Procoagulant phenotype induced by oxidized high-density lipoprotein associates with acute kidney injury and death

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dc.contributor.authorPrado, Yolanda
dc.contributor.authorPerez, Lorena
dc.contributor.authorEltit, Felipe
dc.contributor.authorEcheverria, Cesar
dc.contributor.authorLlancalahuen, Felipe M.
dc.contributor.authorTapia, Pablo
dc.contributor.authorGonzalez, Pablo A.
dc.contributor.authorKalergis, Alexis M.
dc.contributor.authorCabello-Verrugio, Claudio
dc.contributor.authorSimon, Felipe
dc.date.accessioned2025-01-20T20:18:22Z
dc.date.available2025-01-20T20:18:22Z
dc.date.issued2023
dc.description.abstractBackground: Oxidative stress derived from severe systemic inflammation promotes conversion from high-density lipoprotein HDL to oxidized HDL (oxHDL), which interacts with vascular endothelial cells (ECs). OxHDL acquires procoagulant features playing a role in modulating coagulation, which has been linked with organ failure in ICU patients. However, whether oxHDL elicits a ECs-mediated procoagulant phenotype generating organ failure and death, and the underlying molecular mechanism is not known. Therefore, we studied whether oxHDL-treated rats and high-oxHDL ICU patients exhibit a procoagulant phenotype and its association with kidney injury and mortality and the endothelial underlying molecular mechanism. Methods: Human ECs, oxHDL-treated rats and ICU patients were subjected to several cellular and molecular studies, coagulation analyses, kidney injury assessment and mortality determination. Results: OxHDL-treated ECs showed a procoagulant protein expression reprograming characterized by increased E-/P-selectin and vWF mRNA expression through specific signaling pathways. OxHDL-treated rats exhibited a procoagulant phenotype and modified E-/P-selectin, vWF, TF and t-PA mRNA expression correlating with plasma TF, t-PA and D-dimer. Also, showed increased death events and the relative risk of death, and increased creat-inine, urea, BUN/creatinine ratio, KIM-1, NGAL, beta 2M, and decreased eGFR, all concordant with kidney injury, correlated with plasma TF, t-PA and D-dimer. ICU patients showed correlation between plasma oxHDL and increased creatinine, cystatin, BUN, BUN/creatinine ratio, KIM-1, NGAL, beta 2M, and decreased GFR. Notably, ICU high-oxHDL patients showed decreased survival. Interestingly, altered coagulation factors TF, t-PA and D-dimer correlated with both increased oxHDL levels and kidney injury markers, indicating a connection between these factors. Conclusion: Increased circulating oxHDL generates an endothelial-dependent procoagulant phenotype that as-sociates with acute kidney injury and increased risk of death.
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.thromres.2023.01.014
dc.identifier.eissn1879-2472
dc.identifier.issn0049-3848
dc.identifier.urihttps://doi.org/10.1016/j.thromres.2023.01.014
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/92457
dc.identifier.wosidWOS:000925692100001
dc.language.isoen
dc.pagina.final23
dc.pagina.inicio7
dc.revistaThrombosis research
dc.rightsacceso restringido
dc.subjectOxidized lipoprotein
dc.subjectKidney injury
dc.subjectCoagulation
dc.subjectBiomarker
dc.subjectRisk of death
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleProcoagulant phenotype induced by oxidized high-density lipoprotein associates with acute kidney injury and death
dc.typeartículo
dc.volumen223
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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