RRC ID 27743
Author Hernández Vera R, Vilahur G, Ferrer-Lorente R, Peña E, Badimon L.
Title Platelets derived from the bone marrow of diabetic animals show dysregulated endoplasmic reticulum stress proteins that contribute to increased thrombosis.
Journal Arterioscler Thromb Vasc Biol
Abstract OBJECTIVE:Patients with diabetes mellitus have an increased risk of suffering atherothrombotic syndromes and are prone to clustering cardiovascular risk factors. However, despite their dysregulated glucose metabolism, intensive glycemic control has proven insufficient to reduce thrombotic complications. Therefore, we aimed to elucidate the determinants of thrombosis in a model of type 2 diabetes mellitus with cardiovascular risk factors clustering.
METHODS AND RESULTS:Intravital microscopy was used to analyze thrombosis in vivo in Zucker diabetic fatty rats (ZD) and lean normoglycemic controls. Bone marrow (BM) transplants were performed to test the contribution of each compartment (blood or vessel wall) to thrombogenicity. ZD showed significantly increased thrombosis compared with lean normoglycemic controls. BM transplants demonstrated the key contribution of the hematopoietic compartment to increased thrombogenicity. Indeed, lean normoglycemic controls transplanted with ZD-BM showed increased thrombosis with normal glucose levels, whereas ZD transplanted with lean normoglycemic controls-BM showed reduced thrombosis despite presenting hyperglycemia. Significant alterations in megakaryopoiesis and platelet-endoplasmic reticulum stress proteins, protein disulfide isomerase and 78-kDa glucose-regulated protein, were detected in ZD, and increased tissue factor procoagulant activity was detected in plasma and whole blood of ZD.
CONCLUSIONS:Our results indicate that diabetes mellitus with cardiovascular risk factor clustering favors BM production of hyperreactive platelets with altered protein disulfide isomerase and 78-kDa glucose-regulated protein expression that can contribute to increase thrombotic risk independently of blood glucose levels.
Volume 32(9)
Pages 2141-8
Published 2012-9-1
DOI 10.1161/ATVBAHA.112.255281
PII ATVBAHA.112.255281
PMID 22837468
MeSH Animals Blood Coagulation* Blood Coagulation Tests Blood Glucose / metabolism Blood Platelets / metabolism* Blood Platelets / pathology Bone Marrow Cells / metabolism* Bone Marrow Cells / pathology Bone Marrow Transplantation Diabetes Complications / blood Diabetes Complications / etiology* Diabetes Complications / pathology Diabetes Mellitus, Type 2 / blood Diabetes Mellitus, Type 2 / complications* Diabetes Mellitus, Type 2 / pathology Disease Models, Animal Endoplasmic Reticulum / metabolism* Endoplasmic Reticulum / pathology Endoplasmic Reticulum Stress* Green Fluorescent Proteins / biosynthesis Green Fluorescent Proteins / genetics Heat-Shock Proteins / metabolism* Platelet Activation Platelet Function Tests Protein Disulfide-Isomerases / metabolism Rats Rats, Transgenic Rats, Wistar Rats, Zucker Thromboplastin / metabolism Thrombopoiesis Thrombosis / blood Thrombosis / etiology* Thrombosis / pathology Time Factors
IF 6.604
Times Cited 26
Rats W-Tg(CAG-GFP)184Ys(strainID=525)