The PVAT-MAMs Axis in Atherosclerosis: A Hypothesis-Driven Cross-Scale Conceptual Framework

Area of Science:

• Cardiovascular Research
• Metabolic Syndrome
• Cellular Biology

Background:

• Atherosclerosis (AS) is a leading cause of cardiovascular disease, but its complexity and link to metabolic disorders exceed current models.
• The "endothelial injury-lipid deposition-inflammatory amplification" paradigm does not fully explain AS clinical heterogeneity.

Purpose of the Study:

• Introduce the perivascular adipose tissue-mitochondria-associated endoplasmic reticulum membranes (PVAT-MAMs) axis as a conceptual framework.
• Link metabolic dysfunction in PVAT to intracellular stress in vascular cells for AS pathogenesis.
• Propose a novel perspective on AS heterogeneity and potential therapeutic strategies.

Main Methods:

• Review and synthesis of existing experimental and associative evidence.
• Development of a hypothesis-driven, cross-scale conceptual framework (PVAT-MAMs axis).
• Analysis of proposed mechanisms linking PVAT dysfunction to MAMs perturbation.

Main Results:

• Metabolic stress in PVAT may release mediators affecting MAMs.
• Perturbation of MAMs is associated with dysregulated calcium handling, lipid metabolism, and inflammation in AS.
• The PVAT-MAMs axis offers an integrative view of AS progression.

Conclusions:

• The PVAT-MAMs axis provides a novel conceptual model for understanding AS heterogeneity.
• This framework highlights potential pathogenic nodes from PVAT to MAMs.
• Further experimental validation is required to establish causal relationships and therapeutic potential.