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Imatinib attenuates diabetes-associated atherosclerosis
Markus Lassila1, Terri J Allen, Zemin Cao
1Danielle Alberti Memorial Centre for Diabetes Complications, Vascular Division, Wynn Domain, Baker Heart Research Institute, Melbourne, Victoria, Australia.
Arteriosclerosis, Thrombosis, and Vascular Biology
|February 28, 2004
Summary
Diabetes accelerates atherosclerosis, but imatinib, a platelet-derived growth factor receptor antagonist, significantly reduced plaque development in diabetic mice. This suggests a new therapeutic approach for diabetic atherosclerosis.
Area of Science:
- Cardiovascular Research
- Endocrinology
- Pharmacology
Background:
- Diabetes mellitus accelerates atherosclerosis, a leading cause of mortality in diabetic patients.
- The precise molecular mechanisms linking diabetes to atherosclerosis are not fully elucidated.
- Platelet-derived growth factor (PDGF) is implicated in vascular diseases, but its role in diabetes-associated atherosclerosis is unknown.
Purpose of the Study:
- To investigate the involvement of PDGF-dependent pathways in diabetes-induced atherosclerosis.
- To evaluate the efficacy of PDGF receptor antagonism in mitigating diabetes-related atherosclerosis.
Main Methods:
- Streptozotocin-induced diabetes in apolipoprotein E knockout mice.
- Treatment with imatinib (a PDGF receptor tyrosine kinase inhibitor) or no treatment for 20 weeks.
- Assessment of aortic plaque area, PDGF-B expression, PDGF-beta receptor phosphorylation, and cytokine levels.
Main Results:
- Diabetes significantly increased aortic plaque area and expression of PDGF-B and its receptor.
- Diabetic mice exhibited elevated prosclerotic and proinflammatory cytokines.
- Imatinib treatment effectively prevented atherosclerotic lesion development and reduced cytokine overexpression.
Conclusions:
- PDGF signaling pathways are critically involved in diabetes-induced atherosclerosis.
- Targeting PDGF receptor tyrosine kinase with imatinib represents a potential therapeutic strategy.
- Imatinib may retard atherosclerosis development in the context of diabetes.