Functional role of endothelial CXCL16/CXCR6-platelet–leucocyte axis in angiotensin II-associated metabolic disorders

Collado, Aida; Marqués, Patrice; Escudero, P.; Rius, Cristina; Domingo, Elena; Martínez-Hervás, Sergio; Real, José T.; Ascaso, Juan F.; Piqueras, Laura; Sanz, María-Jesús

doi:10.1093/cvr/cvy135

Cited by 30 publications

(27 citation statements)

References 41 publications

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“…Using PFA‐100, we found that the PFA‐100 CT of MetS patients was significantly shorter than that of the NC group (106 s vs 111 s, P < .05). This result provides evidence of platelet hyperactivation in MetS, similarly to previous studies 8‐11 . As we know, platelet activation is known to be associated with atherogenesis and cardiovascular morbidity 21 .…”

Section: Discussionsupporting

confidence: 88%

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Hypertriglyceridemia is associated with platelet hyperactivation in metabolic syndrome patients

Wang

et al. 2020

Int J Clin Pract

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Background and objectives Metabolic syndrome (MetS) is an independent risk factor for cardiovascular disease (CVD), in which platelet hyperactivation plays a pivotal role. The purpose of this study was to evaluate platelet function in MetS patients using Platelet Function Analyzer‐100 (PFA‐100) and to explore the risk factors for platelet hyperactivity in MetS. Subjects and methods We investigated participants who were enrolled for health check‐up in our department. Routine physical examinations and fasting blood sample tests were performed when participants visited the hospital. MetS was defined as ≥3 of the risk factors according to the Harmonised criteria: central obesity, hypertension (HP), hypertriglyceridemia, low high density lipoprotein cholesterol and hyperglycaemia. Participants were divided into a MetS group (≥3), normal control (NC) group (0) and non‐MetS group (1‐2) according to the numbers of the five risk factors. Platelet function was tested by PFA‐100, which measures the time taken for blood to occlude an aperture (closure time [CT]). All continuous data were compared using Student's t test or Mann‐Whitney U test according to the data distribution. Categorical data were compared using the chi‐square test. Logistic regression was used to investigate the independent risk marker for PFA‐100 CT values. Results A total of 831 participants (611 males and 220 females) was included in our subject. The MetS group had significantly shorter CT values compared with the NC group (106 (52‐181) s vs 111 (70‐210) s, P < .05) and the non‐MetS Group (106 (52‐181) s vs 113 (73‐197) s, P < .05). Higher body mass index, hypertriglyceridemia and HP were correlated with shorter CT values (P < .05). Logistic regression analyses indicated that hypertriglyceridemia was an independent risk marker for shorter PFA‐100 CT values (P < .05). Conclusion Our results indicate the presence of platelet hyperactivation in MetS patients and that hypertriglyceridemia is an independent risk marker for it. Triglyceride‐lowering treatment may reduce CVD risk in MetS individuals.

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Section: Discussionsupporting

confidence: 88%

“…Platelet activation has previously been reported in MetS 8‐11 . However, as far as we know, there are few studies evaluating platelet function in MetS subjects.…”

Section: Introductionmentioning

confidence: 93%

Hypertriglyceridemia is associated with platelet hyperactivation in metabolic syndrome patients

Wang

et al. 2020

Int J Clin Pract

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“…CXCL16 is the only ligand for the CXCR6 receptor. The CXCR6/CXCL16 axis has a rather bad press as its increased activity was shown to be associated with invasion of some cancers [38] and development of cardiometabolic disorders [39]. However, on the other hand, CXCL16 was demonstrated to be a critical mediator of muscle regeneration, which suppresses the development of fibrosis [40].…”

Section: Discussionmentioning

confidence: 99%

The Influence of Cell Source and Donor Age on the Tenogenic Potential and Chemokine Secretion of Human Mesenchymal Stromal Cells

Zarychta-Wiśniewska

Burdzińska

Zielniok

et al. 2019

Stem Cells International

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Background. Cellular therapy is proposed for tendinopathy treatment. Bone marrow- (BM-MSC) and adipose tissue- (ASC) derived mesenchymal stromal cells are candidate populations for such a therapy. The first aim of the study was to compare human BM-MSCs and ASCs for their basal expression of factors associated with tenogenesis as well as chemotaxis. The additional aim was to evaluate if the donor age influences these features. Methods. Cells were isolated from 24 human donors, 8 for each group: hASC, hBM-MSC Y (age≤45), and hBM-MSC A (age>45). The microarray analysis was performed on RNA isolated from hASC and hBM-MSC A cells. Based on microarray results, 8 factors were chosen for further evaluation. Two genes were additionally included in the analysis: SCLERAXIS and PPARγ. All these 10 factors were tested for gene expression by the qRT-PCR method, and all except of RUNX2 were additionally evaluated for protein expression or secretion. Results. Microarray analysis showed over 1,400 genes with a significantly different expression between hASC and hBM-MSC groups. Eight of these genes were selected for further analysis: CXCL6, CXCL12, CXCL16, TGF-β2, SMAD3, COLLAGEN 14A1, MOHAWK, and RUNX2. In the subsequent qRT-PCR analysis, hBM-MSCs showed a significantly higher expression than did hASCs in following genes: CXCL12, CXCL16, TGF-β2, SMAD3, COLLAGEN 14A1, and SCLERAXIS (p<0.05, regardless of BM donor age). In the case of CXCL12, the difference between hASC and hBM-MSC was significant only for younger BM donors, whereas for COLLAGEN 14A1—only for elder BM donors. PPARγ displayed a higher expression in hASCs compared to hBM-MSCs. In regard to CXCL6, MOHAWK, and RUNX2 gene expression, no statistically significant differences between groups were observed. Conclusions. In the context of cell-based therapy for tendinopathies, bone marrow appears to be a more attractive source of MSCs than does adipose tissue. The age of cell donors seems to be less important than cell source, although cells from elder donors show slightly higher basal tenogenic potential than do cells from younger donors.

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“…ARB treatment reduced the effects of CXCL1 and CXCL2 upregulation and increased oxidative stress [ [118] , [119] , [120] ]. CXCL16 is involved in Angiotensin II associated metabolic disorders and atherosclerosis, and its secretion is blocked by ARBs [ 121 , 122 ]. ARB treatment reduces MCP-1 upregulation during lung injury, inhibits monocyte recruitment and reduces lung fibrosis development [ 123 , 124 ].…”

Section: Discussionmentioning

confidence: 99%

Candesartan could ameliorate the COVID-19 cytokine storm

Elkahloun¹,

Saavedra²

2020

Biomedicine & Pharmacotherapy

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Functional role of endothelial CXCL16/CXCR6-platelet–leucocyte axis in angiotensin II-associated metabolic disorders

Abstract: CXCR6 expression on platelet-bound monocytes and CD8+ lymphocytes may constitute a new membrane-associated biomarker for adverse cardiovascular events. Moreover, pharmacological modulation of this axis may positively affect cardiovascular outcome in metabolic disorders linked to Ang-II.

Cited by 30 publications

References 41 publications

Hypertriglyceridemia is associated with platelet hyperactivation in metabolic syndrome patients

Hypertriglyceridemia is associated with platelet hyperactivation in metabolic syndrome patients

The Influence of Cell Source and Donor Age on the Tenogenic Potential and Chemokine Secretion of Human Mesenchymal Stromal Cells

Candesartan could ameliorate the COVID-19 cytokine storm

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