiology of hypertension may relate primarily to its effects on inflammation, which is involved not only in BP regulation and thus in the development of hypertension, but also in the initiation and progression of cardiovascular and renal tissue damage/remodeling. 60 , 62 There is now extensive experimental and also clinical evidence that hypertension is associated with inflammation and immune cell activation, processes that are driven in large part by oxidative stress.…”

“… 60 , 62 , 64 The resulting molecular events induce protein oxidation and dysregulated cell signaling, leading to inflammation, cell migration, and immune cell activation, among many other effects. 59 – 61 …”

“…Although it has not yet been proven whether inflammation in humans is causatively related to hypertension or represents a secondary effect of hypertension, it is nevertheless clear that inflammation and the dysregulated immune system are closely linked, and that immunoinflammation plays an important role in hypertension. 60 , 61 Several factors involved in hypertension including genetic susceptibility, 65 neurohumoral activation, 64 , 66 salt (sodium), 67 – 69 and gut microbiome 68 , 70 among others may promote immunoinflammation in hypertension. Notwithstanding the complexity of the interplay of these factors, it has been suggested that oxidative stress and increased generation of reactive oxygen species represent a common molecular basis linking immunoinflammation in hypertension.…”

“… 60 , 62 Within the innate immune system, the NLRP3-related inflammasome in monocytes and dendritic cells may be particularly relevant in hypertension. 61 , 71 The mechanisms of immune cell activation and their effector functions in hypertension, including the complex interplay of different cell types and mediators, are still poorly defined. Nevertheless, the activation of several cytokines has been linked to hypertension in experimental and clinical studies.…”

Direct Detection of Isolevuglandins in Tissues using a D11 scFv-Alkaline Phosphatase Fusion Protein and Immunofluorescence

“…It is estimated that 92.1 million US adults have at least one of the US population 6 . Previous studies have found that inflammation is an underlying cause of hypertension and that IsoLGs play a role 7 . Hypertensive stimuli, including angiotensin II, catecholamines, aldosterone, and excess dietary salt, induce IsoLG accumulation in antigen presenting cells including dendritic cells (DCs), which in turn activate T cells to proliferate and produce inflammatory cytokines that contribute to hypertension 8 , 9 .…”