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Accessing Altered Metabolic Profile in Acute Deep Vein Thrombosis Through Nuclear Magnetic Resonance Spectroscopy

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Autor(es):
Queiroz da Silva, Leticia ; Santana da Costa, Thyerre ; Gelain Martins, Lucas ; de Lima Montalvao, Silmara Aparecida ; Cares Huber, Stephany ; Martins Silva Soares, Sandra ; Tasic, Ljubica ; Annichino-Bizzacchi, Joyce Maria
Número total de Autores: 8
Tipo de documento: Artigo Científico
Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 26, n. 23, p. 18-pg., 2025-11-24.
Resumo

Deep venous thrombosis (DVT) is characterized by the formation of a thrombus within deep veins. The unmet need to identify new biomarkers and causal risk factors in DVT patients has led to the use of novel techniques, such as metabolite analyses. This study aimed to characterize metabolic alterations in acute DVT patients using 1H-NMR spectroscopy and determine the persistence of these changes over a six-month follow-up. Metabolomics, particularly 1H-NMR spectroscopy, was performed on serum samples from acute DVT patients (first 30 days from diagnosis) and healthy controls (HC). Additionally, 10 plasma markers were evaluated using a Luminex kit. A total of 30 patients, with a mean age of 44 +/- 12.5 years, primarily women (9 males:21 females), were included. Acute DVT patients showed elevated inflammatory markers, such as IL-6, IL-8, PDGF-AB/BB, and P-selectin, which later decreased in the follow-up group. However, adhesion molecules like sVCAM-1 and sICAM-1 have increased after six months. Metabolomics analysis revealed significantly decreased levels of glutamine, glucose, and branched-chain amino acids (BCAAs), alongside increased lactate levels in acute DVT samples. Metabolomic profiles showed only partial normalization at follow-up, indicating persistent metabolic dysregulation. Overall, the reduced glucose metabolism and increased lactate levels indicate anaerobic metabolism, likely caused by tissue hypoxia due to impaired blood flow. Glutamine, essential for DNA, ATP, and protein synthesis, was notably reduced, potentially impairing endothelial cell proliferation and vascular repair. The presence of adhesion molecules in the follow-up group confirms persistent endothelial dysfunction. These findings suggest that metabolic and endothelial alterations may persist long after acute inflammation resolves in DVT patients. In conclusion, the persistence of metabolic dysregulation suggests chronic metabolic stress in these patients, potentially resulting from ongoing endothelial damage, low-grade inflammation, or altered mitochondrial function due to past tissue hypoxia. (AU)

Processo FAPESP: 18/15618-3 - Avaliação da atividade de Células Endoteliais Formadoras de Colônia (CEFCs) circulantes em pacientes com Trombose Venosa espontânea e provocada
Beneficiário:Letícia Queiroz da Silva Justo
Modalidade de apoio: Bolsas no Brasil - Doutorado
Processo FAPESP: 16/14172-6 - Investigação de aspectos fisiopatológicos e novas abordagens terapêuticas em doenças tromboembólicas
Beneficiário:Joyce Maria Annichino-Bizzacchi
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 20/08615-8 - Exosítios de proteínas, sítios crípticos e moonlighting: identificação, mapeamento funcional e efeitos de alteração estrutural
Beneficiário:Raghuvir Krishnaswamy Arni
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 23/02338-0 - Anotação e identificação de metabólitos em células selvagens e modificadas usando abordagem de RMN não direcionada e integrada
Beneficiário:Thyerre Santana da Costa
Modalidade de apoio: Bolsas no Brasil - Doutorado Direto