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Enhanced GPVI-dependent platelet pro-adhesive activity in patients with advanced coronary artery disease
Farshad Heydari1, Ehteramolsadat Hosseini1, Faranak Kargar2,3
1Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.
Insights
Patients with advanced coronary artery disease (CAD) show increased platelet adhesion, linked to higher GPVI receptor expression. These findings highlight a prothrombotic state and suggest platelet indices may serve as diagnostic markers.
Area of Science:
- Cardiovascular Biology
- Hematology
- Platelet Physiology
Background:
- Platelet activation is central to coronary artery disease (CAD), involving proaggregatory and proinflammatory states.
- The proadhesive phenotype, mediated by GPVI and integrin α₂β₁, is crucial in CAD pathogenesis but underexplored in advanced stages.
- Limited insight exists into platelet adhesion receptor expression and function in patients with advanced CAD undergoing coronary artery bypass grafting (CABG).
Purpose of the Study:
- To comprehensively assess adhesion receptor expression (GPVI, α₂β₁) and collagen-dependent platelet adhesion in advanced CAD patients.
- To compare these parameters between CAD patients scheduled for CABG and healthy controls.
- To investigate the correlation between platelet adhesion, receptor expression, and platelet indices.
Main Methods:
- Flow cytometry was used to analyze GPVI, integrin α₂β₁, and P-selectin expression on platelets from 20 advanced CAD patients and healthy controls.
- Collagen-dependent platelet adhesion and spreading were evaluated using immunofluorescence microscopy.
- Correlations were established between adhesion parameters, receptor expression, and platelet indices (MPV, PDW).
Main Results:
- Advanced CAD patients exhibited significantly higher expression of GPVI and P-selectin, but not α₂β₁, compared to controls.
- Increased platelet adhesion and spreading on collagen matrices were observed in CAD patients.
- Platelet functional activity strongly correlated with GPVI expression and platelet indices like MPV and PDW.
Conclusions:
- This study reveals a heightened proadhesive platelet phenotype in advanced CAD, associated with increased GPVI expression and specific platelet indices.
- This proadhesive state may elevate the risk of pre-CABG prothrombotic complications.
- Platelet indices (MPV, PDW) show potential as indirect surrogate markers for platelet adhesive potential, with the adhesion profile demonstrating high diagnostic accuracy for CAD.
Abstract:
Platelet activation is a hallmark feature of coronary artery disease (CAD), characterized by a proaggregatory and proinflammatory state. However, the proadhesive phenotype, mediated by the collagen receptors GPVI and integrin α₂β₁, seems to be critically essential in the pathogenesis of disease yet underexplored in advanced CAD patients. Given the limited insight into this area, we aimed, for the first time, to comprehensively assess the expression of adhesion receptors, as well as the collagen-dependent adhesion of platelets, in CAD patients candidates for CABG (Advanced CAD) compared to healthy controls. Twenty CAD patients scheduled for CABG surgery, selected using strict exclusion criteria, and healthy controls were analyzed for expression of GPVI, integrin α₂β₁, and P-selectin via flow cytometry. Collagen-dependent platelet adhesion and spreading under static conditions were evaluated by immunofluorescence microscopy, which was correlated with GPVI expression and platelet indices. CAD patients exhibited higher levels of GPVI and P-selectin expression, but not α2β1, along with increased platelet adhesion and spreading on a collagen matrix. Platelet functional activity was strongly linked to GPVI expression and platelet indices, including MPV and PDW. The study presented here for the first time exhibited the higher proadhesive function in advanced CAD, which significantly correlates with platelet indices. These findings indicate that a sustained proadhesive state may increase the risk of prothrombotic complications before CABG, while the indices themselves may serve as indirect surrogate markers of platelet adhesive potential. Moreover, ROC curve analysis confirmed the high sensitivity and specificity of the adhesion profile in discriminating CAD patients from healthy controls.
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