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

Johny, Ebin; Bhaskar, Pathoori; Alam, Jahangir; Kuladhipati, Indra; Das, Rupam; Adela, Ramu

doi:10.2147/jir.s326716

Cited by 10 publications

(10 citation statements)

References 60 publications

(67 reference statements)

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“…There is abundant evidence supporting that chronic in ammation, marked by increased levels of in ammatory cytokines, plays a crucial role in the pathophysiology of T2DM. However, the mechanisms are still not fully understood [17][18][19]. Increased concentrations of circulating in ammatory cytokines may augment the risk of metabolic disorders as well as increase pancreatic islet macrophage in ltration and apoptosis of β cell.…”

Section: Discussionmentioning

confidence: 99%

Comparison of changes in adipokine and inflammatory cytokine levels in patients with newly diagnosed type 2 diabetes treated with exenatide, insulin, or pioglitazone: a post-hoc study of the CONFIDENCE trial

Yang

Deng

et al. 2023

Preprint

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Purpose Adipokines and inflammatory cytokines (ADICs) play important roles in type 2 diabetes mellitus (T2DM). This study aimed to compare the changes of ADIC levels (ΔADICs) in patients with newly diagnosed T2DM treated with different antihyperglycemic agents, and further investigate the impact of these changes on metabolic indices, β-cell function and insulin resistance (IR). Methods Four hundred and sixteen patients with newly diagnosed T2DM from 25 centers in China randomly received 48-week intervention with exenatide, insulin or pioglitazone. Anthropometric and laboratory data, indices of β-cell function and IR, and levels of AIDCs, including interleukin-1 beta (IL-1β), interferon-gamma (IFN-γ), leptin, and fibroblast growth factor 21 (FGF21) were detected at baseline and the end of the study. Results In total, 281 participants (68% male, age: 50.3 ± 9.4 years) completed the study. After 48- week treatment, LgIL-1β and LgIFN-γ were significantly decreased with exenatide treatment (P < 0.001 and P = 0.001, respectively), but increased with insulin (P = 0.009 and P = 0.026, respectively). However, pioglitazone treatment had no impact on ADICs. No significant change in Lgleptin or LgFGF21 was detected with any of the treatments. After adjustment for baseline values and changes of body weight and HbA1c, significant differences were seen between the exenatide group and the insulin group and between the exenatide group and the pioglitazone group for both ΔLgIL-1β (P = 0.033 and P < 0.001, respectively) and ΔLgIFN-γ (P = 0.040 and P < 0.001, respectively). Multiple linear regression analysis indicated that Δweight was associated with ΔLgIL-1β (β = 0.753; 95% CI, 0.137–1.369; P = 0.017). After adjusting for treatment effects, Δweight was also found to be correlated with ΔLgFGF21 (β = 1.097; 95%CI, 0.250–1.944; P = 0.012). Furthermore, ΔLgHOMA-IR was associated with ΔLgleptin, both before (β = 0.085; 95%CI, 0.008–0.162; P = 0.030) and after (β = 0.078; 95%CI, 0.008–0.147; P = 0.029) adjusting for treatment effects. ΔLgHOMA-IR was significantly associated with ΔLgIL-1β before (β = 0.067; 95%CI, 0.006–0.127; P = 0.030), but not after (P = 0.513), adjusting for treatment effects. Conclusion Exenatide treatment led to significant changes of inflammatory cytokines levels (IL-1β and IFN-γ), but not adipokines (leptin and FGF21), in newly diagnosed T2DM patients. The exenatide-mediated improvement in weight and IR may be associated with a decrease in inflammatory cytokine levels.

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Section: Discussionmentioning

confidence: 99%

Comparison of changes in adipokine and inflammatory cytokine levels in patients with newly diagnosed type 2 diabetes treated with exenatide, insulin, or pioglitazone: a post-hoc study of the CONFIDENCE trial

Yang

Deng

et al. 2023

Preprint

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“…The flow cytometry analysis was performed to measure platelet activation, detect immunome profiling, and perform platelet- immune cell aggregate analysis following the protocol described in our previously reported study (3). Briefly, blood was collected by venepuncture in acid citrate dextrose (BD Vacutainer ® ) tubes for all the flow cytometry experiments and processed for analysis within 2 h of blood collection.…”

Section: Flow Cytometry Analysismentioning

confidence: 99%

“…Immunome profiling and platelet-immune cell aggregates were measured, as mentioned in our previous article (3). Briefly, whole blood was lysed, and cells were suspended in PBS with 1% w/v bovine serum albumin.…”

Section: Immunome Profiling and Measurement Of Platelet-immune Cell A...mentioning

confidence: 99%

“…Platelet activation and platelet-mediated inflammation are other critical factors implicated in the pathogenesis of coronary artery disease in type 2 diabetes patients. Recently, our group has shown that hyperglycemia in type 2 diabetes causes platelet activation; aggregation further contributes to systemic inflammation and the complexity of both type 2 diabetes and the development of cardiovascular diseases (3).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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 < 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.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.

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“…Coronary artery disease (CAD), a chronic inflammatory immune disease, is one of the leading causes of heart failure and death globally ( 1 , 2 ). It is characterized by plaque accumulation with the involvement of immune cells and cytokines ( 3 , 4 ). The mechanism of CAD has been extensively researched.…”

Section: Introductionmentioning

confidence: 99%

The relationship between soluble lymphocyte activation gene-3 and coronary artery disease

Xiong

Duan

Zhou

et al. 2022

Front. Cardiovasc. Med.

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BackgroundSoluble lymphocyte activation gene 3 (sLAG3) may be used for diagnosis or prognosis in various diseases. However, the relationship between sLAG3 and coronary artery disease (CAD) are still unclear. This study aimed to investigate the levels of sLAG3 in patients with CAD, and its potential clinical association with the disease.MethodsA total of 66 subjects (49 patients with CAD and 17 control subjects without CAD) were enrolled. The sLAG3 level was measured using enzyme-linked immunosorbent assay (ELISA) kits. Clinical variables included demographics, biochemical markers, coronary angiography status, and ejection fraction of the heart (EF) were collected, and Gensini scores were calculated. LAG3 gene data was extracted from three datasets (GSE23561, GSE61144, GSE60993) in Gene Expression Omnibus (GEO) to compare differential expression between CAD and control subjects.ResultsThe sLAG3 level was significantly lower in the CAD vs. the controls (P < 0.05), and negatively associated with CAD [odds ratio (OR): 0.212, 95% confidential interval (CI): 0.060–0.746, P < 0.05]. Furthermore, the area under the curve (AUC) of sLAG3 level was significant (P < 0.05). The sLAG3 level in subjects with body mass index (BMI) ≥ 24 kg/m2 was lower compared to those with BMI < 24 kg/m2 (P < 0.05). The sLAG3 level was also negatively associated with BMI and diabetes mellitus (P < 0.05), though not associated with the Gensini scores or EF (P > 0.05). Lastly, the LAG3 gene expression in peripheral whole blood of patients with CAD were down-regulated compared to healthy controls (P < 0.05).ConclusionThe sLAG3 level was negatively associated with the occurrence but not severity of CAD. Meanwhile, the sLAG3 was negatively associated with BMI and diabetes mellitus, suggesting the reduced sLAG3 might be a novel risk factor for developing CAD.

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

Cited by 10 publications

References 60 publications

Comparison of changes in adipokine and inflammatory cytokine levels in patients with newly diagnosed type 2 diabetes treated with exenatide, insulin, or pioglitazone: a post-hoc study of the CONFIDENCE trial

Comparison of changes in adipokine and inflammatory cytokine levels in patients with newly diagnosed type 2 diabetes treated with exenatide, insulin, or pioglitazone: a post-hoc study of the CONFIDENCE trial

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

The relationship between soluble lymphocyte activation gene-3 and coronary artery disease

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