Related Experiment Video
Updated: Sep 25, 2026
Characterizing Modulators of Protease-Activated Receptors with a Calcium Mobilization Assay Using a Plate Reader
Published on: May 24, 2024
Perindopril augments ecto-ATP diphosphohydrolase activity and enhances endothelial anti-platelet function in human
Yukio Kishi1, Seiko Ohta, Natsuko Kasuya
1Center for Preventive Medicine, Tokyo Kyosai Hospital, Tokyo, Japan. kishi.hsc@tkh.meguro.tokyo.jp
Insights
Angiotensin-converting enzyme inhibitors like perindopril enhance endothelial cells' ability to prevent platelet aggregation. This effect is mediated by increased ecto-ADPase activity and prostacyclin release, crucial for cardiovascular health.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Endothelial Cell Biology
Background:
- Angiotensin-converting enzyme inhibitors (ACEIs) are known to reduce thrombotic events in cardiovascular diseases.
- The precise mechanisms by which ACEIs exert these anti-thrombotic effects remain largely unknown.
Purpose of the Study:
- To investigate the in vitro effects of perindopril, an ACEI, on human umbilical vein endothelial cells (HUVEC).
- To determine how perindopril influences HUVEC's capacity to inhibit platelet aggregation.
Main Methods:
- Assessed platelet aggregation in the presence of HUVEC.
- Measured endothelial surface expression and activity of ecto-ATP diphosphohydrolase (ecto-ADPase, CD39).
- Investigated the release of prostacyclin and nitric oxide (NO) from HUVEC.
Main Results:
- Perindoprilat, the active metabolite of perindopril, significantly enhanced ecto-ADPase activity and prostacyclin release, improving HUVEC's anti-platelet aggregation ability.
- These beneficial effects were observed even in HUVEC activated with tumor necrosis factor-alpha (TNF-α), which normally impairs endothelial anti-platelet properties.
- Perindoprilat partially restored anti-platelet function in TNF-α-activated cells but did not reverse ICAM-1 upregulation; nitric oxide's role was minimal.
Conclusions:
- Perindoprilat augments endothelial anti-platelet aggregation capacity by boosting ecto-ADPase activity and prostacyclin release.
- This protective effect is maintained in activated endothelial cells, though perindoprilat does not reverse the underlying inflammatory process.
Objectives:
Recent clinical trials have demonstrated that angiotensin-converting enzyme inhibitors (ACEIs) reduce thrombotic events by unknown mechanisms in patients with atherosclerotic cardiovascular diseases.
Design:
We studied the in-vitro effects of perindopril, an ACEI, on the ability of human umbilical vein endothelial cells (HUVEC) to inhibit platelet aggregation.
Methods:
Platelet aggregation in the presence of HUVEC and endothelial surface expression and activities of ecto-ATP diphosphohydrolase (ecto-ADPase), CD39, were determined. The capability of HUVEC to release prostacyclin and nitric oxide (NO) was also investigated.
Results:
Perindoprilat (an active metabolite of perindopril) significantly enhanced the surface expression and activities of ecto-ADPase and prostacyclin release, resulting in enhancement of ability to inhibit platelet aggregation by HUVEC. These effects of perindoprilat were also observed in HUVEC activated by tumour necrosis factor (TNF)-alpha, which increased the expression of intracellular adhesion molecule-1 (ICAM-1), CD54, and, despite up-regulation of prostacyclin release, attenuated endothelial anti-platelet properties by decreasing ecto-ADPase activity. Perindoprilat partially restored this capability, but failed to reduce enhanced expression of ICAM-1. By contrast, the role of NO as a platelet inhibitor appeared minimal in HUVEC. Candesartan, an angiotensin II receptor (AT(1)) blocker, did not affect endothelial anti-platelet property.
Conclusions:
Perindoprilat was found to augment endothelial capability to inhibit platelet aggregation by increasing ecto-ADPase activity and prostacyclin release in HUVEC. This beneficial effect of perindoprilat appeared to be preserved in the activated cells exposed to TNF-alpha, although no evidence was found to support that it could reverse the inflammation process induced by cytokines.
Related Concept Videos
01:30Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
01:30Antihypertensive Drugs: Angiotensin II Receptor Blockers
01:28Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
01:23Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
01:18Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme (ECE). Of...
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System