1. Diabetes type 2: relationships between lysosomal exocytosis of circulating normal-sized platelets and in vitro alpha-thrombin-evoked platelet responses
- Author
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Edvardsson, Maria, Oweling, Magnus, Jaremo, Petter, Edvardsson, Maria, Oweling, Magnus, and Jaremo, Petter
- Abstract
Background/objective: Type 2 diabetes is a major risk factor for atherosclerotic disease. It is well agreed that the reactivity of diabetic platelets is increased but how platelet reactivity regulates is unknown. In our laboratory, density separated platelets have been investigated extensively and high- and low-density platelets circulate in an activated state. The density distribution of circulating platelets is altered in diabetes type 2 as well. We hypothesize that such platelets modify whole blood (WB) in vitro a-thrombin-evoked (10 mu M/mL) activity in type 2 diabetes. Thus, the study aims to identify features of circulating normal-sized density subpopulations affecting whole blood (WB) platelet reactivity in type 2 diabetes. Patients and methods: Patients with type 2 diabetes (n = 16) were enrolled. Their normal-sized platelets were divided into density subfractions (n = 16) using continuous polyvinylpyrrolidone-coated silica (Percoll (TM)) gradients (density span, 1.090-1.040 kg/L) containing prostaglandin E-1. The proportions (%) of such density-separated platelets expressing lysosomal-associated membrane protein 1 (LAMP-1) were analyzed using a flow cytometer. Further, determinations of WB alpha-thrombin-evoked (10 U/mL) surface LAMP-1 (an assessment of lysosomal release), the fibrinogen (a(IIb)beta(3)) receptor activity, annexin V (binds to exposed membrane phosphatidylserine), and mitochondrial transmembrane potentials (an estimate of organelle integrity) were performed. Surface LAMP-1 expressions of individual normal-sized platelet density subpopulations were stratified into equal-sized groups (n = 2) depending on reactivity, as judged from the alpha-thrombin-induced WB activity markers. Results: With some exceptions, the proportion of normal-sized circulating platelets showing spontaneous LAMP-1 was strongly associated with WB alpha-thrombin-evoked (10 U/mL) surface LAMP-1 and a(IIb)beta(3) receptor activity. LAMP-1-expressing normal-sized platelets als, Funding Agencies|OEstergoetland County Council, Sweden
- Published
- 2023
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