Circulating miR-200c is up-regulated in paediatric patients with familial hypercholesterolaemia and correlates with miR-33a/b levels: implication of a ZEB1-dependent mechanism

Abstract

Hypercholesterolaemia provokes reactive oxygen species (ROS) increase and is a major risk factor for cardiovascular disease (CVD) development. We previously showed that circulating expression levels were up-regulated in children with familial hypercholesterolaemia (FH). control cholesterol homoeostasis and recently has been demonstrated to directly target the transcription factor zinc finger E-box-binding homeobox 1 (ZEB1). The latter acts in a negative feedback loop with the family. Our previous studies showed that the ROS-dependent up-regulation induces endothelial dysfunction and provokes a ZEB1-dependent apoptosis and senescence. In the present study, we aimed to verify whether circulating was induced in FH children, and whether a correlation existed with Total RNA was extracted from plasma of 28 FH children and 25 age-matched healthy subjects (HS) and levels were measured. We found that was up-regulated in FH compared with HS (4.00 ± 0.48-fold increase, <0.05) and exhibited a positive correlation with did not correlate with plasma lipids, but correlated with C-reactive protein (CRP) plasma levels and glycaemia (GLI). Ordinary least squares (OLS) regression analysis revealed that was significantly affected by GLI and by (<0.01; <0.001 respectively). Moreover, we found that overexpression, in different cell lines, decreased ZEB1 expression and up-regulated both the intracellular and the extracellular expression levels. In conclusion, circulating is up-regulated in FH, probably due to oxidative stress and inflammation and via a-ZEB1-dependent mechanism. The present study could provide the first evidence to point to the use of and, as early biomarkers of CVD, in paediatric FH.

MicroRNAs targeting the SARS-CoV-2 entry receptor ACE2 in cardiomyocytes

“…The miR-200 family, comprising of miR-200b, miR-200c and miR-429, is a well-known miRNA cluster which is highly investigated in anti-cancer studies [15]. Also, it has been previously shown that miR-200c is upregulated in CVDs [16]. Here, we elucidated the role of miR-200c in SARS-CoV-2 infection where the overexpression of miR-200c represses ACE2 expression in both rat and human cardiomyocytes.…”

The Oxidative Stress-Induced miR-200c Is Upregulated in Psoriasis and Correlates with Disease Severity and Determinants of Cardiovascular Risk

“…The miR-200 family was shown to be induced by oxidative stress and to play an important role in endothelial function; in particular, miR-200c induces EC apoptosis, senescence, and dysfunction [24,25]. Moreover, circulating miR-200c is upregulated in FH in pediatric age, a disease characterized by oxidative stress increase and precocious atherosclerosis [26]. miR-200c increases also in carotid plaques, and its expression is higher in unstable vs. stable plaques and is upregulated in the plasma of atherosclerotic patients.…”

“…Thus, miR-200c upregulation causes ROS increase and NO production decrease [25]. Moreover, we have previously shown that circulating miR-200c is significantly upregulated in familial hypercholesterolemia (FH) patients in pediatric age [26], a disease associated with high oxidative stress levels and early atherosclerosis [27,28].…”

Molecular therapies delaying cardiovascular aging: disease- or health-oriented approaches

“…miRNA-200c also plays a major role in cardiovascular diseases (19). miRNA-200c is upregulated in plaques and plasma of atherosclerotic patients, being further enhanced in unstable vs stable carotid plaques (23) and in plasma of children with familiar hypercholesterolemia (24).…”

“…miRNA-200c also plays a major role in cardiovascular diseases ( 19 ). miRNA-200c is upregulated in plaques and plasma of atherosclerotic patients, being further enhanced in unstable vs stable carotid plaques ( 23 ) and in plasma of children with familiar hypercholesterolemia ( 24 ). miRNA-200c was found upregulated in cardiomyopathies induced by doxorubicin (DOX) in mice as well as in human cardiac mesenchymal progenitor cells exposed to DOX ( 25 ).…”