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Platelets, vascular disease, and diabetes mellitus
1Department of Pathology, McMaster University, Hamilton, ON, Canada.
Insights
Diabetic platelets show increased hypersensitivity to agonists, contributing to enhanced atherosclerosis. These platelet changes may explain the higher risk of blood clots and vascular disease in diabetes.
Area of Science:
- Cardiovascular Medicine
- Endocrinology
- Hematology
Background:
- Diabetes mellitus significantly elevates the risk of atherosclerosis and associated thromboembolic events.
- Platelets play a crucial role in atherosclerosis by releasing substances that interact with injured blood vessels.
Purpose of the Study:
- To investigate the mechanisms by which platelets contribute to enhanced atherosclerosis in diabetes.
- To explore platelet hypersensitivity and activation alterations in diabetic patients.
Main Methods:
- In vitro studies assessing platelet sensitivity to agonists.
- Analysis of platelet surface receptors, membrane fluidity, and intracellular signaling pathways.
- Review of in vivo and animal studies on platelet activity in diabetes.
Main Results:
- Diabetic platelets exhibit hypersensitivity to agonists, linked to increased glycoprotein receptors and fibrinogen binding.
- Enhanced arachidonate pathway activation and increased thromboxane A2 formation were observed.
- Alterations in phosphoinositide turnover, calcium mobilization, and protein phosphorylation indicate heightened platelet activation.
Conclusions:
- Diabetic platelet hypersensitivity and altered activation mechanisms contribute to accelerated atherosclerosis.
- These platelet changes are potential drivers of increased cardiovascular complications in diabetes.
- Further in vivo research is needed to fully elucidate the role of platelet activity in diabetic vascular disease.
Abstract:
Diabetes is associated with increased risk for atherosclerosis and its thromboembolic complications. Theories about mechanisms of atherosclerosis in diabetes are similar to those in the nondiabetic population. Platelets contribute to atherosclerosis through effects on vessels by materials released from the platelets, which interact with injured or altered vessels. In diabetes, platelets could contribute to enhanced atherosclerosis through hypersensitivity to agonists at sites of vessel injury and increased release of materials from adherent platelets. Diabetic platelets are hypersensitive to agonists in vitro, and alterations in a number of mechanisms involved in platelet activation occur in these platelets, which could contribute to the hypersensitivity. These alterations include increased presence of glycoprotein receptors for agonists and adhesive proteins on the platelet surface, increased fibrinogen binding, decreased membrane fluidity, enhanced arachidonate pathway activation with increased thromboxane A2 formation, and increased phosphoinositide turnover leading to increased inositol trisphosphate production, Ca2+ mobilization, and protein phosphorylation. There is some evidence for increased platelet activity in vivo in diabetes, but it is unclear whether this reflects platelet hypersensitivity or increased platelet turnover on already diseased vessels. Studies in diabetic animals indicate greater interaction of platelets with injured vessels and incorporation into experimentally induced thrombi, but it is unclear if this reflects changes in platelets or other factors. These changes could be contributing to the enhanced atherosclerosis and its clinical complications in diabetic patients.