YAP-mediated macrophage polarization is involved in progression of atherosclerosis

Xin Zhang1, Xia Sun2, Qiaohong Qin1

  • 1Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, Shaanxi, 710021, China.

PubMed
Abstract

Insights

Yes-associated protein (YAP) promotes atherosclerosis by driving M1 macrophage polarization via CD36 upregulation. Inhibiting YAP in macrophages offers a potential therapeutic strategy for atherosclerosis.

Area of Science:

  • Cardiovascular Biology
  • Immunology
  • Molecular Medicine

Background:

  • Macrophage polarization is a key factor in the development of atherosclerosis.
  • Yes-associated protein (YAP) influences macrophage polarization, but its specific role in atherosclerosis is not fully understood.

Purpose of the Study:

  • To investigate the role of YAP-mediated macrophage polarization in atherosclerosis.
  • To explore YAP as a potential therapeutic target for atherosclerosis.

Main Methods:

  • Atherosclerosis was induced in mice using a high-cholesterol diet and AAV8-mPCSK9 injection.
  • Mice with macrophage-specific YAP deletion (YAPΔMɸ) and ApoE-/- mice were utilized.
  • Adeno-associated virus (AAV)-mediated delivery of shRNA targeting YAP in macrophages was employed for therapeutic evaluation.

Main Results:

  • Macrophage-specific YAP deletion reduced atherosclerotic plaque size and promoted M2 macrophage polarization.
  • YAP overexpression reversed these effects, indicating YAP promotes atherosclerosis.
  • YAP upregulated CD36 expression via TEAD4, enhancing oxidized low-density lipoprotein (ox-LDL) uptake and M1 polarization.
  • Macrophage-specific YAP knockdown significantly mitigated atherosclerosis in ApoE-/- mice.

Conclusions:

  • YAP promotes atherosclerosis by inducing M1 macrophage polarization through CD36 upregulation via TEAD4.
  • Targeting YAP in macrophages presents a promising therapeutic avenue for atherosclerosis treatment.

Related Concept Videos

Inflammation01:38

Inflammation

Overview
61.5K
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...
853
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...
355
Peripheral Artery Disease I: Introduction01:30

Peripheral Artery Disease I: Introduction

Peripheral artery disease (PAD) predominantly results from atherosclerosis, which involves the accumulation of fatty deposits, or plaques, within the walls of arteries. This causes them to narrow and harden, significantly reducing blood flow. PAD predominantly affects the legs, particularly the arteries supplying the thighs and calves. In rare cases, it may involve other arteries, including those in the arms.Etiology of PAD:The principal cause of PAD is atherosclerosis, which results from fatty...
295
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...
307