Polyhedrocytes in blood clots of type 2 diabetic patients with high cardiovascular risk: association with glycemia,oxidative stress and platelet activation

Background

Little is known about factors that affect the composition of contracted blood clots in specific diseases. We investigated the content of polyhedral erythrocytes (polyhedrocytes) formed in blood clots and its determinants in type 2 diabetes (T2D) patients.

Methods

In 97 patients with long-standing T2D [median HbA_1c, 6.4% (interquartile range 5.9–7.8)], we measured in vitro the composition of blood clots, including a clot area covered by polyhedrocytes using scanning electron microscopy and the erythrocyte compression index (ECI), defined as a ratio of the mean polyhedrocyte area to the mean native erythrocyte area. Moreover, plasma fibrin clot permeability (K_s), clot lysis time (CLT), thrombin generation, oxidative stress [total protein carbonyl (total PC), total antioxidant capacity and thiobarbituric acid reactive substances (TBARS)], and platelet activation markers were determined. The impact of glucose concentration on polyhedrocytes formation was assessed in vitro.

Results

Polyhedrocytes content in contracted clots was positively correlated with glucose (r?=?0.24, p?=?0.028), glycated hemoglobin (r?=?0.40, p?=?0.024), total cholesterol (r?=?0.22, p?=?0.044), TBARS (r?=?0.60, p?=?0.0027), P-selectin (r?=?0.54, p?=?0.0078) and platelet factor-4, PF4 (r?=?0.59, p?=?0.0032), but not with thrombin generation, platelet count, K_s or CLT. Patients who formed more polyhedrocytes (≥?10th percentile) (n?=?83, 85.6%) had higher glucose (+?15.7%, p?=?0.018), fibrinogen (+?16.6%, p?=?0.004), lower red blood cell distribution width (RDW, ??8.8%, p?=?0.034), reduced plasma clot density (??21.8% K_s, p?=?0.011) and impaired fibrinolysis (+?6.5% CLT, p?=?0.037) when compared to patients with lesser amount of polyhedrocytes (<?10th percentile). ECI and the content of polyhedrocytes were strongly associated with total PC (r?=?0.79, p?=?0.036 and r?=?0.67, p?=?0.0004, respectively). In vitro an increase of glucose concentration by 10 mmol/L was associated with 94% higher polyhedrocytes content (p?=?0.033) when compared to the baseline (7.1 mM). After adjustment for age, sex and fibrinogen, multiple regression analysis showed that RDW was the only independent predictor of polyhedrocytes content in T2D (OR?=?0.61, 95% CI 0.39–0.92).

Conclusions

Poor glycemic control, together with enhanced platelet activation and oxidative stress, increase the content of polyhedrocytes in blood clots generated in T2D patients.

     

Human expression patterns: qualitative and quantitative analysis of thrombospondin‐1 under physiological and pathological conditions

Thrombospondin‐1 (TSP‐1), a matricellular protein and one of the first endogenous anti‐angiogenic molecules identified, has long been considered a potent modulator of human diseases. While the therapeutic effect of TSP‐1 to suppress cancer was investigated in both research and clinical settings, the mechanisms of how TSP‐1 is regulated in cancer remain elusive, and the scientific answers to the question of whether TSP‐1 expressions can be utilized as diagnostic or prognostic marker for patients with cancer are largely inconsistent. Moreover, TSP‐1 plays crucial functions in angiogenesis, inflammation and tissue remodelling, which are essential biological processes in the progression of many cardiovascular diseases, and therefore, its dysregulated expressions in such conditions may have therapeutic significance. Herein, we critically analysed the literature pertaining to TSP‐1 expression in circulating blood and pathological tissues in various types of cancer as well as cardiovascular and inflammation‐related diseases in humans. We compare the secretion rates of TSP‐1 by different cancer and non‐cancer cells and discuss the potential connection between the expression changes of TSP‐1 and vascular endothelial growth factor (VEGF) observed in patients with cancer. Moreover, the pattern and emerging significance of TSP‐1 profiles in cardiovascular disease, such as peripheral arterial disease, diabetes and other related non‐cancer disorders, are highlighted. The analysis of published TSP‐1 data presented in this review may have implications for the future exploration of novel TSP‐1‐based treatment strategies for cancer and cardiovascular‐related diseases.     

Editorial focus: entering into the non-coding RNA era

Recent developments in high-throughput genotyping technologies have revealed the existence of several new classes of RNA that do not encode proteins but serve other cellular roles. To date, these non-coding RNAs (ncRNAs) have been shown to modulate both gene expression and genome remodeling, thus contributing to the control of both normal and disease-related cellular processes. The attraction of this research topic can be seen in the increasing number of submissions on ncRNAs to molecular biology journals, including Cellular Molecular Biology Letters (CMBL). As researchers attempt to deepen the understanding of the role of ncRNAs in cell biology, it is worth discussing the broader importance of this research.     

The Xerobranching Response Represses Lateral Root Formation When Roots Are Not in Contact with Water

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Conformations of methyl 3,4-dideoxy-DL-glyc-3-enopyranosides

The conformational equilibrium (°H₁ ?¹H°) has been established for 26 diastereoisomeric methyl 3,4-dideoxy-DL-glyc-3-enopyranosides on the basis of the coupling constant J_1,2. The position of equilibrium depends on the interplay of steric and polar factors. The concept of the allylic effect is useful in explaining some conformational phenomena.     

Crystal structures of all-alpha type membrane proteins

Integral membrane proteins are involved in a wide range of essential biological functions and the determination of their three-dimensional structures plays a central role in understanding their function. This review focuses on the structures of one class of integral membrane proteins: the functionally diverse all-alpha type membrane proteins. It gives an overview of all the structures determined by X-ray crystallography, describing each system and structure in turn. It shows that the structures of all-alpha type membrane proteins have made valuable contributions to understanding structure–function relationships in membrane proteins. These range from the first insights into the function of exciting individual proteins to an in-depth knowledge of protein function from entire biological systems.     

The role of behavioral conditioning in the cardiovascular adjustment to exercise

The purpose of this study was to determine if normal subjects could be trained to attenuate their cardiovascular responses while exercising on a bicycle ergometer. Ten young, untrained subjects exercised on a bicycle ergometer for five sessions. Half of the group was asked to slow their heart rate while exercising with heart rate feedback during exercise. Their average heart rate increase was 20% less than that of the control subjects, who exercised without feedback. The control subjects subsequently also received feedback during exercise and they were able to attenuate their heart rate responses comparably. Systolic blood pressure was not affected by feedback training. Changes in rate-pressure product paralleled changes in heart rate. These data show that autonomically mediated adjustments to exercise can be brought under experimental control through the use of appropriate behavioral techniques.