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 plateletimmune 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-1β, 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 plateletmonocyte 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.

BackgroundRecently, 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.MethodsAfter 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.ResultsSix months of vitamin D supplementation increases the serum vitamin D3 and total 25(OH)D levels from the baseline (p &lt; 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 &lt; 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 &lt; 0.05). Our ex vivo experiment confirms that a sufficient circulating level of vitamin D reduces platelet activation and platelet intracellular reactive oxygen species.ConclusionOur 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 RegistrationClinical Trial Registry of India: CTRI/2019/01/016921.

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.

Congenital pulmonary vein stenosis is a rare and interesting condition. This disease was classically believed to have an exceptionally bad prognosis. This article reviews the pathophysiology of the disease and advancements in diagnosis and management.