Profile of serum microRNAs in heart failure with reduced and preserved ejection fraction: Correlation with myocardial remodeling.

Background and aims: Cardiomyocyte hypertrophy and interstitial fibrosis are key components of myocardial remodeling in Heart Failure (HF) with preserved (HFpEF) or reduced ejection fraction (HFrEF). MicroRNAs (miRNAs) are non-coding, evolutionarily conserved RNA molecules that may offer novel insights into myocardial remodeling. This study aimed to characterize miRNA expression in HFpEF (LVEF ≥ 45%) and HFrEF (LVEF < 45%) and its association with myocardial remodeling. Methods: Prospectively enrolled symptomatic HF patients (HFpEF:n = 36; HFrEF:n = 31) and controls (n = 23) underwent cardiac magnetic resonance imaging with T1-mapping and circulating miRNA expression (OpenArray system). Results: 13 of 188 miRNAs were differentially expressed between HF groups (11 downregulated in HFpEF). Myocardial extracellular volume (ECV) was increased in both HF groups (HFpEF 30 ± 5%; HFrEF 30 ± 3%; controls 26 ± 2%, p < 0.001). miR-128a-3p, linked to cardiac hypertrophy, fibrosis, and dysfunction, correlated positively with ECV in HFpEF (r = 0.60, p = 0.01) and negatively in HFrEF (r = -0.51, p = 0.04). miR-423-5p overexpression, previously associated HF mortality, was inversely associated with LVEF (r = - 0.29, p = 0.04) and intracellular water lifetime (τic) (r = -0.45, p < 0.05) in both HF groups, and with NT-proBNP in HFpEF (r = -0.63, p < 0.01). Conclusions: miRNA expression profiles differed between HF phenotypes. The differential expression and association of miR-128a-3p with ECV may reflect the distinct vascular, interstitial, and cellular etiologies of HF phenotypes.

Relationship Between Circulating MicroRNAs and Left Ventricular Hypertrophy in Hypertensive Patients.

Objective: Left ventricular hypertrophy (LVH) is a common complication of hypertension and microRNAs (miRNAs) are considered to play an important role in cardiac hypertrophy development. This study evaluated the relationship between circulating miRNAs and LVH in hypertensive patients. Methods: Two cohorts [exploratory (n = 42) and validation (n = 297)] of hypertensive patients were evaluated by clinical, laboratory and echocardiography analysis. The serum expression of 754 miRNAs in the exploratory cohort and 6 miRNAs in the validation cohort was evaluated by the TaqMan OpenArray® system and quantitative polymerase chain reaction, respectively. Results: Among the 754 analyzed miRNAs, ten miRNAs (miR-30a-5p, miR-let7c, miR-92a, miR-451, miR-145-5p, miR-185, miR-338, miR-296, miR-375, and miR-10) had differential expression between individuals with and without LVH in the exploratory cohort. Results of multivariable regression analysis adjusted for confounding variables showed that three miRNAs (miR-145-5p, miR-451, and miR-let7c) were independently associated with LVH and left ventricular mass index in the validation cohort. Functional enrichment analysis demonstrated that these three miRNAs can regulate various genes and pathways related to cardiac remodeling. Furthermore, in vitro experiments using cardiac myocytes demonstrated that miR-145-5p mimic transfection up-regulated the expression of brain and atrial natriuretic peptide genes, which are markers of cardiac hypertrophy, while anti-miR-145-5p transfection abrogated the expression of these genes in response to norepinephrine stimulus. Conclusions: Our data demonstrated that circulating levels of several miRNAs, in particular miR-145-5p, miR-451, and let7c, were associated with LVH in hypertensive patients, indicating that these miRNAS may be potential circulating biomarkers or involved in hypertension-induced LV remodeling.

Association of Circulating miR-145-5p and miR-let7c and Atherosclerotic Plaques in Hypertensive Patients.

AIM: Hypertension is a strong risk factor for atherosclerosis. Increased carotid intima-media thickness (cIMT) and carotid plaques are considered subclinical markers of atherosclerosis. This study aimed at evaluating the serum expression of miRNAs previously related to adverse vascular remodeling and correlating them with carotid plaques and cIMT in hypertensive patients. METHODS: We cross-sectionally evaluated the clinical and carotid characteristics as well as serum expression of miR-145-5p, miR-let7c, miR-92a, miR-30a and miR-451 in 177 hypertensive patients. Carotid plaques and cIMT were evaluated by ultrasound, and the expression of selected miRNAs was evaluated by a quantitative polymerase chain reaction. RESULTS: Among all participants (age = 60.6 ± 10.7 years, 43% males), there were 59% with carotid plaques. We observed an increased expression of miR-145-5p (Fold Change = 2.0, p = 0.035) and miR-let7c (Fold Change = 3.8, p = 0.045) in participants with atherosclerotic plaque when compared to those without plaque. In the logistic regression analysis adjusted for relevant covariates, these miRNAs showed a stronger association with carotid plaques (miR-145-5p: Beta ± SE = 0.050 ± 0.020, p = 0.016 and miR-let7c: Beta ± SE = 0.056 ± 0.019, p = 0.003). CONCLUSIONS: Hypertensive patients with carotid plaques have an increased expression of miR-145-5p and miR-let7c, suggesting a potential role of these miRNAs as a biomarker for subclinical atherosclerosis in hypertensive individuals.

Bioinformatics analysis of circulating miRNAs related to cancer following spinal cord injury.

Patients with spinal cord injury (SCI) have an increased risk of developing esophageal, bladder and hematologic malignancies compared with the normal population. In the present study, we aimed to identify, through in silico analysis, miRNAs and their target genes related to the three most frequent types of cancer in individuals with SCI. In a previous study, we reported a pattern of expression of miRNAs in 17 sedentary SCI males compared with 22 healthy able-bodied males by TaqMan OpenArray. This list of miRNAs deregulated in SCI patients was uploaded to miRWALK2.0 to predict the target genes and pathways of selected miRNAs. We used Cytoscape software to construct the network displaying the miRNAs and their gene targets. Among the down-regulated miRNAs in SCI, 21, 19 and 20 miRNAs were potentially associated with hematological, bladder and esophageal cancer, respectively, and three target genes (TP53, CCND1 and KRAS) were common to all three types of cancer. The three up-regulated miRNAs were potentially targeted by 18, 15 and 10 genes associated with all three types of cancer. Our current bioinformatics analysis suggests the potential influence of several miRNAs on the development of cancer in SCI. In general, these data may provide novel information regarding potential molecular mechanisms involved in the development of cancer among individuals with SCI. Further studies aiming at understanding how miRNAs contribute to the development of the major cancers that affect patients after SCI may help elucidate the role of these molecules in the pathophysiology of the disease.