Impact of angiotensin-converting enzyme inhibition on platelet Tissue Factor expression in stroke-prone rats

Published: 17 Sep 2019 | Version 1 | DOI: 10.17632/kn87z448d3.1
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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: 1) platelet TF expression is increased in a hypertensive status through a mechanism acting on megakaryocytes; 2) the phenomenon could be modulated by anti-hypertensive drug as captopril; 3) angiotensin influences platelet TF expression.
Methods: SHRSP rats received standard diet (StD) or a 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 platelet compared to normotensive WKY. After JpD administration, SHRSP developed severe hypertension and renal damage; the number of TF-positive megakaryocytes significantly increased compared to 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 subjects, with angiotensin induced a concentration-dependent increase of surface-associated TF expression.
Conclusion: This 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. Angiotensin stimulates platelets to express TF.

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  • Version 1

    2019-09-17

    Published: 2019-09-17

    DOI: 10.17632/kn87z448d3.1

    Cite this dataset

    Camera, Marina (2019), “Impact of angiotensin-converting enzyme inhibition on platelet Tissue Factor expression in stroke-prone rats”, Mendeley Data, v1 http://dx.doi.org/10.17632/kn87z448d3.1

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