Abstract

Significance: Abdominal aortic aneurysm (AAA) is a potentially fatal condition, featuring the possibility of high-mortality rupture. To date, prophylactic surgery by means of open surgical repair or endovascular aortic repair at specific thresholds is considered standard therapy. Both surgical options hold different risk profiles of short- and long-term morbidity and mortality. Targeting early stages of AAA development to decelerate disease progression is desirable.Recent Advances: Understanding the pathomechanisms that initiate formation, maintain growth, and promote rupture of AAA is crucial to developing new medical therapeutic options. Inflammatory cells, in particular macrophages, have been investigated for their contribution to AAA disease for decades, whereas evidence on lymphocytes, mast cells, and neutrophils is sparse. Recently, there has been increasing interest in noncoding RNAs (ncRNAs) and their involvement in disease development, including AAA.Critical Issues: The current evidence on myeloid cells and ncRNAs in AAA largely originates from small animal models, making clinical extrapolation difficult. Although it is feasible to collect surgical human AAA samples, these tissues reflect end-stage disease, preventing examination of critical mechanisms behind early AAA formation.Future Directions: Gaining more insight into how myeloid cells and ncRNAs contribute to AAA disease, particularly in early stages, might suggest nonsurgical AAA treatment options. The utilization of large animal models might be helpful in this context to help bridge translational results to humans.

Highlights

  • The prevalence of unhealthy diets, smoking, and inactive lifestyles in conjunction with an aging society has laid the cornerstones for cardiovascular diseases being a major public health burden in the developed world

  • This review aims to give an overview on the role of myeloid cells and noncoding RNAs as potential targets for future therapeutic approaches to cure Abdominal aortic aneurysm (AAA) disease

  • Myeloid cells are involved in AAA development and growth

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Summary

Introduction

The prevalence of unhealthy diets, smoking, and inactive lifestyles in conjunction with an aging society has laid the cornerstones for cardiovascular diseases being a major public health burden in the developed world. Monocyte-derived macrophages in AAA patients differ from those in PAOD patients in terms of protein and gene expression, suggesting specific involvement in AAA disease. Those derived from AAA patients showed differences in expression of proteins related to extracellular matrix (ECM; e.g., beta-actin and fibronectin) and inflammation (e.g., tissue inhibitor of metalloproteinases [TIMP]-3) [61]. Similar results showed elevated monocyte levels [lymphocyte antigen (LY)6Chigh and lymphocyte antigen LY6Clow monocytes] after AngII infusion in mice that later developed AAA These monocyte subsets were shown to have been mobilized from the spleen rather than the bone marrow. Conversion of monocyte subsets from the classical toward nonclassical subsets over the time course of disease was demonstrated for other conditions (e.g., myocardial infarction and rheumatoid arthritis) [59]

Conclusions and Future Directions
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