The role of extracellular vesicles in regulating local and systemic inflammation in cardiovascular disease

Abstract

Extracellular vesicles are heterogeneous structures surrounded by cell membranes and carry complex contents including nucleotides, proteins, and lipids. These proteins include cytokines and chemokines that are important for exaggerating local and systemic inflammation in disease. Extracellular vesicles are mainly categorized as exosomes and micro-vesicles, which are directly shed from the endosomal system or originated from the cell membrane, respectively. By transporting several bioactive molecules to recipient cells and tissues, extracellular vesicles have favorable, neutral, or detrimental impacts on their targets, such as switching cell phenotype, modulating gene expression, and controlling biological pathways such as inflammatory cell recruitment, activation of myeloid cells and cell proliferation. Extracellular vesicles mediate these functions via both autocrine and paracrine signaling. In the cardiovascular system, extracellular vesicles can be secreted by multiple cell types like cardiomyocytes, smooth muscle cells, macrophages, monocytes, fibroblasts, and endothelial cells, and affect functions of cells or tissues in distant organs. These effects involve maintaining homeostasis, regulating inflammation, and triggering pathological process in cardiovascular disease. In this review, we mainly focus on the role of micro-vesicles and exosomes, two important subtypes of extracellular vesicles, in local and systemic inflammation in cardiovascular diseases such as myocardial infarction, atherosclerosis and heart failure. We summarize recent findings and knowledge on the effect of extracellular vesicles in controlling both humoral and cellular immunity, and the therapeutic approaches to harness this knowledge to control exacerbated inflammation in cardiovascular diseases.