Disparate miRNA expression in serum and plasma of patients with acute myocardial infarction: a systematic and paired comparative analysis

Despite the promising value of miRNAs in the diagnostic and prognostic of cardiovascular disease (CVD), recent meta-analyses did not support their potential. Methodological variances in studies may interfere with miRNA profle and afect their results. This study determines if the blood starting material is a source of variance in miRNA profle by performing a paired comparison in plasma and serum of the expression of primary miRNAs associated with CVD. Circulating miRNA yield was similar in both plasma and serum, although a signifcant increase was observed in patients with Non-ST-elevation myocardial infarction (NSTEMI) compared to control volunteers. When normalized by the expression of miR-484, diferent patterns of miRNA expression between serum and plasma. Although NSTEMI modifed the expression of miR-1 and miR-208 in both serum and plasma, plasma displayed a higher variance than serum (Levene's test p<0.01). For miR-133a and miR-26a, diferences were only detected in serum (p=0.0240), and conversely, miR-499a showed diferences only in plasma of NSTEMI (p=0.001). Interestingly, miR-21 showed an opposite pattern of expression, being increased in serum (2−ΔΔCt : 5.7, p=0.0221) and decreased in plasma (2−ΔΔCt : 0.5, p=0.0107). Plasma and serum exhibit diferent patterns of circulating miRNA expression in NSTEMI and suggest that results from studies with diferent starting material could not be comparable

Disparate miRNA expression in serum and plasma of patients with acute myocardial infarction: a systematic and paired comparative analysis

Despite the promising value of miRNAs in the diagnostic and prognostic of cardiovascular disease (CVD), recent meta-analyses did not support their potential. Methodological variances in studies may interfere with miRNA profle and afect their results. This study determines if the blood starting material is a source of variance in miRNA profle by performing a paired comparison in plasma and serum of the expression of primary miRNAs associated with CVD. Circulating miRNA yield was similar in both plasma and serum, although a signifcant increase was observed in patients with Non-ST-elevation myocardial infarction (NSTEMI) compared to control volunteers. When normalized by the expression of miR-484, diferent patterns of miRNA expression between serum and plasma. Although NSTEMI modifed the expression of miR-1 and miR-208 in both serum and plasma, plasma displayed a higher variance than serum (Levene's test p<0.01). For miR-133a and miR-26a, diferences were only detected in serum (p=0.0240), and conversely, miR-499a showed diferences only in plasma of NSTEMI (p=0.001). Interestingly, miR-21 showed an opposite pattern of expression, being increased in serum (2−ΔΔCt:5.7, p=0.0221) and decreased in plasma (2−ΔΔCt: 0.5, p=0.0107). Plasma and serum exhibit diferent patterns of circulating miRNA expression in NSTEMI and suggest that results from studies with diferent starting material could not be comparable

Expression associates with inflammation in early atherosclerosis in humans and can be therapeutically silenced to reduce NF-κB activation and atherogenesis in mice

Background:\ua0Chronic activation of the innate immune system drives inflammation and contributes directly to atherosclerosis. Previously, we showed that macrophages in the atherogenic plaque undergo RIPK3-MLKL-dependent programmed necroptosis in response to sterile ligands such as oxidized LDL and damage-associated patterns (DAMPs) and necroptosis is active in advanced atherosclerotic plaques. Upstream of the RIPK3-MLKL necroptotic machinery lies RIPK1, which acts as a master switch that controls whether the cell undergoes NFκB-dependent inflammation, caspase-dependent apoptosis or necroptosis in response to extracellular stimuli. We therefore set out to investigate the role of RIPK1 in the development of atherosclerosis, which is largely driven by NFκB-dependent inflammation at early stages. We hypothesize that, unlike RIPK3 and MLKL, RIPK1 primarily drives NFκB-dependent inflammation in early atherogenic lesions and knocking down RIPK1 will reduce inflammatory cell activation and protect against the progression of atherosclerosis.Methods:\ua0We examined expression of RIPK1 protein and mRNA in both human and mouse atherosclerotic lesions, and using loss-of-function approaches in vitro in macrophages and endothelial cells to measure inflammatory responses. We administered weekly injections of RIPK1 anti-sense oligonucleotides (ASO) to\ua0Apoe-/-\ua0mice fed a cholesterol-rich (Western) diet for 8 weeks.Results:\ua0We find RIPK1 expression is abundant in early-stage atherosclerotic lesions in both humans and mice. Treatment with RIPK1 ASOs led to a reduction in aortic sinus and\ua0en face\ua0lesion areas (47.2% or 58.8% decrease relative to control,