Microvesicles from patients with acute coronary syndrome enhance platelet aggregation
Sam Kafian1, Håkan Wallén1, Bassem A Samad1
1Department of Clinical Sciences, Division of Cardiovascular Medicine, Danderyd Hospital, Karolinska Institutet , Stockholm , Sweden.
Abstract:
Microvesicles (MVs) released from leukocytes, platelets and endothelial cells are elevated in patients with acute coronary syndrome (ACS). In the present study, we assessed the potential pro-aggregatory properties of MVs obtained from ACS patients. Thus, we divided the patients into two groups based on clopidogrel-responsiveness, i.e. high on-treatment platelet reactivity (HPR; n = 16), and low or normal on-treatment platelet reactivity (non-HPR; n = 14), respectively. MVs from patients were obtained by high-speed centrifugation, and the pro-aggregatory effect of MVs added to fresh isolated platelets from healthy subjects were analyzed by 96-well microplate aggregometry. MVs from HPR patients significantly enhanced spontaneous platelet aggregation around two times more than MVs from non-HPR patients. The pro-aggregatory effect of three out of four MV phenotypes correlated to MV-concentrations as determined by flow cytometry. Furthermore, MVs from patients with diabetes mellitus (n = 9) had a stronger pro-aggregatory effect compared to MVs from those without diabetes (n = 21; p = .025 between groups). In conclusion, MVs from ACS patients with clopidogrel non-responsiveness enhance platelet aggregation, as do MVs from ACS patients with diabetes. Thus, MVs from patients with hyperreactive platelets boost platelet aggregation. Blocking MV-formation may reduce platelet hyperreactivity.
Insights
Microvesicles from acute coronary syndrome (ACS) patients with high on-treatment platelet reactivity (HPR) and diabetes significantly enhance platelet aggregation. Blocking microvesicle formation may reduce platelet hyperreactivity in ACS patients.
Area of Science:
- Cardiovascular Biology
- Hematology
- Biochemistry
Background:
- Microvesicles (MVs) from leukocytes, platelets, and endothelial cells are elevated in acute coronary syndrome (ACS).
- The pro-aggregatory properties of MVs in ACS patients require further investigation.
Purpose of the Study:
- To assess the pro-aggregatory potential of MVs from ACS patients.
- To compare MV effects between patients with high on-treatment platelet reactivity (HPR) and normal reactivity (non-HPR).
- To investigate the influence of diabetes on MV pro-aggregatory effects.
Main Methods:
- MVs were isolated from ACS patients using high-speed centrifugation.
- Pro-aggregatory effects were analyzed by adding MVs to platelets from healthy subjects using 96-well microplate aggregometry.
- MV concentrations were quantified by flow cytometry.
Main Results:
- MVs from HPR patients significantly enhanced spontaneous platelet aggregation compared to non-HPR patients.
- The pro-aggregatory effect of certain MV phenotypes correlated with MV concentration.
- MVs from diabetic ACS patients exhibited a stronger pro-aggregatory effect than those from non-diabetic patients.
Conclusions:
- MVs from ACS patients with clopidogrel non-responsiveness (HPR) and diabetes promote platelet aggregation.
- These findings suggest that MVs from patients with hyperreactive platelets contribute to increased platelet aggregation.
- Targeting MV formation could be a therapeutic strategy to reduce platelet hyperreactivity in ACS.
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