A calorie-restricted diet enriched with tree nuts and peanuts reduces the expression of CX3CR1 in peripheral blood mononuclear cells in patients with coronary artery disease

Author(s):  
Matin Ghanavati ◽  
Javad Nasrollahzadeh

Abstract. Background: The modification of the gut microbiome has been proposed to alter immune response which is a key driver in low-grade inflammation as well as metabolic markers. This study was conducted to determine the effects of a low-calorie diet with and without nuts on some gut bacterial abundance, metabolic markers, and gene expression in peripheral blood mononuclear cells (PBMCs) in stable coronary artery disease patients with overweight or obesity. Methods: Overweight or obese patients with stable coronary artery disease of both genders were randomly allocated to a nut-free calorie-restricted diet as 25% of energy deficit (CRD) or a CRD enriched with 39–60 gr/d of mixed nuts (CRDEN) for 8 weeks (32 patients in CRD and 35 patients in CRDEN). Mixed nuts consisted of equal amounts of unsalted pistachios, almonds, and peanuts. Microbiota analysis was performed by quantitative real-time polymerase chain reaction method on feces collected before and after the intervention, using primers targeting 16S ribosomal DNA of 4 different bacterial genera, including Bacteroides, Prevotella, Bifidobacterium, and Lactobacillus. We examined the plasma concentrations of glucose, insulin, adiponectin as well as expression of toll-like receptor-4 (TLR4) and fractalkine receptor (CX3CR1) in PBMCs. Results: A significant reduction in expression of CX3CR1 (p=0.04) and a tendency to lower expression of TLR4 in PBMCs (p=0.06) was observed in the CRDEN group at the end of the study compared to the CRD group. The abundance of fecal Prevotella also tended to increase in CRDEN compared to the CRD group (p=0.06). Plasma insulin and adiponectin had no significant changes. There was a positive correlation between fecal Prevotella abundance and plasma adiponectin at baseline (r=0.315, p=0.015) and the end of the study (r=0.380, p=0.003). Conclusion: Our results suggest that the inclusion of mixed tree nuts and peanuts in a low-calorie diet for 8 weeks led to a lower CX3CR expression in PBMCs in a cohort of overweight or obese patients with stable CAD. This finding provides another beneficial effect of diet supplemented with nuts on factors associated with inflammation. Trial registration: this clinical study has been registered at the clinical trial registration center (clinicaltrial.gov): NCT04078919 on September 6, 2019.

2019 ◽  
Vol 120 (01) ◽  
pp. 121-131 ◽  
Author(s):  
Jie Gao ◽  
Jia Liu ◽  
Ying Zhang ◽  
BaoYi Guan ◽  
Hua Qu ◽  
...  

AbstractPrethrombotic status (PTS) in patients with stable coronary artery disease (SCAD) increases the risk of coronary thrombosis. Accumulating evidences have indicated that micro-ribonucleic acids (miRNAs) may serve as promising biomarkers for SCAD patients with PTS. The present study aimed to identify the miRNA signature in SCAD patients with PTS and evaluated their diagnostic significance. In the screening phase, 32 differently expressed miRNAs (DEMs) in peripheral blood mononuclear cells (PBMCs) were detected in 35 SCAD patients compared with 5 healthy controls by microarray. MiRNA-gene network analysis was then performed, and 4 DEMs were selected for validation with reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) test in an independent cohort comprising 79 SCAD patients and 19 healthy controls. Compared with healthy controls, RT-qPCR test verified the upregulations of miR-34a-5p, miR-432–5p, and miR-370–3p detected by microarray; while the upregulation of miR-495–3p measured by RT-qPCR was not consistent with its low expression detected by microarray. Only miR-34a-5p and miR-495–3p were significantly upregulated in the PTS group compared with the non-PTS group (p < 0.01, p < 0.05). Receiver-operating characteristic (ROC) analysis showed that PBMCs-derived miR-34a-5p and miR-495–3p may discriminate PTS with the areas under the ROC curve (AUC) of 0.780 (confidence interval [CI]95% = 0.673–0.866) and 0.712 (CI95% = 0.599–0.808), respectively. The combination of miR-34a-5p and fibrinogen (FIB, a traditional biomarker for PTS) improved AUC to 0.885 (CI95% = 0.793–0.946) and showed added predictive ability compared with FIB, with an integrated discrimination improvement of 0.201 (p < 0.01). Therefore, the combination of miR-34a-5p and FIB may serve as an efficient tool for distinguishing PTS in SCAD patients.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Ida Unhammer Njerve ◽  
Sissel Åkra ◽  
Thomas W. Weiss ◽  
Svein Solheim ◽  
Reidun Øvstebø ◽  
...  

Background. Promising results regarding potential anti-inflammatory and antiatherosclerotic effects of gliptins have been reported. Our aim was to investigate whether saxagliptin treatment modifies expression of inflammatory markers, primarily in peripheral blood mononuclear cells (PBMCs) and in circulating leukocytes in patients with stable coronary artery disease (CAD) and T2DM. Methods. Patients (n=12) were randomized to saxagliptin 5 mg daily or placebo for 3 months. Samples were taken at baseline and end of study in fasting state prior to intake of medications. PBMCs were isolated and cryopreserved at −150°C until ex vivo exposed to 1 ng/mL of lipopolysaccharide (LPS) for 4 hours. Gene expression was performed with custom-designed TaqMan® Arrays and relative quantification by real-time PCR (RT-qPCR). Results. HbA1c was reduced in the saxagliptin-treated group compared to that in the change with placebo (p=0.042). In unstimulated PBMCs and in circulating leukocytes, we observed a significant increase in IL-10 expression in the saxagliptin group (p=0.043, both), significantly different from that in the placebo (p=0.009 and p=0.032, resp.). No between group differences in changes were observed in any of the selected proinflammatory markers. Conclusion. In our small cohort of patients with combined T2DM and CAD, a possible anti-inflammatory effect of saxagliptin, observed in the present study by upregulation of IL-10 in leukocytes, needs to be confirmed in larger studies.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Marlies P Noz ◽  
Siroon Bekkering ◽  
Laszlo Groh ◽  
Tim MJ Nielen ◽  
Evert JP Lamfers ◽  
...  

Atherosclerosis is the major cause of cardiovascular disease (CVD). Monocyte-derived macrophages are the most abundant immune cells in atherosclerotic plaques. In patients with atherosclerotic CVD, leukocytes have a hyperinflammatory phenotype. We hypothesize that immune cell reprogramming in these patients occurs at the level of myeloid progenitors. We included 13 patients with coronary artery disease due to severe atherosclerosis and 13 subjects without atherosclerosis in an exploratory study. Cytokine production capacity after ex vivo stimulation of peripheral blood mononuclear cells (MNCs) and bone marrow MNCs was higher in patients with atherosclerosis. In BM-MNCs this was associated with increased glycolysis and oxidative phosphorylation. The BM composition was skewed towards myelopoiesis and transcriptome analysis of HSC/GMP cell populations revealed enrichment of neutrophil- and monocyte-related pathways. These results show that in patients with atherosclerosis, activation of innate immune cells occurs at the level of myeloid progenitors, which adds exciting opportunities for novel treatment strategies.


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