miR-146a in Cardiovascular Diseases and Sepsis: An Additional Burden in the Inflammatory Balance?

Abstract

The new concept of thrombosis associated with an inflammatory process is called thromboinflammation. Indeed, both thrombosis and inflammation interplay one with the other in a feed forward manner amplifying the whole process. This pathological reaction in response to a wide variety of sterile or non-sterile stimuli eventually causes acute organ damage. In this context, neutrophils, mainly involved in eliminating pathogens as an early barrier to infection, form neutrophil extracellular traps (NETs) that are antimicrobial structures responsible of deleterious side effects such as thrombotic complications. Although NETosis mechanisms are being unraveled, there are still many regulatory elements that have to be discovered. miRNAs are important modulators of gene expression implicated in human pathophysiology almost two decades ago. Among the different miRNAs implicated in inflammation, miR-146a is of special interest because: (i) it regulates among others, TLR/NF-B axis which is of paramount importance in inflammatory processes, (ii) it regulates the formation of NETs by modifying their ageing phenotype, (iii) it has expression levels that may decrease among individuals up to 50%, controlled in part by the presence of several polymorphisms. In this manuscript, we will review the main characteristics of miR-146a biology. In addition, we will detail how miR-146a is implicated in the development of two paradigmatic diseases in which thrombosis and inflammation interact, cardiovascular diseases and sepsis, and their association with the presence of miR-146a polymorphisms and the use of miR-146a as a marker of cardiovascular diseases and sepsis.

Epigenetic Effect of MicroRNA in Coronary Heart Disease With and Without Diabetes

“…Microribonucleic acids (miRNAs) are of particular interest in this field, including miR-146a. It has been widely studied because of its important regulatory role in inflammatory and immune processes 20,21 . Recently, the association between miRNAs polymorphisms in CHD and diabetes risks are drawing more attention 22,23 .…”

A Rollercoaster Plunge into 2022

“…In 2020, we introduced optional “Visual Summaries” to convey the main message of the manuscript in a clear and concise graphic manner so that readers can grasp its contents and relevance at a glance. In the past two years, we have received an increasing number of such graphical abstracts which greatly improved the reading quality of the articles published 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 some of which have even been selected for the T&H Issue Cover 4 5 11 15 33 38 ( Fig. 2 ).…”

The Regulatory Role of MicroRNAs on Phagocytes: A Potential Therapeutic Target for Chronic Diseases

“…In terms of pro-inflammatory, up-regulation of miR-146a, miR-887-3p, miR-155, and down-regulation of miR-223-3p play important roles. miR-146a modulates inflammatory responses by inhibiting the Toll-like receptor/NF-κB axis and sod2 and modulates NET formation by altering its senescence phenotype ( 136 , 137 ). MiR-887-3p released by neutrophils increases endothelial release of chemokines and promotes transendothelial leukocyte migration ( 138 ).…”