Enhanced Thrombotic Responses Are Associated With Striatin Deficiency and Aldosterone

Background In addition to its role on blood pressure, aldosterone (ALDO) also affects the hemostatic system leading to increased experimental thrombosis. Striatin is an intermediate in the rapid, nongenomic actions of ALDO. Striatin heterozygote knockout (Strn+/‐) mice have salt sensitivity of blood...

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Autores principales:	Anna Gromotowicz‐Poplawska, Robert Flaumenhaft, Shadi K. Gholami, Glenn Merrill‐Skoloff, Ewa Chabielska, Gordon H. Williams, Jose R. Romero
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	aldosterone fibrin platelet striatin thrombosis Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/c7748ae1843e444a9499d422550227ff
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spelling	oai:doaj.org-article:c7748ae1843e444a9499d422550227ff2021-11-16T10:22:44ZEnhanced Thrombotic Responses Are Associated With Striatin Deficiency and Aldosterone10.1161/JAHA.121.0229752047-9980https://doaj.org/article/c7748ae1843e444a9499d422550227ff2021-11-01T00:00:00Zhttps://www.ahajournals.org/doi/10.1161/JAHA.121.022975https://doaj.org/toc/2047-9980Background In addition to its role on blood pressure, aldosterone (ALDO) also affects the hemostatic system leading to increased experimental thrombosis. Striatin is an intermediate in the rapid, nongenomic actions of ALDO. Striatin heterozygote knockout (Strn+/‐) mice have salt sensitivity of blood pressure and mildly chronically increased ALDO levels. In addition, in humans, striatin polymorphic gene variants are associated with increased salt sensitivity of blood pressure. Thus, we hypothesized that striatin deficiency would be associated with an increased prothrombotic response. Methods and Results Strn+/ ‐ mice and wild‐type littermates were maintained on a liberal sodium diet (1.6%). We measured in vivo thrombus formation following laser‐induced injury in cremaster arterioles using intravital microscopy. Mice were randomized to intravenous administration of ALDO or its vehicle. Acutely, ALDO increased thrombotic responses in wild‐type mice (P<0.01) versus controls within minutes as determined by increased platelet accumulation and fibrin deposition at the site of laser injury. We then compared thrombus formation without ALDO administration in Strn+/‐ and wild‐type mice. Strn+/‐ mice showed highly significant increases in laser‐induced thrombosis (P<0.001), as shown by increased platelet accumulation and fibrin deposition. Interestingly, the response in the Strn+/‐ mice basally was far greater than the wild‐type mice with ALDO administration, and ALDO administration produced no additional effect on thrombus responses in Strn+/‐ mice. Conclusions These results demonstrate a novel protective role of striatin in experimental thrombosis. Such a protective effect may be reduced in human striatin risk allele carriers, given the similar salt sensitivity of blood pressure in these individuals and Strn+/‐ mice.Anna Gromotowicz‐PoplawskaRobert FlaumenhaftShadi K. GholamiGlenn Merrill‐SkoloffEwa ChabielskaGordon H. WilliamsJose R. RomeroWileyarticlealdosteronefibrinplateletstriatinthrombosisDiseases of the circulatory (Cardiovascular) systemRC666-701ENJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 10, Iss 22 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	aldosterone fibrin platelet striatin thrombosis Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	aldosterone fibrin platelet striatin thrombosis Diseases of the circulatory (Cardiovascular) system RC666-701 Anna Gromotowicz‐Poplawska Robert Flaumenhaft Shadi K. Gholami Glenn Merrill‐Skoloff Ewa Chabielska Gordon H. Williams Jose R. Romero Enhanced Thrombotic Responses Are Associated With Striatin Deficiency and Aldosterone
description	Background In addition to its role on blood pressure, aldosterone (ALDO) also affects the hemostatic system leading to increased experimental thrombosis. Striatin is an intermediate in the rapid, nongenomic actions of ALDO. Striatin heterozygote knockout (Strn+/‐) mice have salt sensitivity of blood pressure and mildly chronically increased ALDO levels. In addition, in humans, striatin polymorphic gene variants are associated with increased salt sensitivity of blood pressure. Thus, we hypothesized that striatin deficiency would be associated with an increased prothrombotic response. Methods and Results Strn+/ ‐ mice and wild‐type littermates were maintained on a liberal sodium diet (1.6%). We measured in vivo thrombus formation following laser‐induced injury in cremaster arterioles using intravital microscopy. Mice were randomized to intravenous administration of ALDO or its vehicle. Acutely, ALDO increased thrombotic responses in wild‐type mice (P<0.01) versus controls within minutes as determined by increased platelet accumulation and fibrin deposition at the site of laser injury. We then compared thrombus formation without ALDO administration in Strn+/‐ and wild‐type mice. Strn+/‐ mice showed highly significant increases in laser‐induced thrombosis (P<0.001), as shown by increased platelet accumulation and fibrin deposition. Interestingly, the response in the Strn+/‐ mice basally was far greater than the wild‐type mice with ALDO administration, and ALDO administration produced no additional effect on thrombus responses in Strn+/‐ mice. Conclusions These results demonstrate a novel protective role of striatin in experimental thrombosis. Such a protective effect may be reduced in human striatin risk allele carriers, given the similar salt sensitivity of blood pressure in these individuals and Strn+/‐ mice.
format	article
author	Anna Gromotowicz‐Poplawska Robert Flaumenhaft Shadi K. Gholami Glenn Merrill‐Skoloff Ewa Chabielska Gordon H. Williams Jose R. Romero
author_facet	Anna Gromotowicz‐Poplawska Robert Flaumenhaft Shadi K. Gholami Glenn Merrill‐Skoloff Ewa Chabielska Gordon H. Williams Jose R. Romero
author_sort	Anna Gromotowicz‐Poplawska
title	Enhanced Thrombotic Responses Are Associated With Striatin Deficiency and Aldosterone
title_short	Enhanced Thrombotic Responses Are Associated With Striatin Deficiency and Aldosterone
title_full	Enhanced Thrombotic Responses Are Associated With Striatin Deficiency and Aldosterone
title_fullStr	Enhanced Thrombotic Responses Are Associated With Striatin Deficiency and Aldosterone
title_full_unstemmed	Enhanced Thrombotic Responses Are Associated With Striatin Deficiency and Aldosterone
title_sort	enhanced thrombotic responses are associated with striatin deficiency and aldosterone
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/c7748ae1843e444a9499d422550227ff
work_keys_str_mv	AT annagromotowiczpoplawska enhancedthromboticresponsesareassociatedwithstriatindeficiencyandaldosterone AT robertflaumenhaft enhancedthromboticresponsesareassociatedwithstriatindeficiencyandaldosterone AT shadikgholami enhancedthromboticresponsesareassociatedwithstriatindeficiencyandaldosterone AT glennmerrillskoloff enhancedthromboticresponsesareassociatedwithstriatindeficiencyandaldosterone AT ewachabielska enhancedthromboticresponsesareassociatedwithstriatindeficiencyandaldosterone AT gordonhwilliams enhancedthromboticresponsesareassociatedwithstriatindeficiencyandaldosterone AT joserromero enhancedthromboticresponsesareassociatedwithstriatindeficiencyandaldosterone
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Enhanced Thrombotic Responses Are Associated With Striatin Deficiency and Aldosterone

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