Endothelial Microparticles From Acute Coronary Syndrome Patients Induce Premature Coronary Artery Endothelial Cell Aging and Thrombogenicity: Role of the Ang II/AT1 Receptor/NADPH Oxidase-Mediated Activation of MAPKs and PI3-Kinase Pathways
Authors' conclusion
These findings indicate that endothelial-derived MPs from ACS patients induce premature endothelial senescence under atheroprone low shear stress and thrombogenicity through angiotensin II-induced redox-sensitive activation of mitogen-activated protein kinases and phosphoinositide 3-kinase/Akt.
Study context
- Population
- Primary porcine coronary artery endothelial cells (ECs) exposed to microparticles (MPs) from senescent ECs or from acute coronary syndrome (ACS) patients
- Participants
- 30 vs 4
- Comparison
- MPs from senescent ECs or ACS patients vs healthy volunteers
- ACSn = 30
- Healthy volunteersn = 4reference
- Outcome
- Endothelial senescence and thrombogenicity
Main finding
As reported in the abstract
- Passaging P1 to P4 induced senescence with progressive shedding of procoagulant MPs
- MPs from senescent P3 cells or ACS patients increased SA-β-gal activity, oxidative stress, MAPK and Akt phosphorylation, and p53, p21, p16 upregulation in P1 ECs
- Prosenescent effect of ACS MPs ex vivo only under low shear stress
- Depletion of endothelial-derived MPs from ACS patients reduced senescence induction
- Prosenescent MPs promoted EC thrombogenicity: tissue factor upregulation, procoagulant MP shedding, eNOS downregulation, reduced NO-mediated inhibition of platelet aggregation
- MPs had ACE activity and upregulated AT1 receptors and ACE in P1 ECs
- Losartan and MAPK or PI3-kinase inhibitors prevented MP-induced senescence
Original publication
Endothelial Microparticles From Acute Coronary Syndrome Patients Induce Premature Coronary Artery Endothelial Cell Aging and Thrombogenicity: Role of the Ang II/AT1 Receptor/NADPH Oxidase-Mediated Activation of MAPKs and PI3-Kinase Pathways. Circulation. Published 7 November 2016. doi:10.
Summarised from the published abstract; every number is checked against it