Targeting a cell-specific microRNA repressor of CXCR4 ameliorates atherosclerosis in mice.

The CXC chemokine receptor 4 (CXCR4) in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) is crucial for vascular integrity. The atheroprotective functions of CXCR4 in vascular cells may be counteracted by atherogenic functions in other nonvascular cell types. Thus, strategies for cell-specifically augmenting CXCR4 function in vascular cells are crucial if this receptor is to be useful as a therapeutic target in treating atherosclerosis and other vascular disorders.

Orphan GPR26 Counteracts Early Phases of Hyperglycemia-Mediated Monocyte Activation and Is Suppressed in Diabetic Patients.

Diabetes is the ninth leading cause of death, with an estimated 1.5 million deaths worldwide. Type 2 diabetes (T2D) results from the body's ineffective use of insulin and is largely the result of excess body weight and physical inactivity.

A Non-Canonical Link between Non-Coding RNAs and Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are among the top leading causes of mortality worldwide. Besides canonical environmental and genetic changes reported so far for CVDs, non-coding RNAs (ncRNAs) have emerged as key regulators of genetic and epigenetic mechanisms involved in CVD progression. High-throughput and sequencing data revealed that almost 80% of the total genome not only encodes for canonical ncRNAs, such as micro and long ncRNAs (miRNAs and lncRNAs), but also generates novel non-canonical sub-classes of ncRNAs, such as isomiRs and miRNA- and lncRNA-like RNAs.

SARS-CoV-2, Cardiovascular Diseases, and Noncoding RNAs: A Connected Triad.

Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is characterized by important respiratory impairments frequently associated with severe cardiovascular damages. Moreover, patients with pre-existing comorbidity for cardiovascular diseases (CVD) often present a dramatic increase in inflammatory cytokines release, which increases the severity and adverse outcomes of the infection and, finally, mortality risk. Despite this evident association at the clinical level, the mechanisms linking CVD and COVID-19 are still blurry and unresolved.

MicroRNAs and Long Non-Coding RNAs as Potential Candidates to Target Specific Motifs of SARS-CoV-2.

The respiratory system is one of the most affected targets of SARS-CoV-2. Various therapies have been utilized to counter viral-induced inflammatory complications, with diverse success rates. Pending the distribution of an effective vaccine to the whole population and the achievement of "herd immunity", the discovery of novel specific therapies is to be considered a very important objective.

Plasma microRNA signature associated with retinopathy in patients with type 2 diabetes.

Diabetic retinopathy (DR) is a leading cause of vision loss and disability. Effective management of DR depends on prompt treatment and would benefit from biomarkers for screening and pre-symptomatic detection of retinopathy in diabetic patients. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression which are released in the bloodstream and may serve as biomarkers.

Autophagy unleashes noncanonical microRNA functions.

MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression which act by guiding AGO (argonaute) proteins to target RNA transcripts in the RNA-induced silencing complex (RISC). This macromolecular complex includes multiple additional components (., TNRC6A) that allow for interaction with enzymes mediating inhibition of translation or RNA decay.

Noncanonical inhibition of caspase-3 by a nuclear microRNA confers endothelial protection by autophagy in atherosclerosis.

MicroRNAs (miRNAs) are versatile regulators of gene expression with profound implications for human disease including atherosclerosis, but whether they can exert posttranslational functions to control cell adaptation and whether such noncanonical features harbor pathophysiological relevance is unknown. Here, we show that miR-126-5p sustains endothelial integrity in the context of high shear stress and autophagy. Bound to argonaute-2 (Ago2), miR-126-5p forms a complex with Mex3a, which occurs on the surface of autophagic vesicles and guides its transport into the nucleus.

MicroRNA signatures in cardiac biopsies and detection of allograft rejection.

Background: Identification of heart transplant (HTx) rejection currently relies on immunohistology and immunohistochemistry. We aimed to identify specific sets of microRNAs (miRNAs) to characterize acute cellular rejection (ACR), antibody-mediated rejection (pAMR), and mixed rejection (MR) in monitoring formalin-fixed paraffin-embedded (FFPE) endomyocardial biopsies (EMBs) in HTx patients.

Methods: In this study we selected 33 adult HTx patients.

miR-103 promotes endothelial maladaptation by targeting lncWDR59.

Blood flow at arterial bifurcations and curvatures is naturally disturbed. Endothelial cells (ECs) fail to adapt to disturbed flow, which transcriptionally direct ECs toward a maladapted phenotype, characterized by chronic regeneration of injured ECs. MicroRNAs (miRNAs) can regulate EC maladaptation through targeting of protein-coding RNAs.

Dicer in Macrophages Prevents Atherosclerosis by Promoting Mitochondrial Oxidative Metabolism.

Background: Alternative macrophage activation, which relies on mitochondrial oxidative metabolism, plays a central role in the resolution of inflammation and prevents atherosclerosis. Moreover, macrophages handle large amounts of cholesterol and triglycerides derived from the engulfed modified lipoproteins during atherosclerosis. Although several microRNAs regulate macrophage polarization, the role of the microRNA-generating enzyme Dicer in macrophage activation during atherosclerosis is unknown.

Low nanomolar caffeic acid attenuates high glucose-induced endothelial dysfunction in primary human umbilical-vein endothelial cells by affecting NF-κB and Nrf2 pathways.

Hyperglycemia contributes to dysregulate endothelial function associated with diabetes, leading to initiation and propagation of vascular complications and dysfunction. Caffeic acid (CA), a dietary hydroxycinnamic acid abundant in coffee, has been reported to exert antidiabetic effects in rat models. Herein, we investigated the molecular effects of physiological concentrations of CA (10 nM) against endothelial dysfunction induced by high glucose (HG) in human endothelial cells (HUVECs).

Endothelial Dicer promotes atherosclerosis and vascular inflammation by miRNA-103-mediated suppression of KLF4.

MicroRNAs regulate the maladaptation of endothelial cells (ECs) to naturally occurring disturbed blood flow at arterial bifurcations resulting in arterial inflammation and atherosclerosis in response to hyperlipidemic stress. Here, we show that reduced endothelial expression of the RNAse Dicer, which generates almost all mature miRNAs, decreases monocyte adhesion, endothelial C-X-C motif chemokine 1 (CXCL1) expression, atherosclerosis and the lesional macrophage content in apolipoprotein E knockout mice (Apoe(-/-)) after exposure to a high-fat diet. Endothelial Dicer deficiency reduces the expression of unstable miRNAs, such as miR-103, and promotes Krüppel-like factor 4 (KLF4)-dependent gene expression in murine atherosclerotic arteries.

Nanomolar Caffeic Acid Decreases Glucose Uptake and the Effects of High Glucose in Endothelial Cells.

Epidemiological studies suggest that moderate and prolonged consumption of coffee is associated with a reduced risk of developing type 2 diabetes but the molecular mechanisms underlying this effect are not known. In this study, we report the effects of physiological concentrations of caffeic acid, easily achievable by normal dietary habits, in endothelial cells cultured in 25 mM of glucose (high glucose, HG). In HG, the presence of 10 nM caffeic acid was associated with a decrease of glucose uptake but not to changes of GLUT-1 membrane localization or mRNA levels.

Vitamin C supplementation modulates gene expression in peripheral blood mononuclear cells specifically upon an inflammatory stimulus: a pilot study in healthy subjects.

In order to study the effects of vitamin C supplementation on gene expression and compare its action between physiological and inflammatory conditions, a pilot study was set up utilizing microarray and qPCR technologies. Five healthy volunteers were supplemented with 1 g vitamin C (Redoxon(®)) per day for five consecutive days. Peripheral blood mononuclear cells (PBMNC) were isolated before and just after the last supplementation, and RNA was isolated for the Affymetrix gene 1.

Absorption, metabolism, and effects at transcriptome level of a standardized French oak wood extract, Robuvit, in healthy volunteers: pilot study.

The consumption of wine and spirits, traditionally aged in oak barrels, exposes humans to roburin ingestion. These molecules belong to a class of ellagitannins (ETs), and their only known source is oak wood. Very little is currently known about roburin bioavailability and biological activity.