Related Experiment Video

Updated: Nov 1, 2025

A Human Ex Vivo Atherosclerotic Plaque Model to Study Lesion Biology
05:51

A Human Ex Vivo Atherosclerotic Plaque Model to Study Lesion Biology

Published on: May 6, 2014

13.4K

KLF5/LINC00346/miR‑148a‑3p axis regulates inflammation and endothelial cell injury in atherosclerosis

Fangfang Wang1, Jiyong Ge1, Shenglan Huang1

  • 1Department of Cardiovascular Disease, Changzhou No. 2 People's Hospital, Affiliated Nanjing Medical University, Changzhou, Jiangsu 213000, P.R. China.

International Journal of Molecular Medicine
|June 24, 2021
PubMed

Insights

Krüppel‑like factor 5 (KLF5) promotes atherosclerosis by upregulating LINC00346, which sponges miR‑148a‑3p. KLF5 interference inhibits inflammation and injury in oxidized low‑density lipoprotein‑stimulated cells by upregulating miR‑148a‑3p.

Area of Science:

  • Cardiovascular Biology
  • Molecular Biology
  • Cell Biology

Background:

  • Atherosclerosis (AS) is a primary cause of cardiovascular diseases, linked to significant morbidity and mortality.
  • Understanding the molecular mechanisms underlying AS is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the role of the Krüppel‑like factor 5 (KLF5)/LINC00346/miR‑148a‑3p regulatory loop in the pathogenesis of AS.
  • To elucidate the molecular interactions within this pathway in response to oxidized low‑density lipoprotein (OX‑LDL) stimulation.

Main Methods:

  • Quantitative real‑time PCR (RT‑qPCR) to measure KLF5, LINC00346, and miR‑148a‑3p expression.
  • Western blot analysis for KLF5, phosphorylated eNOS (p‑eNOS), and eNOS protein levels.
  • ELISA kits to assess inflammatory cytokines (TNF‑α, IL‑1β, IL‑6) and nitric oxide (NO) levels.
  • Chromatin immunoprecipitation (ChIP)‑PCR and luciferase reporter assays to confirm molecular interactions.

Main Results:

  • KLF5 expression was elevated in AS patients' serum and OX‑LDL‑stimulated human umbilical vein endothelial cells (HUVECs).
  • KLF5 directly promoted LINC00346 transcription, and LINC00346 acted as a molecular sponge for miR‑148a‑3p.
  • KLF5/LINC00346 interference or miR‑148a‑3p overexpression reduced inflammatory responses and endothelial cell injury.
  • miR‑148a‑3p was found to target and downregulate KLF5 expression.

Conclusions:

  • The KLF5/LINC00346/miR‑148a‑3p axis plays a significant role in AS development.
  • KLF5 promotes AS by upregulating LINC00346 and consequently inhibiting miR‑148a‑3p, leading to inflammation and endothelial dysfunction.
  • Interfering with KLF5 or LINC00346, or enhancing miR‑148a‑3p, offers potential therapeutic strategies for AS.

Keywords:
KLF5LINC00346atherosclerosisendothelial cellsfunction injuryinflammationmiR‑148a‑3p

More Related Videos

Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response12:50

Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response

Published on: September 15, 2017

6.7K
Using En Face Immunofluorescence Staining to Observe Vascular Endothelial Cells Directly06:09

Using En Face Immunofluorescence Staining to Observe Vascular Endothelial Cells Directly

Published on: August 20, 2019

16.1K

Related Concept Videos

Inflammation01:38

Inflammation

Overview
56.9K
Atherosclerosis I: Introduction01:30

Atherosclerosis I: Introduction

Atherosclerosis is a progressive disorder characterized by the buildup of plaques on the arterial inner wall, causing them to narrow and harden over time. These plaques comprise lipids, calcium, blood components, carbohydrates, and fibrous tissue. The process primarily affects the intima of large and medium-sized arteries, reducing blood flow in any artery.Etiology and risk factorsThe cause of atherosclerosis is multifactorial, involving a complex interplay among endothelial injury, lipid...
283
Atherosclerosis III: Management01:26

Atherosclerosis III: Management

Management of atherosclerosis involves an integrated strategy encompassing pharmacological treatment, surgical interventions, lifestyle changes, and nutrition therapy to address the multifactorial nature of the disease.Pharmacological TherapyA cornerstone of atherosclerosis management is the use of pharmacological agents. Statins, such as atorvastatin, are pivotal in inhibiting HMG-CoA reductase, an enzyme that catalyzes an initial step in cholesterol synthesis in the liver. This reduction in...
87
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
8.0K
Coronary Artery Disease II: Pathophysiology01:26

Coronary Artery Disease II: Pathophysiology

Coronary Artery Disease (CAD) originates from a series of events that impair the function of coronary arteries, the blood vessels responsible for delivering oxygen-rich blood to the heart muscle. The pathophysiology of CAD is closely linked to atherosclerosis, a chronic inflammatory and lipid-driven condition affecting the vascular endothelium.1. Endothelial DamageThe process begins with damage to the vascular endothelium, which serves as a protective barrier between the blood and the vessel...
125
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...
3.0K