LncRNA DANCR promotes macrophage lipid accumulation through modulation of membrane cholesterol transporters.

The progression of atherosclerosis (AS), the pathological foundation of coronary artery disease (CAD), is featured by massive lipid deposition in the vessel wall. LncRNAs are implicated in lipid disorder and AS, whereas the specific role of lncRNA DANCR in atherogenesis remains unknown. Here, we demonstrated that DANCR promotes macrophage lipid accumulation by regulating the expression of membrane cholesterol transport proteins.

Opposing actions of CRF-R1 and CB1 receptor on facial stimulation-induced MLI-PC plasticity in mouse cerebellar cortex.

Background: Corticotropin-releasing factor (CRF) is the major neuromodulator orchestrating the stress response, and is secreted by neurons in various regions of the brain. Cerebellar CRF is released by afferents from inferior olivary neurons and other brainstem nuclei in response to stressful challenges, and contributes to modulation of synaptic plasticity and motor learning behavior via its receptors. We recently found that CRF modulates facial stimulation-evoked molecular layer interneuron-Purkinje cell (MLI-PC) synaptic transmission via CRF type 1 receptor (CRF-R1) in vivo in mice, suggesting that CRF modulates sensory stimulation-evoked MLI-PC synaptic plasticity.

Pharmacological inhibition of arachidonate 12-lipoxygenase ameliorates myocardial ischemia-reperfusion injury in multiple species.

Myocardial ischemia-reperfusion (MIR) injury is a major cause of adverse outcomes of revascularization after myocardial infarction. To identify the fundamental regulator of reperfusion injury, we performed metabolomics profiling in plasma of individuals before and after revascularization and identified a marked accumulation of arachidonate 12-lipoxygenase (ALOX12)-dependent 12-HETE following revascularization. The potent induction of 12-HETE proceeded by reperfusion was conserved in post-MIR in mice, pigs, and monkeys.

Potential Therapeutic Targeting of lncRNAs in Cholesterol Homeostasis.

Maintaining cholesterol homeostasis is essential for normal cellular and systemic functions. Long non-coding RNAs (lncRNAs) represent a mechanism to fine-tune numerous biological processes by controlling gene expression. LncRNAs have emerged as important regulators in cholesterol homeostasis.

The epitranscriptome of long noncoding RNAs in metabolic diseases.

Long noncoding RNAs (lncRNAs) have abundant content and extensive functions that regulate the expression of genes at multiple levels. Recently, transcriptome-wide analysis confirmed that RNA can undergo various chemical modifications in response to stimulation by the environment that further determine the action mechanisms of RNAs and expand the diversity of the transcriptome. Modifications that occur in lncRNAs can affect their expression and the regulation of downstream molecules by changing the secondary structure, splicing, degradation or molecular stability of lncRNAs.

LncRNA-modulated autophagy in plaque cells: a new paradigm of gene regulation in atherosclerosis?

The development of atherosclerosis is accompanied by the functional deterioration of plaque cells, which leads to the escalation of endothelial inflammation, abnormal vascular smooth muscle cell phenotype switching and the accumulation of lipid-laden macrophages within vascular walls. Autophagy, a highly conserved homeostatic mechanism, is critical for the delivery of cytoplasmic substrates to lysosomes for degradation. Moderate levels of autophagy prevent atherosclerosis by safeguarding plaque cells against apoptosis, preventing inflammation, and limiting the lipid burden, whereas excessive autophagy exacerbates cell damage and inflammation and thereby accelerates the formation of atherosclerotic plaques.

Sophoricoside ameliorates cardiac hypertrophy by activating AMPK/mTORC1-mediated autophagy.

Aim: The study aims to evaluate protective effects of sophoricoside (Sop) on cardiac hypertrophy. Meanwhile, the potential and significance of Sop should be broadened and it should be considered as an attractive drug for the treatment of pathological cardiac hypertrophy and heart failure.

Methods: Using the phenylephrine (PE)-induced neonatal rat cardiomyocytes (NRCMs) enlargement model, the potent protection of Sop against cardiomyocytes enlargement was evaluated.

Long non-coding RNA H19 in atherosclerosis: what role?

Atherosclerosis (AS) is widely accepted to be a multistep pathophysiological process associated with several other processes such as angiogenesis and inflammatory response. Long non-coding RNAs (lncRNAs) are non-protein coding RNAs (more than 200 nucleotides in length) and can regulate gene expression at the transcriptional and post-transcriptional levels. Recent studies suggest that lncRNA-H19 plays important roles in the regulation of angiogenesis, adipocyte differentiation, lipid metabolism, inflammatory response, cellular proliferation and apoptosis.

Ca-Dependent NOX5 (NADPH Oxidase 5) Exaggerates Cardiac Hypertrophy Through Reactive Oxygen Species Production.

NOX5 (NADPH oxidase 5) is a homolog of the gp91 subunit of the phagocyte NOX, which generates reactive oxygen species. NOX5 is involved in sperm motility and vascular contraction and has been implicated in diabetic nephropathy, atherosclerosis, and stroke. The function of NOX5 in the cardiac hypertrophy is unknown.

Bilirubin in metabolic syndrome and associated inflammatory diseases: New perspectives.

Diabetes mellitus is one of the major global health issues, which is closely related to metabolic dysfunction and the chronic inflammatory diseases. Multiple studies have demonstrated that serum bilirubin is negatively correlated with metabolic syndrome and associated inflammatory diseases, including atherosclerosis, hypertension, etc. However, the roles of bilirubin in metabolic syndrome and associated inflammatory diseases still remain unclear.

Nonalcoholic Fatty Liver Disease: An Emerging Driver of Hypertension.

Hypertension, a multifactorial disorder resulting from the interplay between genetic predisposition and environmental risk factors, affects ≈30% of adults. Emerging evidence has shown that nonalcoholic fatty liver disease (NAFLD), as an underestimated metabolic abnormality, is strongly associated with an increased risk of incident prehypertension and hypertension. However, the role of NAFLD in the development of hypertension is still obscure and is highly overlooked by the general public.

Mangiferin promotes macrophage cholesterol efflux and protects against atherosclerosis by augmenting the expression of ABCA1 and ABCG1.

Mangiferin has been identified as a potent cardioprotective factor that enhances high-density lipoprotein cholesterol levels in plasma. The aim of this study was to investigate the impact of mangiferin on macrophage cholesterol efflux and the development of atherosclerosis. The results showed that mangiferin injection significantly decreased atherosclerotic plaque size, and reduced plasma levels of low-density lipoprotein cholesterol, triglyceride, and total cholesterol in apoE knockout mice, whereas reverse cholesterol transport efficiency and high-density lipoprotein cholesterol levels were enhanced.

Hepatic Interferon Regulatory Factor 6 Alleviates Liver Steatosis and Metabolic Disorder by Transcriptionally Suppressing Peroxisome Proliferator-Activated Receptor γ in Mice.

Nonalcoholic fatty liver disease (NAFLD) has become a worldwide epidemic. A large and growing unmet therapeutic need has inspired numerous studies in the field. Integrating the published genomic data available in the Gene Expression Omnibus (GEO) with NAFLD samples from rodents, we discovered that interferon regulatory factor 6 (IRF6) is significantly downregulated in high-fat diet (HFD)-induced fatty liver.

MicroRNA-296: a promising target in the pathogenesis of atherosclerosis?

Atherosclerosis has been recognized as an inflammatory disease involving the vascular wall. MicroRNAs are a group of small noncoding RNAs to regulate gene expression at the transcriptional level through mRNA degradation or translation repression. Recent studies suggest that miR-296 may play crucial roles in the regulation of angiogenesis, inflammatory response, cholesterol metabolism, hypertension, cellular proliferation and apoptosis.