Platelet-derived sTLT-1 is associated with platelet-mediated inflammation in coronary artery disease patients.

The development of coronary artery disease (CAD) depends heavily on platelet activation, and inflammation plays a major role in all stages of atherosclerosis. Platelet-specific soluble triggering receptor expressed on myeloid cells like transcript 1 (sTLT-1) facilitate clot formation and have been linked to chronic inflammation. In this study, we explored the role of platelet-derived sTLT-1 in platelet-mediated inflammation in CAD patients. Plasma levels of sTLT-1 were measured using enzyme-linked immunosorbent assay in CAD patients (n = 163) and healthy controls (n = 99). Correlation analysis was performed to determine the circulatory sTLT-1 levels with platelet activation markers, immune cells, and inflammatory cytokines/chemokines. Increased plasma sTLT-1 levels were observed in CAD patients compared with those in healthy controls (p < 0.0001). A positive correlation was observed between sTLT-1 and platelet activation markers (P-selectin, PAC-1), CD14++ CD16- cells (classical monocytes), Natural killer T (NKT) cells, and platelet-immune cell aggregates with monocytes, neutrophils, dendritic cells, CD11c+ cells, and NKT cells. In contrast, a significant negative correlation was observed with CD8 cells. Furthermore, a significant positive correlation was observed between sTLT-1 and inflammatory markers (TNF-α, IL-1ß, IL-2, IL-6, IL-12p70, IL-18, CXCL-12, and CCL-11). Logistic regression analysis identified sTLT-1 and triglycerides as predictors of CAD. Receiver operating characteristic curve (ROC) analysis showed that sTLT-1 had a higher sensitivity and specificity for predicting CAD. Our findings suggest that platelet activation induces the release of sTLT-1 into the circulation in CAD patients, which aggregates with immune cells and enhances inflammatory responses.

Vitamin D Supplementation Modulates Platelet-Mediated Inflammation in Subjects With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Recently, our group identified increased platelet-mediated inflammation in type 2 diabetes (T2DM) patients, and it is a well-established risk factor for diabetes complications, particularly for the development of cardiovascular diseases (CVD). Furthermore, vitamin D is reported to play an important role in the modulation of platelet hyperactivity and immune function, although the effect of vitamin D on platelet-mediated inflammation is not well studied. Hence, we aimed to investigate the effect of vitamin D supplementation on platelet-mediated inflammation in T2DM patients. Methods: After screening a total of 201 subjects, our randomized, double-blind, placebo-controlled trial included 59 vitamin-D-deficient T2DM subjects, and the participants were randomly assigned to placebo (n = 29) or vitamin D3 (n = 30) for 6 months. Serum vitamin D metabolite levels, immunome profiling, platelet activation, and platelet-immune cell aggregate formation were measured at baseline and at the end of the study. Similarly, the serum levels of inflammatory cytokines/chemokines were assessed by a multiplex assay. Results: Six months of vitamin D supplementation increases the serum vitamin D3 and total 25(OH)D levels from the baseline (p < 0.05). Vitamin D supplementation does not improve glycemic control, and no significant difference was observed in immune cells. However, platelet activation and platelet immune cell aggregates were altered after the vitamin D intervention (p < 0.05). Moreover, vitamin D reduces the serum levels of IL-18, TNF-α, IFN-γ, CXCL-10, CXCL-12, CCL-2, CCL-5, CCL-11, and PF-4 levels compared to the baseline levels (p < 0.05). Our ex vivo experiment confirms that a sufficient circulating level of vitamin D reduces platelet activation and platelet intracellular reactive oxygen species. Conclusion: Our study results provide evidence that vitamin D supportive therapy may help to reduce or prevent the disease progression and cardiovascular risk in T2DM patients by suppressing oxidative stress and platelet-mediated inflammation. Clinical Trial Registration: Clinical Trial Registry of India: CTRI/2019/01/016921.

Circulatory hepcidin levels association with gestational diabetes mellitus: a meta-analysis of observational studies.

OBJECTIVES: Hepcidin is linked to glucose metabolism in women with gestational diabetes mellitus (GDM). This systematic review and meta-analysis was conducted to determine the association between hepcidin levels and GDM. A literature search was performed using different databases to identify potential studies investigating hepcidin association in GDM patients. The effect sizes were calculated based on the standardized mean difference (SMD) and Fisher's Z value with a 95% confidence interval (CI). KEY FINDINGS: Out of 827 articles, only 7 case-control studies satisfied the inclusion and exclusion criteria. The pooled SMD of circulatory hepcidin levels in GDM patients was considerably higher than normal pregnant women (SMD = 1.69; 95% CI, 0.86 to 2.53; P < 0.0001). This study also observed that hepcidin levels were positively correlated with ferritin levels (r = 0.264; Z = 0.27; P < 0.0001). Furthermore, a subgroup analysis of serum and plasma groups revealed significantly higher hepcidin levels in serum (SMD = 2.12; 95% CI, 0.44 to3.79; P = 0.001) than in the plasma group (SMD = 1.28; 95% CI, 0.32 to 2.2; I2 = 96%). SUMMARY: Our findings suggest that hepcidin levels may be elevated in GDM patients, making it a viable marker for GDM diagnosis, and regular monitoring of its levels could be helpful in aiding clinical decisions.