Related Experiment Video

Updated: Nov 4, 2025

Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice
09:06

Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice

Published on: February 20, 2019

8.5K

Pyk2/MCU Pathway as a New Target for Reversing Atherosclerosis

Yingzhen Zhang1,2, Xiaoli Yang1,3, Zhongzhong Li1

  • 1Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

Frontiers in Cell and Developmental Biology
|May 24, 2021
PubMed

Insights

The proline-rich tyrosine kinase 2 (Pyk2)/mitochondrial calcium uniporter (MCU) pathway is activated in atherosclerosis and hydrogen peroxide-induced endothelial cell damage. Inhibiting this pathway may offer a new therapeutic target for treating atherosclerosis.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Cellular Pathology

Background:

  • Atherosclerosis (AS) development involves vascular endothelial cell damage through poorly understood molecular mechanisms.
  • The proline-rich tyrosine kinase 2 (Pyk2) and mitochondrial calcium uniporter (MCU) pathway's role in AS is not fully elucidated.

Purpose of the Study:

  • To investigate the role of the Pyk2/MCU pathway in an atherosclerosis mouse model and H2O2-induced endothelial cell damage.
  • To explore the underlying molecular mechanisms of the Pyk2/MCU pathway in AS pathogenesis.

Main Methods:

  • Established an atherosclerosis mouse model using apolipoprotein E-knockout (ApoE-/-) mice on a high-fat diet.
  • Utilized human umbilical vein endothelial cells (HUVECs) subjected to hydrogen peroxide (H2O2) insult.
  • Employed short hairpin RNA (shRNA) to down-regulate Pyk2 expression and assessed the effects of rosuvastatin treatment.

Main Results:

  • Pyk2/MCU expression was significantly elevated in atherosclerotic mouse arteries and H2O2-treated HUVECs.
  • Down-regulation of Pyk2 protected HUVECs from H2O2-induced damage.
  • Rosuvastatin inhibited the Pyk2/MCU pathway, preserving calcium balance, reducing mitochondrial damage and reactive oxygen species, and preventing apoptosis in AS and H2O2 models.

Conclusions:

  • The Pyk2/MCU pathway is implicated in AS-related endothelial cell damage.
  • Targeting the Pyk2/MCU pathway presents a potential novel therapeutic strategy for atherosclerosis intervention.
Keywords:
ApoE–/– miceHUVECsPyk2/MCUatherosclerosismitochondrion

More Related Videos

Induction of Accelerated Atherosclerosis in Mice: The "Wire-Injury" Model05:35

Induction of Accelerated Atherosclerosis in Mice: The "Wire-Injury" Model

Published on: August 25, 2020

11.4K
Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes09:16

Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes

Published on: June 3, 2018

7.4K

Related Concept Videos

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...
89
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...
290
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...
135
Coronary Artery Disease I: Introduction01:30

Coronary Artery Disease I: Introduction

Coronary Artery Disease (CAD): An Overview with Scientific InsightsCoronary Artery Disease (CAD), often referred to as C-A-D, is a prevalent blood vessel disorder classified under the broader category of atherosclerosis. Atherosclerosis is a pathological process characterized by the hardening and narrowing of arteries due to the accumulation of atherosclerotic plaques. These plaques are composed of cholesterol, fatty substances, inflammatory cells, calcium, and fibrin, reducing blood flow to...
568
Atherosclerosis IV: Nursing Management01:23

Atherosclerosis IV: Nursing Management

Nursing management for a patient with arteriosclerosis involves a comprehensive approach focusing on lifestyle modification, disease monitoring, education, and symptomatic care. Here is an overview of effective nursing strategies:Assessment and Monitoring: Initial and ongoing assessments are crucial. Nurses must document the patient's medical history, including any hypertension, diabetes, hyperlipidemia, and other cardiovascular diseases. Assessments also cover family history and lifestyle...
111
Atherosclerosis II: Clinical Manifestations and Diagnostic Tests01:27

Atherosclerosis II: Clinical Manifestations and Diagnostic Tests

Atherosclerosis is a progressive disorder that leads to the thickening and narrowing of arterial walls due to plaque buildup. This condition can cause various symptoms depending on the arteries affected:Coronary Artery Disease (CAD): This condition affects the coronary arteries and may lead to chest pain (angina), shortness of breath (dyspnea), heart attacks, and other heart disease symptoms.Cerebrovascular Disease: This affects blood flow to the brain, causing transient ischemic attacks (TIAs)...
129