MicroRNA-181b-5p/HEY2 axis is involved in the progress of deep venous thrombosis via mediating vascular endothelial

Dawei Zhang1, Cheng Cheng2, Meiying Yang1

  • 1Department of Orthopedics, Zibo Central Hospital, Zibo, People's Republic of China.

PubMed
Abstract

Insights

Low levels of microRNA 181b-5p are linked to deep-venous thrombosis (DVT) and post-thrombotic syndrome (PTS). Restoring miR-181b-5p levels protects endothelial cells and may aid DVT diagnosis.

Area of Science:

  • Vascular Biology
  • Molecular Medicine
  • Biomarker Discovery

Background:

  • Deep-venous thrombosis (DVT) is a serious condition with post-thrombotic syndrome (PTS) as a frequent complication.
  • Understanding the molecular mechanisms underlying DVT progression is crucial for developing effective diagnostic and therapeutic strategies.

Purpose of the Study:

  • To investigate the role of microRNA 181b-5p (miR-181b-5p) in the development and progression of DVT.
  • To assess the diagnostic potential of miR-181b-5p for DVT and its association with PTS.
  • To elucidate the cellular mechanisms by which miR-181b-5p influences endothelial cell function.

Main Methods:

  • Quantification of miR-181b-5p levels in 150 patients with acute lower extremity DVT.
  • Analysis of diagnostic accuracy using ROC curves and survival analysis with K-M plots.
  • In vitro studies using human umbilical vein endothelial cells (HUVECs) to assess the impact of miR-181b-5p on cell viability, migration, apoptosis, and inflammatory responses.
  • Identification and functional validation of miR-181b-5p target genes.

Main Results:

  • Reduced miR-181b-5p expression was observed in DVT patients and correlated with a higher incidence of PTS.
  • miR-181b-5p demonstrated significant diagnostic value for DVT (AUC=0.948).
  • Overexpression of miR-181b-5p enhanced HUVEC viability and migration, suppressed apoptosis, and reduced the release of inflammatory and adhesion factors.
  • HEY2 was identified as a direct target of miR-181b-5p, and its overexpression reversed the protective effects of miR-181b-5p in HUVECs.

Conclusions:

  • miR-181b-5p is a promising biomarker for DVT diagnosis and predicting PTS development.
  • Modulating miR-181b-5p, potentially by targeting HEY2, can mitigate endothelial cell damage in DVT.
  • Further research into miR-181b-5p as a therapeutic target for DVT is warranted.

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K
Anticoagulant Drugs: Low-Molecular-Weight Heparins01:30

Anticoagulant Drugs: Low-Molecular-Weight Heparins

Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...
624
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.0K
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
2.6K
Extrinsic and Intrinsic Pathways of Hemostasis01:20

Extrinsic and Intrinsic Pathways of Hemostasis

Blood clotting or coagulation involves extrinsic and intrinsic pathways, which ultimately merge into the common pathway, forming a fibrin clot.
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which...
5.8K