Decoding intercellular communication network in venous malformations

Xiao-Le Wang; Ye-Xin Yue; Ying Xie; Yang Yang; Gang Chen; Jian Li; Hou-Fu Xia

doi:10.1016/j.jpha.2026.101626

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Xiao-Le Wang, Ye-Xin Yue, Ying Xie, Yang Yang, Gang Chen, Jian Li, Hou-Fu Xia. Decoding intercellular communication network in venous malformations[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101626

Citation:

Xiao-Le Wang, Ye-Xin Yue, Ying Xie, Yang Yang, Gang Chen, Jian Li, Hou-Fu Xia. Decoding intercellular communication network in venous malformations[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101626

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Decoding intercellular communication network in venous malformations

doi: 10.1016/j.jpha.2026.101626

Xiao-Le Wang^a,b,
Ye-Xin Yue^a,
Ying Xie^a,
Yang Yang^a,
Gang Chen^a,b,c,d,
Jian Li^{a,b
,
,},
Hou-Fu Xia^{a,b
,
,}

a. State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China;
b. Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, China;
c. TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, China;
d. Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, 430071, China

Funds:

This work was supported by the National Natural Science Foundation of China (Grant Nos.: 82101036, 82403454, and 82341023), and the Innovative Research Team of High-level Local Universities in Shanghai (SHSMU-ZLCX20212300).

Received Date: Oct. 26, 2025
Accepted Date: Apr. 01, 2026
Rev Recd Date: Apr. 01, 2026
Available Online: Apr. 03, 2026

Abstract

Abstract

Venous malformations (VMs) are common congenital vascular anomalies that usually appear at birth or in childhood. Mutations in the tyrosine kinase with immunoglobulin-like and epidermal growth factor like (EGF-like) domains 2/phosphoinositide 3-kinase (TIE2/PI3K)-related genes within endothelial cells (ECs) disrupt EC function and phenotype. However, VMs do not merely manifest as abnormalities of ECs. Lesions typically feature dilated and tortuous vessels with stagnant blood flow, thrombi or phleboliths, and disorganized structural layers. Histological evidence shows that VMs involve a range of cellular and noncellular components, including ECs, vascular smooth muscle cells, immune cells, platelets, and the extracellular matrix. While gene mutations in ECs may pull the trigger, VM progression depends on complex interactions among various elements, complicating clinical management. Existing studies have identified individual clues (e.g., mutations, cell loss, matrix degradation). However, the failure to define the interlocking logic between these pieces has prevented the assembly of a coherent picture on VM pathophysiology. Developmental biology reveals that embryonic angiogenesis is governed by ECs through tightly regulated intercellular communication. Hijacking of this communication is increasingly recognized as key contributors to VM development. This review maps how intercellular communication—via secretory factors, extracellular vesicles, direct contact, and mechanobiology—coalesces into a cohesive network that drives VM progression, and evaluates these pathways as promising diagnostic and therapeutic targets.
- Intercellular communication,
- Secretory factors,
- Extracellular vesicles,
- Direct contact,
- Mechanobiology,
- Therapy

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