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.

Platelet Mediated Inflammation in Coronary Artery Disease with Type 2 Diabetes Patients.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a well-established risk factor for the development of atherosclerotic coronary artery disease. Platelet hyperactivity and inflammation are associated with the development of coronary artery disease (CAD) in T2DM patients. We investigated the status of immune cells, platelet activation, and platelet-immune cell interactions in T2DM_CAD patients. METHODOLOGY: The study population consisted of four groups of subjects, healthy control (CT, n = 20), T2DM (n = 44), CAD (n = 20) and T2DM_CAD (n = 38). Platelet activation, immunome profiling and platelet-immune cell interactions were analysed by flow cytometry. The circulatory levels of inflammatory cytokines/chemokines were assessed using multiplex assay. RESULTS: Increased platelet activation and increased platelet-immune cell aggregate formation were observed in T2DM and T2DM_CAD groups compared to the control and CAD groups (p < 0.05). Our immunome profile analysis revealed, altered monocyte subpopulations and dendritic cell populations in T2DM, CAD and T2DM_CAD groups compared to the control group (p < 0.05). Furthermore, significantly increased IL-1ß, IL-2, IL-4, IL-6, IL-8, IL12p70, IL-13 IL-18, CCL2, and decreased CXCL1, CCL5 levels were observed in T2DM_CAD group compared to the control group. Our ex-vivo study increased platelet-monocyte aggregate formation was observed upon D-glucose exposure in a time and concentration dependent manner. CONCLUSION: Our data suggests that T2DM, CAD and T2DM_CAD are associated with altered immune cell populations. Furthermore, it has been confirmed that hyperglycemia induces platelet activation and forms platelet-immune cell aggregation which may lead to the release of inflammatory cytokines and chemokines and contribute to the complexity of CAD and type 2 diabetes.

Spontaneous recovery of complete atrioventricular block complicating acute anterior wall ST elevation myocardial infarction.

BACKGROUND: Complete atrioventricular block complicating acute anterior wall ST elevation myocardial infarction (MI) is classically considered one of the worst prognostic indicators. METHODS: We present the case of a gentleman who developed complete atrioventricular block during the course of acute anterior wall ST elevation MI, and had spontaneous resolution of the same. Mechanisms of spontaneous resolution of complete atrioventricular block in the setting of acute MI are discussed. Attention is drawn to a subgroup of patients, albeit a minority, who have a better prognosis owing to reversible causes than classically expected and seen. RESULTS: Clinical features suggested that this patient had reocclusion of the infarct-related artery after thrombolysis on presentation and spontaneous reperfusion. CONCLUSION: Coronary angiography provides invaluable information for decision making in such clinical scenarios. Complete atrioventricular block due to reversible ischaemia produced by reocclusion of an infarct-related artery should be reversible by percutaneous coronary angioplasty of the infarct-related artery. We suggest that reversible causes be considered before attributing atrioventricular block to irreversible damage, which would require a permanent pacemaker implantation. This would be more significant in most of the developing world, where resources are scarce.

Successful percutaneous endovascular management of acute post-traumatic superior mesenteric artery dissection using a transradial approach.

Acute aortic dissection extending into the superior mesenteric artery (SMA) following a blunt trauma is an extremely rare complication. We report a case of acute post-traumatic SMA dissection presented with an acute abdominal syndrome. Computed tomographic angiography and arteriography allowed a rapid diagnosis and urgent percutaneous endovascular intervention through transradial route. This approach saved a major surgical intervention and related morbidity.

Management of guidewire-induced coronary artery perforations through transradial route - A simple approach.

We describe two cases of guidewire-induced Type-3 coronary artery perforations leading to pericardial tamponade treated successfully through a transradial approach using polyvinyl alcohol particles. This can be an effective, alternative, simplistic approach in the management of distal coronary artery perforations with hemodynamic compromise otherwise requiring surgical intervention.