Adaptive immune disorders in hypertension and heart failure: focusing on T-cell subset activation and clinical implications

Abstract

Hypertension is a growing health concern worldwide. Established hypertension is a causative factor of heart failure, which is characterized by increased vascular resistance and intractable uncontrolled blood pressure. Hypertension and heart failure have multiple causes and complex pathophysiology but cellular immunity is thought to contribute to the development of both. Recent studies showed that T cells play critical roles in hypertension and heart failure in humans and animals, with various stimuli leading to the formation of effector T cells that infiltrate the cardiovascular wall. Monocytes/macrophages also accumulate in the cardiovascular wall. Various cytokines (e.g. interleukin-6, interleukin-17, interleukin-10, tumor necrosis factor-α, and interferon-γ) released from immune cells of various subtypes promote vascular senescence and elastic laminal degradation as well as cardiac fibrosis and/or hypertrophy, leading to cardiovascular structural alterations and dysfunction. Recent laboratory evidence has defined a link between inflammation and the immune system in initiation and progression of hypertension and heart failure. Moreover, cross-talk among natural killer cells, adaptive immune cells (T cells and B cells), and innate immune cells (i.e. monocytes, macrophages, neutrophils, and dendritic cells) contributes to end-cardiovasculature damage and dysfunction in hypertension and heart failure. Clinical and experimental studies on the diagnostic potential of T-cell subsets revealed that blood regulatory T cells, CD4+ cells, CD8+ T cells, and the ratio of CD4+ to CD8+ T cells show promise as biomarkers of hypertension and heart failure. Therapeutic interventions to suppress activation of these cells may prove beneficial in reducing end-organ damage and preventing consequences of cardiovascular failure, including hypertension of heart failure.

Hypertension is a risk factor for adverse outcomes in patients with coronavirus disease 2019: a cohort study

“…Some other hypotheses also seem to support the observed harmful effect of hypertension. Adaptive immune disorders might be one reason why people with hypertension are at a higher risk for coronavirus and disease progression [11]. While coronavirus also damages the heart directly [12], in patients with hypertension whose heart function has already been weakened by the effects of high blood pressure, the double-hit by the virus infection is likely to cause more severe injury.…”

Dieckol Reduces Muscle Atrophy by Modulating Angiotensin Type II Type 1 Receptor and NADPH Oxidase in Spontaneously Hypertensive Rats

“…Nox deletion in T cells demonstrated enhanced differentiation to nonpathogenic Th17 cells, secreting IL-10 [21,22]. Increasing inflammatory Th17 cells and decreasing Treg cells were known to be related to hypertension and sarcopenia [20,47].…”

Inhibition of Jumonji demethylases reprograms severe dilated cardiomyopathy and prolongs survival

“…EMT genes, and interferon gamma and alpha response gene sets behaved similarly. Given the roles of these pathways in promoting heart pathologies [44][45][46][47][48][49][50][51][52][53], their increased expression at late time points either renders JIB-04 ineffective at the given dose and/or indicates JIB-04 resistance has developed and expression goes back up. In contrast, fatty acid metabolism genes were enriched by JIB-04 at both early and later time points suggesting this transcriptional pathway is not a main contributor to changes seen in the survival benefit.…”