Reconstituted HDL improves platelet function in Type 2 diabetics
MedWire News: Study results show that reconstituted high-density lipoprotein (rHDL) therapy reduces the hyper-reactivity of platelets of patients with Type 2 diabetes, partly by lowering the cholesterol content of platelet membranes.
“Individuals with diabetes mellitus have an increased risk of cardiovascular disease and exhibit platelet hyper-reactivity, increasing their resistance to antithrombotic therapies such as aspirin and clopidogrel,” explain researchers.
“As a consequence, more potent antiplatelet therapeutic strategies are increasingly being used to reduce thrombotic complications in diabetes mellitus; however, these approaches have minimal impact on atherosclerotic lesions themselves, leading to persistent plaque instability.”
Anna Calkin (Baker IDI Heart and Diabetes Institute, Melbourne, Australia) and colleagues assigned 17 individuals with Type 2 diabetes to receive an infusion of placebo (n=10) or rHDL (n=7; CSL-111; 20 mg/kg/h) for 4 hours.
The rHDL group had a 1.4-fold increase in plasma HDL cholesterol levels from baseline to 4 hours. Platelets from these individuals following the infusions also had a more than 50% reduction in their aggregation response to multiple agonists compared with controls.
In an additional in vitro study of platelets from healthy volunteers, the inhibitory effects of rHDL on platelet function were shown to be time and dose dependent, and resulted in a widespread weakening of platelet function and a more than 50% reduction in formation of thrombi.
The researchers say that the isolated phospholipid component of rHDL, which enhances the release of cholesterol from platelets and reduces the lipid content of the cell membranes, is at least partly responsible for this effect.
Of note, the apolipoprotein A-I component of rHDL had little effect on platelet function or reduction of platelet cholesterol content.
“The greater platelet inhibitory properties of rHDL compared with native HDL suggest that agents that increase pre–B-HDL particles would have the greatest efficacy with respect to reducing platelet reactivity,” comment Calkin et al.
They conclude in the journal Circulation: “Investigations to determine whether rHDL infusions or long-term HDL-raising agents confer additional benefits to current antithrombotic agents without adversely affecting hemostasis are required.
“The present findings add a new dimension to the known antiatherosclerotic actions of reconstituted HDL to provide a rationale for HDL-raising therapies as novel antithrombotic agents.”
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By Helen Albert