Endothelial AGO1 Drives Vascular Inflammation and Atherosclerosis via a Non-Canonical Nuclear Mechanism.

Background: Endothelial cell (EC) dysfunction is both a cause and consequence of vascular inflammation and lipid dysregulation in atherosclerosis, yet the molecular drivers linking EC dysfunction to systemic metabolic derangements remain incompletely understood. We previously identified Argonaute 1 (AGO1)-a canonical component of the RNA-induced silencing complex-as a regulator of EC function in angiogenesis and metabolism. In this study, we uncover a previously unrecognized, non-canonical role of nuclear AGO1 in ECs as a transcriptional coactivator of NF-κB, and demonstrate that EC-specific AGO1 inhibition simultaneously improves lipid metabolism, liver function, and vascular inflammation, thereby attenuating atherosclerosis.

Single-Cell Metabolic Imaging Reveals Glycogen Driven-Adaptations in Endothelial Cells.

Endothelial dysfunction (ED) is a defining feature of diabetes mellitus (DM) and a key contributor to many metabolic and cardiovascular diseases. Endothelial cells (ECs) are known to be highly glycolytic and primarily rely on glucose to meet their energy demands. However, the role of glycogen metabolism in ECs remains poorly characterized due to a lack of suitable tools.

METTL3 mediates atheroprone flow-induced glycolysis in endothelial cells.

Atheroprone flow-increased glycolysis in vascular endothelial cells (ECs) is pivotal in EC dysfunction and the initiation of atherosclerosis. Methyltransferase 3 (METTL3) is a major mA methyltransferase for RNA N6-mehtyladenosine (mA) modifications to regulate epitranscriptome and cellular functions. With the atheroprone flow upregulating METTL3 and mA RNA hypermethylation, we investigate the role of METTL3 in atheroprone flow-induced glycolysis in ECs in vitro and in vivo.

Role of long noncoding RNAs in diabetes-associated peripheral arterial disease.

Diabetes mellitus (DM) is a metabolic disease that heightens the risks of many vascular complications, including peripheral arterial disease (PAD). Various types of cells, including but not limited to endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and macrophages (MΦs), play crucial roles in the pathogenesis of DM-PAD. Long non-coding RNAs (lncRNAs) are epigenetic regulators that play important roles in cellular function, and their dysregulation in DM can contribute to PAD.

Mapping Endothelial-Macrophage Interactions in Diabetic Vasculature: Role of TREM2 in Vascular Inflammation and Ischemic Response.

Diabetes mellitus (DM) significantly accelerates vascular diseases like peripheral arterial disease (PAD). Endothelial cells (ECs) and macrophages (MΦs) singularly and synergistically are important contributors to DM-associated vascular dysfunction. Single-cell (sc) profiling technologies are revealing the true heterogeneity of ECs and MΦs, but how this cellular diversity translates to cell-cell interactions, and consequentially vascular function, remains unknown.

Regulation of nuclear transcription by mitochondrial RNA in endothelial cells.

Chromatin-associated RNAs (caRNAs) form a relatively poorly recognized layer of the epigenome. The caRNAs reported to date are transcribed from the nuclear genome. Here, leveraging a recently developed assay for detection of caRNAs and their genomic association, we report that mitochondrial RNAs (mtRNAs) are attached to the nuclear genome and constitute a subset of caRNA, thus termed mt-caRNA.

Downregulation of hepatic lncRNA Gm19619 improves gluconeogenesis and lipogenesis following vertical sleeve gastrectomy in mice.

Long non-coding RNAs (lncRNAs) are emerging important epigenetic regulators in metabolic processes. Whether they contribute to the metabolic effects of vertical sleeve gastrectomy (VSG), one of the most effective treatments for sustainable weight loss and metabolic improvement, is unknown. Herein, we identify a hepatic lncRNA Gm19619, which is strongly repressed by VSG but highly up-regulated by diet-induced obesity and overnight-fasting in mice.

Long noncoding RNA LEENE promotes angiogenesis and ischemic recovery in diabetes models.

Impaired angiogenesis in diabetes is a key process contributing to ischemic diseases such as peripheral arterial disease. Epigenetic mechanisms, including those mediated by long noncoding RNAs (lncRNAs), are crucial links connecting diabetes and the related chronic tissue ischemia. Here we identify the lncRNA that enhances endothelial nitric oxide synthase (eNOS) expression (LEENE) as a regulator of angiogenesis and ischemic response.

Vascular Regulation by Super Enhancer-Derived LINC00607.

Vascular endothelial cells (ECs) play a pivotal role in whole body homeostasis. Recent advances have revealed enhancer-associated long non-coding RNAs (lncRNAs) as essential regulators in EC function. We investigated LINC00607, a super enhancer-derived lncRNA (SE-lncRNA) in human arteries with an emphasis on ECs.