bigEndothelin-1

bigEndothelin-1
May 15, 2021 7:25pm

Here is a significant study of a plasma component associated with thrombosis in immune thrombotic thrombocytopenic purpura published by a colleague and friend, Dr. X Long Zheng, an iTTP expert, and his associate, Dr. Nancy Lu: Lu R, Zheng XL. Plasma levels of bigEndothelin-1 are associated with renal insufficiency and in-hospital mortality of immune thrombotic thrombocytopenic purpura. Thromb Haemost. 2021 May 13. doi: 10.1055/a-1508-8347. Online ahead of print.
 

Immune thrombotic thrombocytopenic purpura (iTTP) is caused by severe deficiency of plasma ADAMTS13 activity. Despite advances in early diagnosis and management, the mortality rate of acute iTTP remains high in a large part of the world where access to some of the most novel therapies is limited. To determine the role of plasma bigEndothelin-1 (bigET-1) or its bioactive product ET-1 as a biomarker and/or a pathogenic factor in acute iTTP, plasma levels of bigET-1 were determined using an immunoassay in patients with iTTP on admission and during remission, as well as in healthy controls; moreover, the biological effect of ET-1 in thrombus formation was determined by a microfluidic assay. We show that plasma levels of bigET-1 were dramatically increased in patients with acute iTTP on admission, which was significantly decreased during clinical response/remission; elevated admission levels of plasma bigET-1 were associated with low estimated glomerular filtration rate, the need for intensive care unit admission or intubation, and in-hospital mortality. Moreover, an addition of a bioactive product ET-1 to cultured endothelial cells in a microfluidic channel dramatically accelerated the rate of thrombus formation under arterial flow. Our results demonstrate for the first time a potential role of measuring plasma bigET-1 in patients with acute iTTP in assessing the disease severity and risk of in-hospital mortality, which may help stratify patients for a more aggressive monitoring and therapeutic strategy; also, the bioactive ET-1, derived from bigET-1, may result in acute renal injury in TTP patient, likely through its vasoconstriction and prothrombotic properties.

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Here is a significant study of a plasma component associated with thrombosis in immune thrombotic thrombocytopenic purpura published by a colleague and friend, Dr. X Long Zheng, an iTTP expert, and his associate, Dr. Nancy Lu: Lu R, Zheng XL. Plasma levels of bigEndothelin-1 are associated with renal insufficiency and in-hospital mortality of immune thrombotic thrombocytopenic purpura. Thromb Haemost. 2021 May 13. doi: 10.1055/a-1508-8347. Online ahead of print.
 

Immune thrombotic thrombocytopenic purpura (iTTP) is caused by severe deficiency of plasma ADAMTS13 activity. Despite advances in early diagnosis and management, the mortality rate of acute iTTP remains high in a large part of the world where access to some of the most novel therapies is limited. To determine the role of plasma bigEndothelin-1 (bigET-1) or its bioactive product ET-1 as a biomarker and/or a pathogenic factor in acute iTTP, plasma levels of bigET-1 were determined using an immunoassay in patients with iTTP on admission and during remission, as well as in healthy controls; moreover, the biological effect of ET-1 in thrombus formation was determined by a microfluidic assay. We show that plasma levels of bigET-1 were dramatically increased in patients with acute iTTP on admission, which was significantly decreased during clinical response/remission; elevated admission levels of plasma bigET-1 were associated with low estimated glomerular filtration rate, the need for intensive care unit admission or intubation, and in-hospital mortality. Moreover, an addition of a bioactive product ET-1 to cultured endothelial cells in a microfluidic channel dramatically accelerated the rate of thrombus formation under arterial flow. Our results demonstrate for the first time a potential role of measuring plasma bigET-1 in patients with acute iTTP in assessing the disease severity and risk of in-hospital mortality, which may help stratify patients for a more aggressive monitoring and therapeutic strategy; also, the bioactive ET-1, derived from bigET-1, may result in acute renal injury in TTP patient, likely through its vasoconstriction and prothrombotic properties.

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