The molecular understanding of the pathophysiological changes elicited by diabetes
in platelets may help in further elucidating the involvement of this pseudo-cell in
the increased risk of developing cardiovascular disease and thrombosis in diabetic
subjects. We aimed to investigate the differential characteristics of platelets from
diabetic patients and nondiabetic controls to unveil the molecular mechanisms behind
the increased platelet reactivity in diabetes. We compared platelets from diabetic
and control subjects by 2 dimensional-electrophoresis followed by mass spectrometry.
Changes in selected differential proteins were validated by immunoprecipitation assays
and western blot. Platelet aggregation was measured by light transmittance aggregometry
induced by collagen and ADP, and dynamic coagulation analysis of whole blood was measured
by thromboelastometry. We observed significant differences in proteins related to
platelet aggregation, cell migration, and cell homeostasis. Subjects with diabetes
showed higher platelet aggregation and thrombogenicity and higher contents of the
stress-related protein complex HSPA8/Hsp90/CSK2α than nondiabetic subjects. Changes
in the chaperones HSPA8 and Hsp90, and in CSK2α protein contents correlated with changes
in platelet aggregation and blood coagulation activity. In conclusion, the complex
HSPA8/Hsp90/CSK2α is involved in diabetes-related platelet hyperreactivity. The role
of the HSPA8/Hsp90/CSK2α complex may become a molecular target for the development
of future preventive and therapeutic strategies for platelet dysfunction associated
with diabetes and its complications.
Abbreviations
- BM bone marrow
- CVD cardiovascular disease
- CSK2α casein kinase 2α
- CFT clot formation time
- CT clotting time
- HSPA8 heat shock protein A8
- Hsp90 heat shock protein90
- IPA induced platelet aggregation
- LOESS local regression model
- MS mass spectrometry
- MALDI-TOF matrix-assisted laser desorption/ionization time-of-flight
- MCF maximum clot firmness
- PMF peptide mass fingerprinting
- PRP platelet-rich plasma
- PP1Cɣ protein phosphatase 1Cɣ
- RT room temperature
- 2DE two-dimensional electrophoresis
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Article info
Publication history
Published online: April 19, 2021
Accepted:
April 12,
2021
Received in revised form:
April 9,
2021
Received:
December 1,
2020
Footnotes
Featured New Investigator: Gemma Chiva-Blanch, PhD is currently working at the Endocrinology and Nutrition Laboratory of the CIBEROBN- IDIBAPS, Hospital Clínic of Barcelona, Spain.
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