Dataset Information

Plasma tissue-type plasminogen activator is associated with lipoprotein(a) and clinical outcomes in hospitalized patients with COVID-19.

ABSTRACT:

Background

Patients with COVID-19 have a higher risk of thrombosis and thromboembolism, but the underlying mechanism(s) remain to be fully elucidated. In patients with COVID-19, high lipoprotein(a) (Lp(a)) is positively associated with the risk of ischemic heart disease. Lp(a), composed of an apoB-containing particle and apolipoprotein(a) (apo(a)), inhibits the key fibrinolytic enzyme, tissue-type plasminogen activator (tPA). However, whether the higher Lp(a) associates with lower tPA activity, the longitudinal changes of these parameters in hospitalized patients with COVID-19, and their correlation with clinical outcomes are unknown.

Objectives

To assess if Lp(a) associates with lower tPA activity in COVID-19 patients, and how in COVID-19 populations Lp(a) and tPA change post infection.

Methods

Endogenous tPA enzymatic activity, tPA or Lp(a) concentration were measured in plasma from hospitalized patients with and without COVID-19. The association between plasma tPA and adverse clinical outcomes was assessed.

Results

In hospitalized patients with COVID-19, we found lower tPA enzymatic activity and higher plasma Lp(a) than that in non-COVID-19 controls. During hospitalization, Lp(a) increased and tPA activity decreased, which associates with mortality. Among those who survived, Lp(a) decreased and tPA enzymatic activity increased during recovery. In patients with COVID-19, tPA activity is inversely correlated with tPA concentrations, thus, in another larger COVID-19 cohort, we utilized plasma tPA concentration as a surrogate to inversely reflect tPA activity. The tPA concentration was positively associated with death, disease severity, plasma inflammatory, and prothrombotic markers, and with length of hospitalization among those who were discharged.

Conclusion

High Lp(a) concentration provides a possible explanation for low endogenous tPA enzymatic activity, and poor clinical outcomes in patients with COVID-19.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC10480648 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Plasma tissue-type plasminogen activator is associated with lipoprotein(a) and clinical outcomes in hospitalized patients with COVID-19.

Zhang Ziyu Z Dai Wen W Zhu Wen W Rodriguez Maya M Lund Hayley H Xia Yuhe Y Chen Yiliang Y Rau Mary M Schneider Ellen Anje EA Graham Mary Beth MB Jobe Shawn S Wang Demin D Cui Weiguo W Wen Renren R Whiteheart Sidney W SW Wood Jeremy P JP Silverstein Roy R Berger Jeffery S JS Kreuziger Lisa Baumann LB Barrett Tessa J TJ Zheng Ze Z

Research and practice in thrombosis and haemostasis 20230808 6

<h4>Background</h4>Patients with COVID-19 have a higher risk of thrombosis and thromboembolism, but the underlying mechanism(s) remain to be fully elucidated. In patients with COVID-19, high lipoprotein(a) (Lp(a)) is positively associated with the risk of ischemic heart disease. Lp(a), composed of an apoB-containing particle and apolipoprotein(a) (apo(a)), inhibits the key fibrinolytic enzyme, tissue-type plasminogen activator (tPA). However, whether the higher Lp(a) associates with lower tPA ac ...[more]

PMID: 37680312

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Project description:The lack of available biomarkers for diagnosing and predicting different stages of coronavirus disease 2019 (COVID-19) is currently one of the main challenges that clinicians are facing. Recent evidence indicates that the plasma levels of specific miRNAs may be significantly modified in COVID-19 patients. Large-scale deep sequencing analysis of small RNA expression was performed on plasma samples from 40 patients hospitalized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (between March and May 2020) (median 13.50 [IQR 9–24] days since symptoms initiation) and 21 healthy noninfected individuals. Patients were categorized as hospitalized not requiring oxygen therapy (n = 6), hospitalized requiring low-flow oxygen (n = 23), and hospitalized requiring high-flow oxygen support (n = 11). A total of 1218 different micro(mi)RNAs were identified. When compared with healthy noninfected donors, SARS-CoV-2 infected patients showed significantly (fold change [FC] >1.2 and adjusted p [padj] <0.05) altered expression of 190 miRNAs. The top 10 differentially expressed (DE) miRNAs were miR-122-5p, let-7b-5p, miR-146a-5p, miR-342-3p, miR-146b-5p, miR-629-5p, miR-24-3p, miR-12136, let-7a-5p, and miR-191-5p, which displayed FC and padj values ranging from 153 to 5 and 2.51 × 10-32 to 2.21 × 10-21, respectively, which unequivocally diagnosed SARS-CoV-2 infection. No differences in blood cell counts and biochemical plasma parameters, including interleukin 6, ferritin and D-dimer, were observed between COVID-19 patients on high-flow oxygen therapy, low-flow oxygen therapy, or not requiring oxygen therapy. Notably, 31 significantly deregulated miRNAs were found when patients on high- and low-flow oxygen therapy were compared. Similarly, 6 DE miRNAs were identified between patients on high flow and those not requiring oxygen therapy. SARS-CoV-2 infection generates a specific miRNA signature in hospitalized patients. Furthermore, specific miRNA profiles are associated with COVID-19 prognosis in severe patients.

Dataset Information

Plasma tissue-type plasminogen activator is associated with lipoprotein(a) and clinical outcomes in hospitalized patients with COVID-19.

Background

Objectives

Methods

Results

Conclusion

Publications

Plasma tissue-type plasminogen activator is associated with lipoprotein(a) and clinical outcomes in hospitalized patients with COVID-19.

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