Endothelial miRNAs as Cellular Messengers in Cardiometabolic Diseases

Endothelial dysfunction is a prominent feature of cardiometabolic diseases and contributes to the prothrombotic and proinflammatory state of the vasculature. Endothelial cells secrete miRNAs to communicate with other cells in the cardiovascular system. Endothelial cells can also take up miRNAs secreted by other cell types and this modulates endothelial cell biology. Circulating miRNAs can be utilized as biomarkers of cardiovascular and metabolic diseases and extracellular vesicles could potentially be harnessed for the delivery of therapeutics such as miRNAs, to control cardiometabolic diseases including metabolic syndrome, diabetes, and atherosclerosis. Metabolic syndrome is a clustering of risk factors that increases susceptibility to serious cardiometabolic complications, including type 2 diabetes (T2D) and myocardial infarction. Understanding the underlying mechanisms will advance the development of diagnostic and therapeutic approaches. A prominent feature of cardiometabolic diseases is endothelial dysfunction. Endothelial cell (EC) homeostasis and response to pathological stimuli are controlled by gene regulatory networks in which miRNAs play a critical role. Recently, miRNAs have been implicated as cell–cell messengers that can influence cellular function. This review investigates the known and potential roles for miRNA-based cell–cell communication in the control of cardiovascular health and explores the value of identifying miRNA biomarkers and developing therapeutics that harness or antagonize miRNA-based communication. Metabolic syndrome is a clustering of risk factors that increases susceptibility to serious cardiometabolic complications, including type 2 diabetes (T2D) and myocardial infarction. Understanding the underlying mechanisms will advance the development of diagnostic and therapeutic approaches. A prominent feature of cardiometabolic diseases is endothelial dysfunction. Endothelial cell (EC) homeostasis and response to pathological stimuli are controlled by gene regulatory networks in which miRNAs play a critical role. Recently, miRNAs have been implicated as cell–cell messengers that can influence cellular function. This review investigates the known and potential roles for miRNA-based cell–cell communication in the control of cardiovascular health and explores the value of identifying miRNA biomarkers and developing therapeutics that harness or antagonize miRNA-based communication. according to the National Institutes of Health, ‘a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or biological responses to a therapeutic intervention’. Circulating biomarkers can be sampled in the blood and used to diagnose disease, monitor response to treatment, or provide prognostic information about the likely progression of disease. Since measuring circulating miRNAs is noninvasive and miRNAs are able to fulfill numerous criteria that constitute an ideal biomarker (such as sensitivity, specificity, predictability, and robustness), several groups have reported the use of miRNAs as diagnostic or prognostic biomarkers of cardiometabolic diseases. membrane-encapsulated vesicles released by cells into the extracellular space. EVs are classified into three subpopulations according to their size, subcellular origin, and release pathway: exosomes, MVs, and ABs. Exosomes (<150 nm) are generated inside multivesicular bodies (MVBs) of the endosomal compartment and secreted into the extracellular space by the fusion of MVBs with the plasma membrane. By contrast, MVs (100–1000 nm) are produced by budding and fission of the plasma membrane. ABs, generated during the late steps of apoptosis by blebbing of the plasma membrane, are the largest EVs at 1–5 μm. While exosomes are constitutively released by cells, MVs are predominantly released from activated or apoptotic cells. EVs contain numerous bioactive molecules, such as nucleic acids (e.g., miRNAs, lncRNAs), specific proteins, and lipids and play an important role in intercellular communication. a constellation of metabolic dysfunctions, characterized by abdominal obesity, dyslipidemia, hyperglycemia, insulin resistance, and/or hypertension, that collectively increase the risk of developing cardiovascular diseases (approximately threefold) and T2D (approximately fivefold). RNA molecules that are not translated into protein products. Diverse classes of ncRNA [e.g., miRNAs, ceRNAs, eRNAs, piwi-interacting RNAs, lncRNAs, circular RNAs (circRNAs)] have emerged as key regulators of gene expression and cellular homeostasis. Recent studies have highlighted the critical role of dysregulated ncRNAs in the emergence of pathological processes occurring during cardiometabolic diseases. a chronic metabolic disorder characterized by the body being unable to metabolize glucose, resulting in high circulating blood glucose levels (hyperglycemia) that over time may promote the development of cardiovascular diseases. T2D is due to the development of resistance to the cellular effects of insulin and/or or being unable to produce sufficient insulin.