Posts Tagged: microRNA

MicroRNAs for Restenosis and Thrombosis After Vascular Injury

MicroRNAs for Restenosis and Thrombosis After Vascular Injury

Clarice Gareri, Salvatore De Rosa, Ciro Indolfi

The cartoon represents the hypothetical structure of a vascular scaffold able to elute microRNAs (miRNAs). The scaffold (blue) is coated by poly-lactic-co-glycolic acid (PLGA) (green). At the bottom of the figure, the most promising miRNAs to be modulated for therapeutic use are listed. [Powerpoint File]

MicroRNAs for Restenosis and Thrombosis After Vascular Injury

MicroRNAs for Restenosis and Thrombosis After Vascular Injury

Clarice Gareri, Salvatore De Rosa, Ciro Indolfi

The figure illustrates specific vascular (upper section) or platelet-derived (lower section) microRNAs that can be measured in the flowing bloodstream. [Powerpoint File]

MicroRNAs for Restenosis and Thrombosis After Vascular Injury

MicroRNAs for Restenosis and Thrombosis After Vascular Injury

Clarice Gareri, Salvatore De Rosa, Ciro Indolfi

Schematic representation of the most relevant microRNAs (miRNAs) that modulate vascular smooth muscle cell (VSMCs) proliferation, with their direct molecular targets. The red area includes miRNAs that inhibit VSMCs proliferation (thus preventing ISR), whereas the green area indicates miRNAs that promote the synthetic phenotype of VSMCs. BMPR2 indicates bone morphogenetic protein receptor type II; Cdc-42, cell division control protein 42; FOXO4, Forkhead box protein O4; KLF-4, Kruppel-like factor 4; KLF-5, Kruppel-like factor 5; PTEN, phosphatase and tensin homolog; SMAD3, small mother against decapentaplegic; uPA, urokinase-type plasminogen activator; and WWP1, NEDD4-like E3 ubiquitin-protein ligase. [Powerpoint File]

MicroRNAs for Restenosis and Thrombosis After Vascular Injury

MicroRNAs for Restenosis and Thrombosis After Vascular Injury

Clarice Gareri, Salvatore De Rosa, Ciro Indolfi

Representative case of arterial restenosis, observed by means of intravascular optical coherence tomography (OCT). The picture shows a human artery with intimal hyperplasia 2 years after PCI with implantation of a coronary scaffold (struts-remnants indicated by yellow arrows). A thick neointimal layer is evident at the adluminal side of the struts-remnants (neointimal area included between the yellow dotted line and the green line). [Powerpoint File]

MicroRNAs and Cardiac Regeneration

MicroRNAs and Cardiac Regeneration

Conrad P. Hodgkinson, Martin H. Kang*, Sophie Dal-Pra*, Maria Mirotsou, Victor J. Dzau

MicroRNAs (miRNAs/miR) and reprogramming. miRNAs promote the generation of cardiomyocytes via several mechanisms. Fibroblasts (FB) can be reprogrammed into cardiomyocytes (CM) by miRNAs directly or through an intermediate inducible pluripotent stem (iPSC) state. miRNAs also promote cardiac progenitor cell (CPC) and embryonic stem cell (ESC) cardiac differentiation. miRNAs can promote or inhibit cardiomycyte proliferation. [Powerpoint File]

MicroRNA Regulation and Cardiac Calcium Signaling: Role in Cardiac Disease and Therapeutic Potential

MicroRNA Regulation and Cardiac Calcium Signaling: Role in Cardiac Disease and Therapeutic Potential

Masahide Harada*, Xiaobin Luo*, Toyoaki Murohara, Baofeng Yang, Dobromir Dobrev, Stanley Nattel

Strategies for microRNA (miRNA) therapeutics. Under a specific pathological condition, the expression of a targeted miRNA could be either upregulated or downregulated. Where the targeted miRNA is upregulated, miRNA knockdown techniques could be used, including miRNA antisense oligonucleotides, miRNA sponges, and miRNA erasers. When a targeted miRNA is downregulated, this decrease can be corrected by delivering a synthetic miRNA mimic or tissue-specific viruses overexpressing the miRNA. The goal of both miRNA knockdown and overexpression techniques is to restore the targeted miRNA to its normal level, suppressing the pathological consequences of miRNA dysregulation. ORF indicates open reading frame. [Powerpoint File]

MicroRNA Regulation and Cardiac Calcium Signaling: Role in Cardiac Disease and Therapeutic Potential

MicroRNA Regulation and Cardiac Calcium Signaling: Role in Cardiac Disease and Therapeutic Potential

Masahide Harada*, Xiaobin Luo*, Toyoaki Murohara, Baofeng Yang, Dobromir Dobrev, Stanley Nattel

Biogenesis and actions of microRNAs (miRNAs). Under the control of transcription factors and RNA-polymerase II, intergenic miRNAs are transcribed via their own promoter regions, whereas transcription of intragenic miRNAs is regulated by promoters of their host-protein–coding genes. The primary miRNA transcript (pri-miRNA) folds into single or multiple stem–loop structures, which are further processed into short hairpin intermediates called precursor miRNA (premiRNA). Intergenic premiRNAs are processed by the RNase III-endonuclease Drosha, together with the double-stranded RNA–binding-protein DiGeorge syndrome critical region 8, whereas exonic and intronic miRNAs require the additional help of spliceosomes and debranching enzymes. Pre-miRNAs are translocated from the nucleus into the cytosol via the nuclear export protein, Exportin 5. In the cytoplasm, premiRNAs are further trimmed by another RNase III-endonuclease, Dicer, producing mature miRNA-duplexes. The mature miRNA-duplex becomes functional on incorporation of the seed strand (after its dissociation from the passenger strand), along with argonaute protein, into an RNA silencing complex (RISC). The miRNA–RISC complex binds to complementary binding sequences within the 3′-untranslated region of the target gene, to block translation of the encoded protein. When there is perfect complementarity, mRNA degradation also occurs, reducing mRNA-expression of the targeted transcript. ORF indicates open reading frame; Pre-miRNA, precursor miRNA; Pri-miRNA, primary transcript of miRNA; RNA Pol II, RNA-polymerase II; RISC, RNA-induced silencing complex; and TF, transcription factor. [Powerpoint File]

Microvesicles as Cell–Cell Messengers in Cardiovascular Diseases

Microvesicles as Cell–Cell Messengers in Cardiovascular Diseases

Xavier Loyer, Anne-Clémence Vion, Alain Tedgui, Chantal M. Boulanger

Mechanisms involving extracellular vesicles in cell-to-cell communication. Once released, exosomes, microparticles, and apoptotic bodies target recipient cells and are able to transfer information (microRNAs, proteins, etc) by membrane fusion (1), endocytosis (2), or receptor-mediated binding (3). (Illustration credit: Ben Smith). [Powerpoint File]

Exosomes and Cardiac Repair After Myocardial Infarction

Exosomes and Cardiac Repair After Myocardial Infarction

Susmita Sahoo, Douglas W. Losordo

Biogenesis of and release of exosomes from multivesicular bodies (MVBs). Endosomes originate by inward invagination of plasma membrane and have inverted plasma membrane. At the time of exosome formation, endosome membrane invaginates again toward its lumen, forming exosomes with the same membrane orientation as the plasma membrane. Outer and inner plasma membranes are shown in red and green color, respectively. [Powerpoint File]

Exosomes and Cardiac Repair After Myocardial Infarction

Exosomes and Cardiac Repair After Myocardial Infarction

Susmita Sahoo, Douglas W. Losordo

A suggested hypothesis on the role of exosomes released from a damaged heart as a potential intercellular communicator. Exosomes can carry signaling molecules to activate local tissues (C indicates cardiomyocytes; E, endothelial cells; F, fibroblasts; and S, stem cells) and distant organs such as bone marrow (BM). Furthermore, the exosomes released from progenitor cells and the reprogrammed BM can reprogram the ischemic tissues of the heart, inducing protection and regeneration (illustration credit: Ben Smith). [Powerpoint File]

MicroRNA Control of High-Density Lipoprotein Metabolism and Function

MicroRNA Control of High-Density Lipoprotein Metabolism and Function

Katey J. Rayner, Kathryn J. Moore

MicroRNA (miRNA) coordination of high-density lipoprotein (HDL) homeostasis. miRNAs have been shown to regulate genes involved in cholesterol efflux and HDL homeostasis in various tissues, including the liver, intestine, and macrophage. These miRNAs repress mRNA and protein expression of their target genes as indicated. In the liver, ATP-binding cassette transporter A1 (ABCA1) is a target of a number of miRNAs that reduce cholesterol efflux to lipid-poor apolipoprotein A-I (apoA-I), which generates nascent HDL. Free cholesterol on nascent HDL particles is then esterified to cholesteryl esters by lecithin-cholesterol acyltransferase (LCAT), converting nascent HDL to mature HDL. In peripheral tissues, ABCG1 mediates cholesterol transfer to mature HDL and is a target of miR-33, as well as miR-10b, whose expression is affected by the microbiome. Secreted miRNAs, such as miR-223, miR-92a, and miR-126, are carried on circulating HDL particles and may mediate extracellular signaling by repressing genes in target tissues. HDL interaction with macrophages and endothelial cells may result in miRNA exchange (ie, pick-up or delivery) although this remains an area of open investigation. On its return to the liver, HDL’s cholesterol and miRNA cargo is selectively taken up by scavenger receptor B-I (SR-BI), and excess cholesterol is excreted from the liver into the bile. Targeting of SR-BI and the ABC11 and ATP8B1 transporters reduce cholesterol hepatic clearance and excretion. Illustration credit: Ben Smith. [Powerpoint File]

Heart Failure Compendium: Non-coding RNAs in Cardiac Remodeling and Heart Failure

Heart Failure Compendium: Non-coding RNAs in Cardiac Remodeling and Heart Failure

Regalla Kumarswamy, Thomas Thum

Putative sources of circulating microRNAs (miR/miRNA). MiRNAs in circulation may originate from apoptotic or necrotic cells, secretory vesicles such as exosomes or microvesicles. In addition, they can also be secreted in free form by some unknown mechanisms. HDL indicates high-density lipoprotein. Illustration Credit: Ben Smith. [Powerpoint File]

Heart Failure Compendium: Non-coding RNAs in Cardiac Remodeling and Heart Failure

Heart Failure Compendium: Non-coding RNAs in Cardiac Remodeling and Heart Failure

Regalla Kumarswamy, Thomas Thum

MicroRNAs (miR/miRNA) that influence calcium and nuclear factor of activated T cells (NFAT) signaling in the heart. ANP indicates atrial natriuretic peptide; BNP, brain natriuretic peptide; CACNA1C, calcium channel, voltage-dependent, L-type, α1C; CamK, calmodulin kinase; CN, calcineurin; ET1, endothelin-1; Dyrk, dual specificity tyrosine phosphorylation–regulated kinase; GSK, glycogen synthase kinase; LTCC, L-type calcium channel; MHC, myosin heavy chain; NCX1, sodium–calcium exchanger; and SERCA2a, sarcoplasmic reticulum Ca2+-ATPase. Illustration Credit: Ben Smith. [Powerpoint File]

MicroRNAs and Stem Cells: Control of Pluripotency, Reprogramming, and Lineage Commitment

MicroRNAs and Stem Cells: Control of Pluripotency, Reprogramming, and Lineage Commitment

Eva-Marie Heinrich, Stefanie Dimmeler

MicroRNAs (miRs) in cardiovascular lineage commitment. Some miRs have been shown to directly control lineage commitment, whereas the majority of miRs control the functional maturation of the differentiated cells. Arrows indicate regulation during differentiation. [Powerpoint File]

Differential Expression of MicroRNAs in Different Disease States

Differential Expression of MicroRNAs in Different Disease States

Maha Abdellatif

A diagram showing microRNAs (miRNA) and their targets in cardiac hypertrophy. The diagram displays the different miRNAs and their targets that are involved in gene switching, cellular hypertrophy, fibrosis, and electric remodeling during cardiac hypertrophy. Upregulation or downregulation of a specific miRNA is represented by an upward (black) or a downward (red) arrow, respectively. The change in the expression levels of target genes inversely correlates with that of the targeting miRNA and is similarly represented by an up arrow or down arrow. All listed targets have been validated. The listed targets include thyroid hormone receptor-associated protein 1 (Thrap1), SRY-box containing gene 6 (Sox6), thyroid hormone receptor beta (Thrb), calmodulin, myocyte enhancer factor 2A (Mef2a), insulin-like growth factor-1 (IGF1), myostatin, muscle-specific RING finger protein-1 (MuRF1), dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A (Dyrk1a), sprouty 2/4 (SPRY2/4), connective tissue growth factor (CTGF), collagen IA1 (Col1A1), GATA-binding protein-4 (GATA4), phospholipase C beta 1 (PLCβ1), protein phosphatase 2, regulatory subunit B (B56) alpha isoform (Ppp2r5a), protein phosphatase 2 catalytic subunit (PP2Ac), and the indirect targets alpha and beta myosin heavy chain (αMyh and βMyh). [Powerpoint File]