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Article ; Online: Role of Nitric Oxide in Megakaryocyte Function.

Asgari, Amir / Jurasz, Paul

International journal of molecular sciences

2023 Volume 24, Issue 9

Abstract: Megakaryocytes are the main members of the hematopoietic system responsible for regulating vascular homeostasis through their progeny platelets, which are generally known for maintaining hemostasis. Megakaryocytes are characterized as large polyploid ... ...

Abstract	Megakaryocytes are the main members of the hematopoietic system responsible for regulating vascular homeostasis through their progeny platelets, which are generally known for maintaining hemostasis. Megakaryocytes are characterized as large polyploid cells that reside in the bone marrow but may also circulate in the vasculature. They are generated directly or through a multi-lineage commitment step from the most primitive progenitor or Hematopoietic Stem Cells (HSCs) in a process called "megakaryopoiesis". Immature megakaryocytes enter a complicated development process defined as "thrombopoiesis" that ultimately results in the release of extended protrusions called proplatelets into bone marrow sinusoidal or lung microvessels. One of the main mediators that play an important modulatory role in hematopoiesis and hemostasis is nitric oxide (NO), a free radical gas produced by three isoforms of nitric oxide synthase within the mammalian cells. In this review, we summarize the effect of NO and its signaling on megakaryopoiesis and thrombopoiesis under both physiological and pathophysiological conditions.
MeSH term(s)	Animals ; Megakaryocytes/physiology ; Nitric Oxide ; Blood Platelets ; Thrombopoiesis ; Hematopoietic Stem Cells/physiology ; Mammals
Chemical Substances	Nitric Oxide (31C4KY9ESH)
Language	English
Publishing date	2023-05-02
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24098145
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Article: Editorial: Established and Novel Roles of Platelets in Health and Disease.

Jurasz, Paul / Ignjatovic, Vera / Lordkipanidzé, Marie

Frontiers in cardiovascular medicine

2022 Volume 9, Page(s) 835615

Language	English
Publishing date	2022-01-31
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2022.835615
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Article: Advances in Platelet Subpopulation Research.

Lesyk, Gabriela / Jurasz, Paul

Frontiers in cardiovascular medicine

2019 Volume 6, Page(s) 138

Abstract: Although lacking a nucleus, platelets are increasingly recognized not only for their complexity, but also for their diversity. Some 50 years ago platelet subpopulations were characterized by size and density, and these characteristics were thought to ... ...

Abstract	Although lacking a nucleus, platelets are increasingly recognized not only for their complexity, but also for their diversity. Some 50 years ago platelet subpopulations were characterized by size and density, and these characteristics were thought to reflect platelet aging. Since, our knowledge of platelet heterogeneity has grown to recognize that differences in platelet biochemistry and function exist. This includes the identification of vanguard and follower platelets, platelets with differing procoagulant ability including "COAT-platelets" which enhance procoagulant protein retention on their surface, and most recently, the identification of platelet subpopulations with a differential ability to generate and respond to nitric oxide. Hence, in this mini-review, we summarize the current knowledge of platelet subpopulation diversity focusing on their physical, biochemical, and functional heterogeneity. In addition, we review how platelet subpopulations may change between health and disease and how differences among platelets may influence response to anti-platelet therapy. Finally, we look forward and discuss some of the future directions and challenges for this growing field of platelet research.
Language	English
Publishing date	2019-09-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2019.00138
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Article ; Online: L-Arginine and NOS activity, a complex relationship.

Le Melledo, Jean-Michel / Baker, Glen / Gyenes, Gabor / Tsuyuki, Ross / Jurasz, Paul

Psychopharmacology

2021 Volume 238, Issue 4, Page(s) 1223–1224

MeSH term(s)	Arginine ; Nitric Oxide Synthase
Chemical Substances	Arginine (94ZLA3W45F) ; Nitric Oxide Synthase (EC 1.14.13.39)
Language	English
Publishing date	2021-02-17
Publishing country	Germany
Document type	Letter ; Comment
ZDB-ID	130601-7
ISSN	1432-2072 ; 0033-3158
ISSN (online)	1432-2072
ISSN	0033-3158
DOI	10.1007/s00213-021-05799-7
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Article ; Online: The role of the androgen receptor in prostate cancer-induced platelet aggregation and platelet-induced invasion.

Rudzinski, Jan K / Govindasamy, Natasha P / Lewis, John D / Jurasz, Paul

Journal of thrombosis and haemostasis : JTH

2020 Volume 18, Issue 11, Page(s) 2976–2986

Abstract: Background: Metastatic prostate cancer progresses from a hormone sensitive androgen receptor expressing phenotype to a hormone insensitive androgen receptor-independent subtype with low overall survival. Human platelets contribute to metastasis via ... ...

Abstract	Background: Metastatic prostate cancer progresses from a hormone sensitive androgen receptor expressing phenotype to a hormone insensitive androgen receptor-independent subtype with low overall survival. Human platelets contribute to metastasis via tumor cell-induced platelet aggregation, which in part enhances cancer cell invasion. Given the more aggressive nature of hormone insensitive prostate cancer, we hypothesized that androgen receptor-negative prostate cancer cells exhibit higher platelet aggregation potency and invasive response compared to cells with androgen receptor. Objective: To characterize the role of androgen receptors in prostate cancer-induced platelet aggregation and platelet-induced invasion. Methods: Tumor cell-induced platelet aggregation experiments were performed with platelets from healthy human donors and benign prostate (RWPE-1) and prostate cancer cell lines positive (LNCaP) and negative for androgen receptor (DU145 and PC3). Immunoblot measured prostate cancer prothrombin. Modified Boyden chamber invasion assays and zymography were performed to assess the effects of platelets on prostate cancer cell invasion and matrix metalloproteinase (MMP) expression, respectively. Results: Androgen receptor-positive prostate cancer cell lines failed to induce platelet aggregation. However, androgen receptor-inhibited and -negative cell lines all induced platelet aggregation, which was abolished by dabigatran. Androgen receptor-inhibited and -negative cell lines demonstrated greater expression of prothrombin than androgen receptor-positive cells. Platelets enhanced invasion and MMP-2 and -9 expression by androgen receptor-inhibited and negative prostate cancer cells, but not that of the androgen receptor-positive cells. Conclusions: Androgen receptor loss within prostate cancer results in increased thrombogenicity due to upregulation of prothrombin expression. Reciprocally, platelets enhance invasion of androgen receptor-negative prostate cancer cells via increased MMP expression.
MeSH term(s)	Blood Platelets ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Male ; Platelet Aggregation ; Prostatic Neoplasms ; Receptors, Androgen
Chemical Substances	AR protein, human ; Receptors, Androgen
Language	English
Publishing date	2020-08-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2112661-6
ISSN	1538-7836 ; 1538-7933
ISSN (online)	1538-7836
ISSN	1538-7933
DOI	10.1111/jth.15020
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Zs.A 5805: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: The role of platelets in the tumor microenvironment: From solid tumors to leukemia.

Yan, MengJie / Jurasz, Paul

Biochimica et biophysica acta

2016 Volume 1863, Issue 3, Page(s) 392–400

Abstract: Platelets are increasingly being recognized for promoting tumor growth and metastasis. Many cells derived from solid tumors have the ability to aggregate platelets, and this ability correlates with their metastatic potential. Over the past half century, ... ...

Abstract	Platelets are increasingly being recognized for promoting tumor growth and metastasis. Many cells derived from solid tumors have the ability to aggregate platelets, and this ability correlates with their metastatic potential. Over the past half century, our understanding of tumor cell-induced platelet aggregation (TCIPA) has grown beyond the simple concept that tumor cell-containing microthrombi mechanically embolize the microvasculature. Tumor cell-activated platelets secrete a multitude of factors that reciprocally act on tumor cells, as well as other cells within the tumor microenvironment; thus, affecting both parenychma and tumor-associated stroma. In this review, we summarize the current knowledge of tumor cell-platelet interactions and their influence on the tumor microenvironment, including how these interactions impact neoplastic epithelial cells, endothelial cells, pericytes, fibroblasts, immune cells, and early metastatic niches. In addition, we review the current knowledge of platelet-cancer cell interactions within hematological malignancies and speculate on how platelets may influence the leukemic microenvironment. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza.
MeSH term(s)	Blood Platelets/pathology ; Cell Communication ; Endothelial Cells/pathology ; Humans ; Leukemia/pathology ; Models, Biological ; Neoplasm Metastasis ; Neoplasms/blood supply ; Neoplasms/pathology ; Platelet Aggregation ; Tumor Microenvironment
Language	English
Publishing date	2016-03
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbamcr.2015.07.008
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Article ; Online: Preferential interaction of platelets with prostate cancer cells with stem cell markers.

Rudzinski, Jan K / Govindasamy, Natasha P / Asgari, Amir / Saito, Max S / Lewis, John D / Jurasz, Paul

Thrombosis research

2021 Volume 206, Page(s) 42–51

Abstract: Background: Prostate cancer (PCa) may be initiated by CD133+/CD44+ expressing stem cell-like cells (PCSC), which are also thought to drive metastasis. Platelets also contribute to metastasis via tumor cell-induced platelet aggregation (TCIPA), which in ... ...

Abstract	Background: Prostate cancer (PCa) may be initiated by CD133+/CD44+ expressing stem cell-like cells (PCSC), which are also thought to drive metastasis. Platelets also contribute to metastasis via tumor cell-induced platelet aggregation (TCIPA), which in part enhances cancer cell invasion. Moreover, activated platelets secrete stromal derived growth factor-1α (SDF-1α) that can mobilize CSCs via the CXCR4 receptor. However, the potential reciprocal interactions between CSCs and platelets have not been investigated. Objective: To characterize the mechanisms behind PCSC-platelet interaction. Methods: Fluorescence Activated Cell Sorting was utilized to separate DU145 and PC3 PCa cells into CD133+/CD44+, CD133+/CD44-, CD44+/CD133-, and CD133-/CD44- subpopulations and to measure their CXCR4 surface expression. PCa subpopulation TCIPA experiments were performed using aggregometry and immunoblot was used to measure prothrombin. Platelet SDF-1α secretion was measured by ELISA. Modified-Boyden chamber assays were used to assess the role of SDF-1α:CXCR4 pathway in platelet-PCSC interactions. Results: DU145 and PC3 expressing both CD133 and CD44 stem cell markers accounted for only small fractions of total cells (DU145: CD133+/CD44+ 3.44 ± 1.45% vs. CD133+/CD44- 1.56 ± 0.45% vs. CD44+/CD133- 68.19 ± 6.25% vs. CD133-/CD44- 20.36 ± 4.51%). However, CD133+ subpopulations induced the greatest amount of aggregation compared to CD44+/CD133- and double-negative DU145, and this aggregation potency of CD133+ PCa cells corresponded with high levels of prothrombin expression. Additionally, CD133+ subpopulations expressed significantly higher level of CXCR4 compared to CD133-/CD44- and CD44+/CD133-. Disruption of SDF-1α:CXCR4 pathway reduced platelet-induced PCSC invasion. Conclusions: CD133+/CD44+ and CD133+/CD44- PCSCs have highest platelet aggregation potency, which could be attributed to their increased prothrombin expression. Reciprocally, platelet-derived SDF-1α stimulates PCSC invasion.
MeSH term(s)	Blood Platelets ; Cell Line, Tumor ; Chemokine CXCL12 ; Humans ; Male ; Neoplastic Stem Cells ; Prostatic Neoplasms ; Receptors, CXCR4
Chemical Substances	Chemokine CXCL12 ; Receptors, CXCR4
Language	English
Publishing date	2021-08-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	121852-9
ISSN	1879-2472 ; 0049-3848
ISSN (online)	1879-2472
ISSN	0049-3848
DOI	10.1016/j.thromres.2021.08.008
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Article ; Online: Inhibition of platelet aggregation by activation of platelet intermediate conductance Ca

Back, Valentina / Asgari, Amir / Franczak, Aleksandra / Saito, Max / Castaneda Zaragoza, Diego / Sandow, Shaun L / Plane, Frances / Jurasz, Paul

Journal of thrombosis and haemostasis : JTH

2022 Volume 20, Issue 11, Page(s) 2587–2600

Abstract: Background: Within the vasculature platelets and endothelial cells play crucial roles in hemostasis and thrombosis. Platelets, like endothelial cells, possess intermediate conductance Ca: Objectives: We investigated whether IK: Methods: Platelets ... ...

Abstract	Background: Within the vasculature platelets and endothelial cells play crucial roles in hemostasis and thrombosis. Platelets, like endothelial cells, possess intermediate conductance Ca Objectives: We investigated whether IK Methods: Platelets were isolated from human volunteers. Aggregometry, confocal microscopy, and a novel flow chamber model, the Quartz Crystal Microbalance (QCM) were used to assess platelet function. Flow cytometry was used to measure platelet NO production, calcium signaling, membrane potential, integrin α Results: Platelet IK Conclusions: Platelet IK
MeSH term(s)	Humans ; Intermediate-Conductance Calcium-Activated Potassium Channels/pharmacology ; Endothelial Cells/metabolism ; Nitric Oxide/metabolism ; Potassium Channels/pharmacology ; Platelet Aggregation ; Calcium/metabolism ; Phosphatidylserines ; Platelet Aggregation Inhibitors/pharmacology ; Integrins
Chemical Substances	Intermediate-Conductance Calcium-Activated Potassium Channels ; Nitric Oxide (31C4KY9ESH) ; Potassium Channels ; Calcium (SY7Q814VUP) ; Phosphatidylserines ; Platelet Aggregation Inhibitors ; Integrins
Language	English
Publishing date	2022-08-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2112661-6
ISSN	1538-7836 ; 1538-7933
ISSN (online)	1538-7836
ISSN	1538-7933
DOI	10.1111/jth.15827
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Article: Incorporation of β-actin loading control into zymography.

Govindasamy, Natasha / Yan, MengJie / Jurasz, Paul

Journal of biological methods

2017 Volume 3, Issue 4

Abstract: Gelatin zymography and immunoblot are widely used gel electrophoresis techniques to study matrix metalloproteinases-2 and -9. Each method has its advantages and disadvantages. Zymography is exquisitely sensitive but offers no loading control to ensure ... ...

Abstract	Gelatin zymography and immunoblot are widely used gel electrophoresis techniques to study matrix metalloproteinases-2 and -9. Each method has its advantages and disadvantages. Zymography is exquisitely sensitive but offers no loading control to ensure equal sample loading. Immunoblot is a 100-1000-fold less sensitive, but allows for the probing of a sample loading control such as β-actin to ensure accurate protein loading. In this report, we describe two simple protocols that combine gelatin zymography to study MMP-2 and -9 levels with an in-gel β-actin immunoblot loading control, thus combining sensitivity and accuracy in a single assay. The protocols incorporate the loading of molecular weight markers to demarcate MMP-2/-9 from the β-actin. The first protocol utilizes the overlay of a 10% zymography gel over a 5% Tris-Glycine separating gel from which the β-actin is transferred. The second protocol involves the direct transfer of the β-actin from a single 10% zymography gel.
Language	English
Publishing date	2017-02-07
Publishing country	United States
Document type	Journal Article
ISSN	2326-9901
ISSN	2326-9901
DOI	10.14440/jbm.2016.157
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Article ; Online: Potential Antimigraine Effects of Warfarin: An Exploration of Biological Mechanism with Survey of Patients.

Nilsson, Benjamin / Back, Valentina / Wei, Ran / Plane, Frances / Jurasz, Paul / Bungard, Tammy J

TH open : companion journal to thrombosis and haemostasis

2019 Volume 3, Issue 2, Page(s) e180–e189

Abstract: Case reports suggest a link between anticoagulant use and improved migraine symptoms, and a role for platelet-induced cerebral vasoconstriction in migraine pathobiology. Hence, we investigated the mechanism by which warfarin may affect migraine symptoms ... ...

Abstract	Case reports suggest a link between anticoagulant use and improved migraine symptoms, and a role for platelet-induced cerebral vasoconstriction in migraine pathobiology. Hence, we investigated the mechanism by which warfarin may affect migraine symptoms and whether there is a change in migraine symptomology in patients initiating oral anticoagulants, most commonly warfarin. The effects of warfarin on human platelet aggregation and secretion as well as platelet-induced rat cerebral artery vasoconstriction were studied. A survey of migraine and symptom change after starting or stopping oral anticoagulants was also conducted. Warfarin inhibited platelet aggregation and 5-hydroxytryptamine (5-HT) secretion in a concentration-dependent manner. Warfarin-inhibited platelet secretion products constricted middle cerebral arteries from male but not from female rats. For the survey, patient demographic information, migraine and medical history, and Migraine Disability Assessment Score (MIDAS) changes were collected. Out of 175 consenting, 40 respondents met the criteria for migraine and completed the survey. A total of 11 patients reported migraine symptom change, all coinciding with starting warfarin. Of those having symptom and MIDAS improvement, most were female with migraines with aura, whereas those worsening were male with fewer having migraine with aura. Of those reporting migraine symptom change with warfarin, female sex may be associated with improved MIDAS, and those experiencing an aura component are more likely to report a symptom change. Warfarin-mediated symptom improvement in females may occur due to inhibition of platelet 5-HT secretion and a lower sensitivity of female cerebral blood vessels to platelet-derived 5-HT-induced vasoconstriction.
Language	English
Publishing date	2019-06-21
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2901738-5
ISSN	2512-9465 ; 2567-3459
ISSN (online)	2512-9465
ISSN	2567-3459
DOI	10.1055/s-0039-1692989
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