Structurally abnormal collagen fibrils in abdominal aortic aneurysm resist platelet adhesion

Background Platelet adhesion to the subendothelial collagen fibrils is one of the first steps in hemostasis. Understanding how structural perturbations in the collagen fibril affect platelet adhesion can provide novel insights into disruption of hemostasis in various diseases. We have recently ident...

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Bibliographic Details
Published in:Journal of thrombosis and haemostasis 2022-02, Vol.20 (2), p.470-477
Main Authors: Jones, Blain, Debski, Anna, Hans, Chetan P., Go, Michael R., Agarwal, Gunjan
Format: Article
Language:English
Subjects:
abdominal aortic aneurysm
Aneurysms
Aortic Aneurysm, Abdominal
Aortic aneurysms
Atomic force microscopy
blood platelets
Collagen
Collagen - chemistry
Extracellular Matrix
Fibrils
fluorescence
Hemostasis
Humans
Immunofluorescence
Microscopy
Microscopy, Atomic Force
Peptides - chemistry
Platelet Adhesiveness
Platelets
Protein Conformation
Thrombosis
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Summary:Background Platelet adhesion to the subendothelial collagen fibrils is one of the first steps in hemostasis. Understanding how structural perturbations in the collagen fibril affect platelet adhesion can provide novel insights into disruption of hemostasis in various diseases. We have recently identified the presence of abnormal collagen fibrils with compromised D‐periodic banding in the extracellular matrix remodeling present in abdominal aortic aneurysms (AAA). Objective In this study, we employed multimodal microscopy approaches to characterize how collagen fibril structure impacts platelet adhesion in clinical AAA tissues. Methods Ultrastructural atomic force microscopy (AFM) analysis was performed on tissue sections after staining with fluorescently labeled collagen hybridizing peptide (CHP) to recognize degraded collagen. Second harmonic generation (SHG) microscopy was used on CHP‐stained sections to identify regions of intact versus degraded collagen. Finally, platelet adhesion was identified via SHG and indirect immunofluorescence on the same tissue sections. Results Our results indicate that ultrastructural features characterizing collagen fibril abnormalities coincide with CHP staining. SHG signal was absent from CHP‐positive regions. Additionally, platelet binding was primarily localized to regions with SHG signal. Abnormal collagen fibrils present in AAA (in SHG negative regions) were thus found to inhibit platelet adhesion compared to normal fibrils. Conclusions Our investigations reveal how the collagen fibril structure in the vessel wall can serve as another regulator of platelet–collagen adhesion. These results can be broadly applied to understand the role of collagen fibril structure in regulating thrombosis or bleeding disorders.
ISSN:1538-7933
1538-7836
1538-7836
DOI:10.1111/jth.15576