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.

Myocardial Oedema as a Consequence of Viral Infection and Persistence – a Narrative Review with Focus on COVID-19 and Post COVID Sequelae

“…Viral infections lead to systemic inflammatory processes affecting (micro-) vascular homeostasis [28][29][30]296]. During the acute phase, rapid cellular entry is facilitated through the destabilization of the protective endothelial shield, the glycocalyx [296].…”

“…The breakdown of the endothelial barrier leads to enhanced permeability shifting inflammatory processes to adjacent tissues [296]. The chronic phase comprises viral persistence and sub-clinical inflammation triggering immunothrombosis, oedema formation, tissue necrosis and, more specifically, myocardial remodelling resulting in heart failure [1,4,28,29,183,269,365,380].…”

“…Recent guidelines recommend sodium-glucose cotransporter 2 inhibitors (SGLT-2i) in heart failure patients to reduce the risk for hospitalisation and cardiovascular death [214,439,440]. Though SGLT-2i are suggested to have anti-inflammatory properties and counteract myocardial fibrosis, an improvement of patient survival during hospitalised COVID-19 infection could hitherto not be shown in a metaanalysis including the DARE-19, RECOVERY and ACTIV-4A trial [29,[441][442][443][444][445]. Another drug class recommended for heart failure treatment are mineralocorticoid receptor antagonists [214,440].…”

“…Furthermore, the interaction of pathological processes initiated or exacerbated by MO, including inflammation, endothelial cell dysfunction, release of reactive oxygen species and proinflammatory cytokine signalling, contribute to a vicious circle of immunothrombosis, ultimately leading to tissue necrosis, fibrosis and organ failure [28][29][30].…”

Myocardial Oedema as a Consequence of Viral Infection and Persistence—A Narrative Review with Focus on COVID-19 and Post COVID Sequelae

“…Numerous reports suggest a major role for inflammation and hypoxia in the development of microvascular obstruction and dysfunction; this triggers not only chronic atherosclerotic processes but can lead to acute myocardial injury including infarction with potentially lethal complications [ 104 , 107 , 108 , 109 , 110 ]. Herein, the high presence of fibrin-rich micro-thrombi in myocardial capillaries, arterioles, as well as small muscular arteries, drives myocardial injury and tissue necrosis [ 111 ].…”