Impact of angiotensin-converting enzyme inhibition on platelet tissue factor expression in stroke-prone rats

Research output: Contribution to journalArticle

Abstract

Objective: Hypertension is a well known risk factor for thrombotic events such as myocardial infarction and stroke. Platelets express tissue factor (TF), the key activator of blood coagulation and thrombus formation. The number of TF-positive platelets increases in pathological conditions characterized by thrombotic complications but whether this occurs in hypertension is unknown. Here we investigated whether platelet TF expression is increased in a hypertensive status through a mechanism acting on megakaryocytes; the phenomenon could be modulated by antihypertensive drug as captopril; angiotensin (AngII) influences platelet TF expression. Methods: Spontaneously hypertensive stroke prone (SHRSP) rats received standard diet (StD) or a Japanese high-salt permissive diet (JpD). After 3 weeks, JpD animals were randomized to receive captopril or vehicle. Normotensive Wistar Kyoto (WKY) rats were used as controls. Cell-associated TF expression and activity were analyzed by flow cytometry and calibrated automated thrombogram, respectively. Results: Hypertensive StD-SHRSP showed an increased number of TF-positive platelets compared with normotensive WKY. After JpD administration, SHRSP developed severe hypertension and renal damage; the number of TF-positive megakaryocytes significantly increased compared with StD-SHRSP resulting in a higher number of TF-positive platelets with a faster kinetic of thrombin generation. These effects were reverted by captopril. Ex-vivo stimulation of platelets, isolated from normotensive WKY and from healthy individuals, with AngII induced a concentration-dependent increase of surface-associated TF expression. Conclusion: The current study shows for the first time that in hypertension the number of TF-positive megakaryocytes increases thus releasing in the circulation more platelets carrying a functionally active TF. AngII stimulates platelets to express TF.

Original languageEnglish
Pages (from-to)1360-1371
Number of pages12
JournalJournal of Hypertension
Volume36
Issue number6
DOIs
Publication statusPublished - Jun 1 2018

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Thromboplastin
Peptidyl-Dipeptidase A
Blood Platelets
Stroke
Megakaryocytes
Captopril
Angiotensins
Diet
Hypertension
Renal Hypertension
Inbred WKY Rats
Blood Coagulation
Thrombin
Antihypertensive Agents
Flow Cytometry
Thrombosis
Salts
Myocardial Infarction

Keywords

  • angiotensin II
  • antihypertensive drug
  • blood pressure
  • platelets
  • stroke-prone rats
  • tissue factor

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

@article{14be8afa3afa44f1bc14c3f6967fd73c,
title = "Impact of angiotensin-converting enzyme inhibition on platelet tissue factor expression in stroke-prone rats",
abstract = "Objective: Hypertension is a well known risk factor for thrombotic events such as myocardial infarction and stroke. Platelets express tissue factor (TF), the key activator of blood coagulation and thrombus formation. The number of TF-positive platelets increases in pathological conditions characterized by thrombotic complications but whether this occurs in hypertension is unknown. Here we investigated whether platelet TF expression is increased in a hypertensive status through a mechanism acting on megakaryocytes; the phenomenon could be modulated by antihypertensive drug as captopril; angiotensin (AngII) influences platelet TF expression. Methods: Spontaneously hypertensive stroke prone (SHRSP) rats received standard diet (StD) or a Japanese high-salt permissive diet (JpD). After 3 weeks, JpD animals were randomized to receive captopril or vehicle. Normotensive Wistar Kyoto (WKY) rats were used as controls. Cell-associated TF expression and activity were analyzed by flow cytometry and calibrated automated thrombogram, respectively. Results: Hypertensive StD-SHRSP showed an increased number of TF-positive platelets compared with normotensive WKY. After JpD administration, SHRSP developed severe hypertension and renal damage; the number of TF-positive megakaryocytes significantly increased compared with StD-SHRSP resulting in a higher number of TF-positive platelets with a faster kinetic of thrombin generation. These effects were reverted by captopril. Ex-vivo stimulation of platelets, isolated from normotensive WKY and from healthy individuals, with AngII induced a concentration-dependent increase of surface-associated TF expression. Conclusion: The current study shows for the first time that in hypertension the number of TF-positive megakaryocytes increases thus releasing in the circulation more platelets carrying a functionally active TF. AngII stimulates platelets to express TF.",
keywords = "angiotensin II, antihypertensive drug, blood pressure, platelets, stroke-prone rats, tissue factor",
author = "Marta Brambilla and Paolo Gelosa and Laura Rossetti and Laura Castiglioni and Chiara Zara and Paola Canzano and Elena Tremoli and Luigi Sironi and Marina Camera",
year = "2018",
month = "6",
day = "1",
doi = "10.1097/HJH.0000000000001702",
language = "English",
volume = "36",
pages = "1360--1371",
journal = "Journal of Hypertension",
issn = "0263-6352",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Impact of angiotensin-converting enzyme inhibition on platelet tissue factor expression in stroke-prone rats

AU - Brambilla, Marta

AU - Gelosa, Paolo

AU - Rossetti, Laura

AU - Castiglioni, Laura

AU - Zara, Chiara

AU - Canzano, Paola

AU - Tremoli, Elena

AU - Sironi, Luigi

AU - Camera, Marina

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Objective: Hypertension is a well known risk factor for thrombotic events such as myocardial infarction and stroke. Platelets express tissue factor (TF), the key activator of blood coagulation and thrombus formation. The number of TF-positive platelets increases in pathological conditions characterized by thrombotic complications but whether this occurs in hypertension is unknown. Here we investigated whether platelet TF expression is increased in a hypertensive status through a mechanism acting on megakaryocytes; the phenomenon could be modulated by antihypertensive drug as captopril; angiotensin (AngII) influences platelet TF expression. Methods: Spontaneously hypertensive stroke prone (SHRSP) rats received standard diet (StD) or a Japanese high-salt permissive diet (JpD). After 3 weeks, JpD animals were randomized to receive captopril or vehicle. Normotensive Wistar Kyoto (WKY) rats were used as controls. Cell-associated TF expression and activity were analyzed by flow cytometry and calibrated automated thrombogram, respectively. Results: Hypertensive StD-SHRSP showed an increased number of TF-positive platelets compared with normotensive WKY. After JpD administration, SHRSP developed severe hypertension and renal damage; the number of TF-positive megakaryocytes significantly increased compared with StD-SHRSP resulting in a higher number of TF-positive platelets with a faster kinetic of thrombin generation. These effects were reverted by captopril. Ex-vivo stimulation of platelets, isolated from normotensive WKY and from healthy individuals, with AngII induced a concentration-dependent increase of surface-associated TF expression. Conclusion: The current study shows for the first time that in hypertension the number of TF-positive megakaryocytes increases thus releasing in the circulation more platelets carrying a functionally active TF. AngII stimulates platelets to express TF.

AB - Objective: Hypertension is a well known risk factor for thrombotic events such as myocardial infarction and stroke. Platelets express tissue factor (TF), the key activator of blood coagulation and thrombus formation. The number of TF-positive platelets increases in pathological conditions characterized by thrombotic complications but whether this occurs in hypertension is unknown. Here we investigated whether platelet TF expression is increased in a hypertensive status through a mechanism acting on megakaryocytes; the phenomenon could be modulated by antihypertensive drug as captopril; angiotensin (AngII) influences platelet TF expression. Methods: Spontaneously hypertensive stroke prone (SHRSP) rats received standard diet (StD) or a Japanese high-salt permissive diet (JpD). After 3 weeks, JpD animals were randomized to receive captopril or vehicle. Normotensive Wistar Kyoto (WKY) rats were used as controls. Cell-associated TF expression and activity were analyzed by flow cytometry and calibrated automated thrombogram, respectively. Results: Hypertensive StD-SHRSP showed an increased number of TF-positive platelets compared with normotensive WKY. After JpD administration, SHRSP developed severe hypertension and renal damage; the number of TF-positive megakaryocytes significantly increased compared with StD-SHRSP resulting in a higher number of TF-positive platelets with a faster kinetic of thrombin generation. These effects were reverted by captopril. Ex-vivo stimulation of platelets, isolated from normotensive WKY and from healthy individuals, with AngII induced a concentration-dependent increase of surface-associated TF expression. Conclusion: The current study shows for the first time that in hypertension the number of TF-positive megakaryocytes increases thus releasing in the circulation more platelets carrying a functionally active TF. AngII stimulates platelets to express TF.

KW - angiotensin II

KW - antihypertensive drug

KW - blood pressure

KW - platelets

KW - stroke-prone rats

KW - tissue factor

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U2 - 10.1097/HJH.0000000000001702

DO - 10.1097/HJH.0000000000001702

M3 - Article

AN - SCOPUS:85046685628

VL - 36

SP - 1360

EP - 1371

JO - Journal of Hypertension

JF - Journal of Hypertension

SN - 0263-6352

IS - 6

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