Inflammation, Immunity, and Hypertensive End-Organ Damage

Abstract

For more than 50 years, it has been recognized that immunity contributes to hypertension. Recent data have defined an important role of T cells and various T cell-derived cytokines in several models of experimental hypertension. These studies have shown that stimuli like angiotensin II, DOCA-salt and excessive catecholamines lead to formation of effector like T cells that infiltrate the kidney and perivascular regions of both large arteries and arterioles. There is also accumulation of monocyte/macrophages in these regions. Cytokines released from these cells, including IL-17, IFN-γ, TNFα and IL-6 promote both renal and vascular dysfunction and damage, leading to enhanced sodium retention and increased systemic vascular resistance. The renal effects of these cytokines remain to be fully defined, but include enhanced formation of angiotensinogen, increased sodium reabsorption and increased renal fibrosis. Very recent experiments have defined a link between oxidative stress and immune activation in hypertension. These have shown that hypertension is associated with formation of reactive oxygen species in dendritic cells that lead to formation of gamma ketoaldehydes, or isoketals. These rapidly adduct to protein lysines and are presented by dendritic cells as neoantigens that activate T cells and promote hypertension. Thus, cells of both the innate and adaptive immune system contribute to end-organ damage and dysfunction in hypertension. Therapeutic interventions to reduce activation of these cells may prove beneficial in reducing end-organ damage and preventing consequences of hypertension including myocardial infarction, heart failure, renal failure and stroke.

Immune Mechanisms in Arterial Hypertension

“…Currently, no drugs are available to accomplish this latter goal. 10 In addition, vaccines could be a therapeutic option for prevention or treatment of arterial hypertension.…”

“…[4][5][6] This seminal work has caused great interest in the immunologic aspects of hypertensive disease. [7][8][9][10] This review will give a brief overview of the components of the innate and adaptive arm of the immune system in hypertension and summarize recent advances in immunologic research, with a special focus on their potential relevance for hypertension and hypertensive endorgan damage. Very recent findings on the role of dendritic cells as well as CD8…”

Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension

“…Increasing evidence indicates that adaptive immunity and innate immunity play a key role in the pathogenesis of hypertension and in the associated end-organ damage (60). Pioneering studies in lymphocyte-deficient mice (Rag1 -/-mice) established that T lymphocytes are required for the BP elevations in several hypertension models (61).…”

Arterial hypertension, obesity and non-alcoholic fatty liver disease: is there any connection?

“…Consequently, the metabolic disorder in the liver is the background for the development of chronic inflammatory process of low severity [33]. It is shown that it is non-specific systemic inflammation that brings together into a unitary syndrome hypertension, increased body weight (especially abdominal obesity), dyslipidaemia and atherogenesis [81]. Significant (p < 0.001) increase in inflammation markers (TNF-a, IL-1, IL-6) and increase (p < 0.001) in the circulating immune complexes' level were identified in patients with comorbidity (a combination of hypertension, obesity and NAFLD [75].…”