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Review
. 2025 Jun 26:12:1613900.
doi: 10.3389/fcvm.2025.1613900. eCollection 2025.

Molecular crosstalk in perivascular adipose tissue: mechanisms of inflammation, metabolic dysregulation, and therapeutic opportunities in cardiovascular disease

Shunhong Zhang  1 , Jun Jiang  1 , Yi Luo  1 , Guangyue Liu  2 , Saidi Hu  3 , Siran Wan  4 , Chenchen Luo  5 , Hong Li  6 , Nian Li  7 , Jailson da Graça Espírito Santo Vasconcelos  8 , Leonilde Lavres Ceita de Carvalho  8 , Monazeri Lima Bragança da Costa  9 , José Etchu Takounjou  8 , Karem Maimite Das Neves  8 , Luzimery Dos Ramos da Conceição  8 , Marinela da Costa Encarnação  8 , Lin-Yong Zhao  10
Affiliations
Review

Molecular crosstalk in perivascular adipose tissue: mechanisms of inflammation, metabolic dysregulation, and therapeutic opportunities in cardiovascular disease

Shunhong Zhang et al. Front Cardiovasc Med. .

Abstract

The escalating recognition of perivascular adipose tissue (PVAT) as a molecular nexus in cardiovascular disease (CVD) pathogenesis necessitates a comprehensive synthesis of its spatiotemporal dynamics and therapeutic potential. This review synthesizes PVAT's roles in vascular inflammation, metabolic dysregulation, and emerging diagnostic strategies, emphasizing molecular cross-talk and spatial heterogeneity. We explore PVAT's molecular interactions in obesity, diabetes, and hypertension, elucidating its contribution to inflammation, oxidative stress, and endothelial dysfunction. Advanced imaging techniques, notably the perivascular fat attenuation index (FAI) and circulating biomarkers, are highlighted for early CVD detection. Novel therapeutic strategies, including lifestyle modifications, pharmacological interventions, and gut microbiota modulation, are discussed. Finally, we emphasize multi-omics approaches and propose a roadmap bridging basic and clinical research to advance PVAT-based CVD management.

Keywords: atherosclerosis; biomarkers; cardiovascular disease; perivascular adipose tissue; vascular inflammation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) The cellular composition of perivascular adipose tissue (PVAT) includes adipocytes, macrophages(M2), neutrophils, dendritic cells, mast cells, eosinophils, T cells, B cells, and various other cell types. (B) Balance of anti-inflammatory and pro-inflammatory adipokines. (C) Leptin, resistin, RBP4, TNF-αand IL-6 can activate the JNK, NF-κB, and JAK-STAT pathways, leading to insulin resistance. (D) Pro-inflammatory factors contribute to endothelial cell dysfunction, as well as the migration of vascular smooth muscle cells and monocytes, ultimately leading to atherosclerosis. (E) The reduction of adiponectin, Ometin, and H2S, alongside the increase in TNF-α, IL-6, and resistin, contributes to increased arterial stiffness and vascular tone. This biochemical imbalance promotes the secretion of renin and activates the RAS system, ultimately resulting in hypertension.
Figure 2
Figure 2
Multidisciplinary research roadmap for PVAT.
See this image and copyright information in PMC

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