Immune System and Microvascular Remodeling in Humans

Abstract

Low-grade inflammatory processes and related oxidative stress may have a key role in the pathogenesis of hypertension and hypertension-mediated organ damage. Innate immune cells, such as neutrophils, dendritic cells, monocytes/macrophages, as well as unconventional T lymphocytes like γδ T cells contribute to hypertension and may trigger vascular inflammation. Adaptive immunity has been demonstrated to participate in elevation of blood pressure and in vascular and kidney injury. In particular, effector T lymphocytes (Th1, Th2, and Th17) may play a relevant role in promoting hypertension and microvascular remodeling, whereas T-regulatory lymphocytes may have a protective role. Effector cytokines produced by these immune cells lead to increased oxidative stress, endothelial dysfunction and contribute to target organ damage in hypertension. A possible role of immune cell subpopulations in the development and regression of microvascular remodeling has also been proposed in humans with hypertension. The present review summarizes the key immune mechanisms that may participate in the pathophysiology of hypertension-mediated inflammation and vascular remodeling; advances in this field may provide the basis for novel therapeutics for hypertension.

Growing Heart Failure Burden of Hypertensive Heart Disease: A Call to Action

“…The contribution of HHD to the pathophysiology of HF in hypertension is the result of a sequential and complex process (reviewed in Messerli et al Accumulating data highlight the contributing role of nonhemodynamic mechanisms in the pathophysiology of HHD. Specifically, interconnected mechanisms related to alterations of immunity, oxidation/antioxidation balance, and endothelial function may be potential contributors to cardiac (and other target-organ) damage in hypertension (reviewed in Rizzoni et al 15 and Griendling et al 16 ). Additionally, it is important to consider that the timing and manifestations of the process leading to HHD and its clinical evolution may be individually modulated by several factors including demographics.…”

Genetic Modifications to Alter Blood Pressure Level

“…A growing body of evidence has emerged in the last decade suggesting the pathogenic aspects of innate and adaptive immune responses on the development and progression of hypertension and hypertensive end-organ damages. The possible mechanisms have been well reviewed [ 57 , 58 , 59 ]; herein, we shortly highlight recent findings on this topic ( Table 3 ). Among various subpopulations of immune cells, previous reports indicate that T cells especially have diverse contributions to the etiology [ 56 ].…”

The Role of N6-Methyladenosine Modification in Microvascular Dysfunction

“…Microvascular remodeling is defined as structural or functional adaptations of the microvasculature. Either neovascularization or microvascular malformation can progress into microvascular remodeling ( Figure 1 ) [ 62 ]. Herein, we have summarized associations between aberrantly changed expression of m 6 A regulators and microvascular remodeling in Table 3.…”

“…Inflammation-related microvascular remodeling is driven by migration of inflammatory cells, which is mediated by adhesion molecules, such as intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin [ 62 ]. In atherosclerosis, METTL3 promoted microvascular remodeling by upregulating the expression of NLR family pyrin domain containing 1 (NRLP1), a gene generating inflammasomes, with YTHDF1 as the reader [ 68 ].…”