Mechanisms Determining Course and Outcome of Diabetic Patients Who Have Had Acute Myocardial Infarction

Aronson, Doron; Rayfield, Elliot J.; Chesebro, James H.

doi:10.7326/0003-4819-126-4-199702150-00006

Cited by 274 publications

(199 citation statements)

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“…Diabetic patients are at increased risk of cardiovascular disease and their prognosis after acute events is poorer than that of non-diabetic subjects [13]. The present study demonstrates that ischaemia-and growth factor-mediated mobilisation of progenitor cells is defective in diabetic rats.…”

Section: Discussionmentioning

confidence: 52%

Diabetes impairs progenitor cell mobilisation after hindlimb ischaemia–reperfusion injury in rats

et al. 2006

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Aims/hypothesis A reduction in the number of endothelial progenitor cells (EPCs) is considered a plausible cause of increased cardiovascular risk in diabetes mellitus. The aim of this study was to test the hypothesis that weak bone marrow mobilisation is responsible for the decrease in circulating EPCs in diabetes. Materials and methods We employed a model of hindlimb ischaemia-reperfusion (I/R) injury to study mobilisation of EPCs in control and streptozotocin diabetic rats. EPCs were defined by flow cytometry as Sca-1 + and Sca-1 + c-kit + peripheral blood cells and further characterised by the expression of CD31, von Willebrand factor and fetal liver kinase-1. Capillary density was evaluated by immunofluorescent staining of vWF. We also determined plasma levels of stromal cell-derived factor (SDF-1) and vascular endothelial growth factor (VEGF) by ELISA and muscle expression of hypoxia-induced factor (HIF-1α) by Western blotting.Results In control rats, EPCs showed a mobilisation curve within 7 days, while diabetic rats were completely unable to mobilise EPCs after I/R injury. As a consequence, diabetic rats showed no compensatory increase in muscle capillary density. Defective EPC mobilisation in diabetes was associated with altered release of SDF-1 and VEGF and inability to upregulate muscle HIF-1α. Both insulin administration and premedication with granulocyte-colony stimulating factor and stem cell factor led to partial recovery in postischaemic mobilisation of EPCs in diabetic rats. Conclusions/interpretation Defective ischaemia-induced bone marrow mobilisation of EPCs impedes compensatory angiogenesis in ischaemic tissues of diabetic animals. Growth factor administration together with blood glucose control may offer a rational therapeutic strategy for diabetic ischaemic syndromes.

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Section: Discussionmentioning

confidence: 52%

Diabetes impairs progenitor cell mobilisation after hindlimb ischaemia–reperfusion injury in rats

et al. 2006

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“…Recently, abciximab, a platelet glycoprotein IIb/IIIa inhibitor, was found to improve outcomes in diabetic patients after percutaneous transluminal coronary angioplasty (25). These observations suggest that hyperglycemia-induced platelet hyperaggregation and the subsequent release of PDGF may be one of the potential causes of the high frequency rates of restenosis in patients with diabetes (26,27). Inhibition of hyperglycemia-induced mitochondrial ROS overproduction may provide a new therapeutic strategy for the treatment of diabetic patients with acute coronary syndromes.…”

Section: Discussionmentioning

confidence: 99%

Hyperglycemia Potentiates Collagen-Induced Platelet Activation Through Mitochondrial Superoxide Overproduction

et al. 2001

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Alteration of platelet function contributes to microthrombus formation and may play an important role in the pathogenesis of diabetic micro-and macroangiopathies. However, the molecular mechanism for platelet dysfunction observed in patients with diabetes has not been fully elucidated. In this study, the direct effects of hyperglycemia on platelet function in vitro were investigated. Hyperglycemia increased reactive oxygen species generation in human platelets, and this effect was additive with that of collagen. Thenoyltrifluoroacetone (TTFA), an inhibitor of mitochondrial electron transport chain complex II, and carbonyl cyanide m-chlorophenylhydrazone (CCCP), an uncoupler of oxidative phosphorylation, completely prevented the effects of hyperglycemia, suggesting that reactive oxygen species arise from the mitochondrial electron transport chain. Hyperglycemia potentiated both platelet aggregation and the subsequent release of platelet-derived growth factor AB induced by a nonaggregating subthreshold concentration of collagen, which were also completely inhibited by TTFA or CCCP. Furthermore, hyperglycemia was found to inhibit protein tyrosine phosphatase (PTP) activity and increase phosphorylation of the tyrosine kinase Syk in platelets exposed to collagen. Hyperglycemia-induced PTP inhibition and Syk phosphorylation were found to be completely prevented by TTFA, CCCP, or Mn(III)tetrakis (4-benzoic acid) porphyrin, a stable cell-permeable superoxide dismutase mimetic. These results suggest that hyperglycemiainduced mitochondrial superoxide generation may play an important role in platelet dysfunction observed in patients with diabetes.

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“…While advances in PTCA like DES reduce some of these side effects so much so that in many patients with 1-or 2-vessel disease there may be hardly any difference between the two approaches, but for multivessel CAD, the difference may become crucial. In this subgroup, CABG is not only associated with fewer recurrent events or need for re-intervention but also better survival and thus studies after studies consistently demonstrated the superiority of CABG over PTCA, use of DES notwithstanding [4,5]. Similarly, in other situations of profoundly virulent atherosclerosis, CABG may be the best option.…”

Section: Effect Of Diabetes Mellitusmentioning

confidence: 98%

The shifting sands of coronary practice: from cardiologist’s amusement to a surgeon’s avocation

Mishra

2017

Indian J Thorac Cardiovasc Surg

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The field of coronary artery disease therapy has evolved over a period of time from medical therapy to coronary bypass surgery to interventional cardiology. However, none of the therapies have become obsolete and there is still place for optimal medical therapy, cardiac surgery as percutaneous interventions. The need of the hour is to develop an integrated multi-disciplinary approach popularly known as heart team approach at least for complex situations whether patient or lesion related.

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Mechanisms Determining Course and Outcome of Diabetic Patients Who Have Had Acute Myocardial Infarction

Cited by 274 publications

References 0 publications

Diabetes impairs progenitor cell mobilisation after hindlimb ischaemia–reperfusion injury in rats

Diabetes impairs progenitor cell mobilisation after hindlimb ischaemia–reperfusion injury in rats

Hyperglycemia Potentiates Collagen-Induced Platelet Activation Through Mitochondrial Superoxide Overproduction

The shifting sands of coronary practice: from cardiologist’s amusement to a surgeon’s avocation

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