{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPF4V1, also known as CXCL4L1, has been evaluated in genetic studies for its potential impact on inflammatory disease; for example, variants in the PF4V1 gene were examined in patients with cystic fibrosis, although no significant associations were observed with lung disease severity, suggesting that its role in pulmonary inflammation may be limited in that context."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural analyses have revealed that PF4V1 differs from the classical platelet factor‐4 (CXCL4) by three C-terminal amino acids. This subtle change results in lower affinity for glycosaminoglycans and an increased diffusibility, features that are believed to contribute to its potent anti‐angiogenic activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn comprehensive reviews, PF4V1 has been highlighted as a highly potent anti‑tumoral regulator. Its ability to inhibit angiogenesis makes it an attractive candidate for modulating tumor growth, as it not only impairs neovascularization but also modulates leukocyte recruitment toward an anti‑tumoral phenotype."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nInvestigations into the cellular receptors for CXCL4L1 have demonstrated that PF4V1 effectively interacts with variants of the CXCR3 receptor. This binding is critical to its capacity to displace related chemokines from endothelial cells and to mediate downstream anti‑angiogenic effects."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nComparative studies between PF4 and PF4V1 have shown that PF4V1 exhibits enhanced potency in suppressing angiogenesis and tumor growth. This differential activity underscores the functional importance of the modifications found in PF4V1 and supports its unique role in immune regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the cardiovascular arena, PF4V1 has been investigated as a biomarker associated with coronary artery disease. Although its exact functional contribution in heart disease remains to be fully elucidated, early clinical evaluations suggest that PF4V1 could serve as an indicator of vascular pathology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional research has confirmed that PF4V1 (CXCL4L1) is a highly effective anti‑angiogenic and anti‑tumor chemokine. Its distinct structural configuration compared to CXCL4 places it at the forefront of chemokine candidates with therapeutic potential in cancer treatment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nExperimental models have revealed that PF4V1 can cooperate with other endogenous anti‑angiogenic molecules—such as fibstatin—to inhibit both angiogenesis and lymphangiogenesis. This synergistic interaction contributes to reduced metastatic spread in tumor models, highlighting its potential in anti‑metastatic gene therapy strategies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther dissection of intracellular signaling has indicated that PF4V1 modulates key pathways in endothelial cells. Notably, PF4V1 can attenuate ERK phosphorylation, among other kinase activities, thereby limiting endothelial cell proliferation and migration, which are essential processes in new vessel formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of cancer, PF4V1 and its relative CXCL4 have been reviewed as potential biomarkers and therapeutic agents due to their strong anti‑angiogenic and immunomodulatory properties, offering promising avenues for targeted intervention in tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic studies in patients with type I diabetes have revealed that PF4V1 promoter variants, which are associated with increased gene expression, may activate anti‑inflammatory pathways in mesangial cells. This upregulation is linked to higher levels of key inhibitors of inflammation, suggesting a protective role against renal inflammation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn vascular remodeling, comparative analyses using human vascular smooth muscle cells have demonstrated that PF4V1 modulates cellular behavior differently from CXCL4. Whereas PF4V1 governs aspects of cellular homeostasis, only CXCL4 robustly promotes proliferation and calcification, underlining the distinct physiological roles of these chemokines in vascular biology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, emerging findings indicate that PF4V1 can participate in heterocomplex formation with atypical chemokines such as macrophage migration inhibitory factor (MIF). These heterocomplexes are implicated in the regulation of inflammatory responses, leukocyte recruitment, and platelet activation, adding a new layer of complexity to the chemokine network and offering novel targets for therapeutic modulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "A D Hillian, D Londono, J M Dunn, et al. 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