Myeloid GRK2 Regulates Obesity-Induced Endothelial Dysfunction by Modulating Inflammatory Responses in Perivascular...

Area of Science:

• Vascular biology
• Endocrinology
• Obesity research

Background:

• Perivascular adipose tissue (PVAT) influences vascular health, particularly in obesity-associated diseases.
• Myeloid G protein-coupled receptor kinase 2 (GRK2) is implicated in modulating PVAT's role in vascular function.

Purpose of the Study:

• To investigate the role of myeloid GRK2 in PVAT-dependent vasodilation responses.
• To explore GRK2 as a potential therapeutic target for endothelial dysfunction in obesity.

Main Methods:

• Analysis of GRK2 expression in human PVAT samples.
• Utilizing myeloid-specific GRK2-deficient mice (LysM-GRK2+/-) fed a high-fat diet (HFD).
• Assessing endothelium-dependent vasodilation, immune cell infiltration, and inflammatory marker expression (TNFα, Nox1).

Main Results:

• GRK2 expression in PVAT correlates with immune markers and leptin in patients with abdominal aortic aneurysms.
• GRK2 deficiency in myeloid cells preserves endothelium-dependent vasodilation in HFD-fed mice.
• Reduced GRK2 attenuates macrophage/T lymphocyte infiltration and TNFα/Nox1 induction in PVAT.
• Pharmacological inhibition of TNFα or Nox pathways rescues impaired vasodilation.

Conclusions:

• Myeloid GRK2 is a critical mediator of HFD-induced endothelial dysfunction via PVAT.
• Targeting myeloid GRK2 offers a potential therapeutic strategy for obesity-related vascular complications.