Cardiovascular extracellular microRNAs: emerging diagnostic markers and mechanisms of cell-to-cell RNA communication

Abstract

Cardiovascular diseases are a leading cause of morbidity and mortality in Western societies. It is now well established that microRNAs (miRNAs) are determinant regulators in various medical conditions including cardiovascular diseases. The recent discovery that miRNAs, while associated with different carriers, can be exported out of the cell, has triggered a renewed interest to analyze the potential to use extracellular miRNAs as tools for diagnostic and therapeutic studies. Circulating miRNAs in biological fluids present a technological advantage compared to current diagnostic tools by virtue of their remarkable stability and relative ease of detection rendering them ideal tools for non-invasive and rapid diagnosis. Extracellular miRNAs also represent a novel form of inter-cellular communication by transferring genetic information from a donor cell to a recipient cell. This review briefly summarizes recent insights in the origin, function and diagnostic potential of extracellular miRNAs by focusing on a select number of cardiovascular diseases.

MicroRNA-210 Enhances Fibrous Cap Stability in Advanced Atherosclerotic Lesions

“…1 Identification and stabilization of a vulnerable plaque would be of great value in patients at risk of lesion rupture. 13 We used a human array of lesion site plasma, obtained during CEA and laser capture microdissection (LCM) of plaque tissue, to identify miR-210 repression in high-grade carotid stenosis patients with symptoms of atherosclerotic plaque rupture versus asymptomatic CEA subjects. Using 2 distinct murine plaque models, we were able to decipher an antiapoptotic role for miR-210 in smooth muscle cell (SMC)-enriched fibrous caps, altering the pathological consequence in vivo.…”

Extracellular Micro-RNAs in Health and Disease: Basic Science, Biogenesis and Release

“…Recently, miR-423-5p, miR-18b-3p, miR-129-5p, miR-1254, miR-675, and miR-622) were reported to be elevated in patients with heart failure, with miR-423-5p positively correlated with N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and most strongly related to the clinical diagnosis of heart failure [75]. Besides, plasma levels of miR-208b and miR-499 both have been highly associated with AMI.…”

O presente e o futuro dos marcadores circulantes de câncer

“…Estudos recentes revelaram que as EV constituem-se numa forma normal de comunicação intercelular, inclusive a distância, desempenhando um papel importante. 7,9 A carga das EV é variável, podendo conter pedaços de DNA genômico, micro-RNA, RNA não codificante (ncRNA, non-coding), e mais raramente RNA m íntegro, RNAs do sistema de tradução (transportador e ribossomais), DNA mitocondrial, lipídeos etc. 7,9,10,11 A nomenclatura das EV também pode apresentar variações, sobretudo em trabalhos mais antigos.…”

“…Essas EV são secretadas por praticamente todas as células e são consideradas como mensageiros intercelulares. 7,9 O protocolo mais comum de isolamento dos exossomos envolve centrifugações sequenciais que começam com a velocidade de 300 xg, passando por 10.000 xg, 16.000 xg até chegar em 100.000 xg. Ou seja, velocidades muito altas somente alcançadas por ultracentrífugas.…”

“…20 O DNA tumoral circulante (ctDNA) -do inglês circulating tumor DNA -pode ser encontrado circulando livremente, tal como as proteínas. 7 Usando PCR digital, ctDNA de origem tumoral foi detectado em mais de 75% dos pacientes com câncer avançado de pâncreas, ovários, colorretal, bexiga, gastroesofaríngeo, mama, melanoma, hepatocelular e de cabeça e pescoço.…”