Mechanisms in hypertension and target organ damage: Is the role of the thymus key? (Review)

Abstract

A variety of cells and cytokines have been shown to be involved in the whole process of hypertension. Data from experimental and clinical studies on hypertension have confirmed the key roles of immune cells and inflammation in the process. Dysfunction of the thymus, which modulates the development and maturation of lymphocytes, has been shown to be associated with the severity of hypertension. Furthermore, gradual atrophy, functional decline or loss of the thymus has been revealed to be associated with aging. The restoration or enhancement of thymus function via upregulation in the expression of thymus transcription factors forkhead box N1 or thymus transplantation may provide an option to halt or reverse the pathological process of hypertension. Therefore, the thymus may be key in hypertension and associated target organ damage, and may provide a novel treatment strategy for the clinical management of patients with hypertension in addition to different commercial drugs. The purpose of this review is to summarize and discuss the advances in our understanding of the impact of thymus function on hypertension from data from animal and human studies, and the potential mechanisms.

Figure 1

Factors involved in hypertension. Various types of cells and cytokines and the autonomic nervous system are affected by thymus function, and may be involved in the process of hypertension and target organ damage. Ang II, angiotensin II; ROS, reactive oxygen species; NK, natural killer T cell; DC, dendritic cell; APC, antigen-presenting cell; Th, T helper; Treg, regulatory T cell; Tc, cytotoxic T cell; IL, interleukin; IFN, interferon; CNS, central nervous system; Ras, renin-angiotensin system.

Figure 2

Role of the thymus in hypertension and target organ damage. Thymus dysfunction leads to the imbalance of T cell subsets and a change in the secretion of Tβ4, thereby aggravating the progression of hypertension and target organ damage, in addition to other cardiovascular events. Tβ4, thymosin β4; Ang II, angiotensin II; ATRAP, Ang II type 1 receptor-associated protein; Foxn1, forkhead box N1; POP, prolyl oligopeptidase; Ac-SDKP, N-acetyl-seryl-aspartyl-lysyl-proline; Th, T helper; Tc, cytotoxic T cell; Tregs, regulatory T cells.