Micro- and Macrovascular Effects of Inflammation in Peripheral Artery Disease-Pathophysiology and Translational Therapeutic Approaches

Abstract

Inflammation has a critical role in the development and progression of atherosclerosis. On the molecular level, inflammatory pathways negatively impact endothelial barrier properties and thus, tissue homeostasis. Conformational changes and destruction of the glycocalyx further promote pro-inflammatory pathways also contributing to pro-coagulability and a prothrombotic state. In addition, changes in the extracellular matrix composition lead to (peri-)vascular remodelling and alterations of the vessel wall, e.g., aneurysm formation. Moreover, progressive fibrosis leads to reduced tissue perfusion due to loss of functional capillaries. The present review aims at discussing the molecular and clinical effects of inflammatory processes on the micro- and macrovasculature with a focus on peripheral artery disease.

Keywords: atherosclerosis; endothelial dysfunction; glycocalyx; inflammation; peripheral artery disease.

Figure 1

Pathophysiologic consequences of inflammation on the vasculature and adjacent tissue: Inflammatory processes promotes endothelial dysfunction by glycocalyx degradation, leading to altered vascular homeostasis [9]. The pathological processes influence each other, perpetuating disease progression. ETosis, extracellular trap formation; I/R, ischaemia-reperfusion injury; MPs, microparticles; ROS, reactive oxygen species; TLR, toll-like receptor.