Chemokine Receptor 5, a Double-Edged Sword in Metabolic Syndrome and Cardiovascular Disease

Zhang, Zhongwen; Wang, Qiannan; Yao, Jinming; Zhou, Xiaojun; Zhao, Junyu; Zhang, Xiaoqian; Dong, Jianjun; Li, Lin

doi:10.3389/fphar.2020.00146

Cited by 23 publications

(20 citation statements)

References 100 publications

(145 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CCR5 is the main receptor for CCL5, although this chemokine can also bind with varying affinity to CCR1 and CCR3 [ 28 ]. CCR5 is expressed in macrophages, activated T-cells, natural killer cells, endothelial cells, and endothelial progenitor cells (EPCs), among others [ 29 ]. CCR5 participates in the regulation of the pro-inflammatory response by modulating the behavior, survival, and retention of immune cells in tissues [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

CCL5 Levels Predict Stroke Volume Growth in Acute Ischemic Stroke and Significantly Diminish in Hemorrhagic Stroke Patients

Serrano-Ponz

Ramalle-Gómara²,

Martı́nez

et al. 2022

IJMS

View full text Add to dashboard Cite

Stroke remains an important health challenge. Here, we study whether circulating chemokine (C-C motif) ligand 5 (CCL5) levels may predict clinical outcomes for stroke patients. A total of 100 consecutive stroke patients (36 acute ischemic and 64 hemorrhagic) were admitted to the stroke unit. Clinical history data and monitoring parameters were recorded. Blood serum was collected at days 0, 1, and hospital discharge to measure CCL5 levels by ELISA. Infarct or hemorrhagic volume, neurological severity (NIHSS), and functional prognosis (mRankin scale) were measured as clinical outcomes. CCL5 levels were lower in patients with hemorrhagic stroke than in patients with acute ischemic stroke. No differences were found between females and males in both types of stroke. Ischemic stroke patients whose infarct volume grew had lower CCL5 levels at day 0. Levels of CCL5 in ischemic and hemorrhagic patients were not associated with more severe symptoms/worse prognosis (NIHSS > 3; mRankin > 2) at admission or at 3 months. CCL5 could be used as a diagnostic marker to distinguish between ischemic and hemorrhagic strokes. Furthermore, CCL5 levels could predict the infarct volume outcomes in ischemic patients.

show abstract

Section: Introductionmentioning

confidence: 99%

CCL5 Levels Predict Stroke Volume Growth in Acute Ischemic Stroke and Significantly Diminish in Hemorrhagic Stroke Patients

Serrano-Ponz

Ramalle-Gómara²,

Martı́nez

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…Apart from viral control, CCR5 expression on immune cells is known to play a role in the development of atherosclerosis 7 , also in PLHIV 52 . Increased percentages of CCR5+ monocytes and CD8+ T cells were indeed found in asymptomatic PLHIV 6 months before a first episode of acute coronary syndrome compared to a matched control group that remained asymptomatic, suggesting an important role for CCR5 in the development of cardiovascular diseases 53 .…”

Section: Discussionmentioning

confidence: 99%

People with HIV have higher percentages of circulating CCR5+ CD8+ T cells and lower percentages of CCR5+ regulatory T cells

Eekeren

Matzaraki

Zhang

et al. 2022

Sci Rep

View full text Add to dashboard Cite

CCR5 is the main HIV co-receptor. We aimed to (1) compare CCR5 expression on immune cells between people living with HIV (PLHIV) using combination antiretroviral therapy (cART) and HIV-uninfected controls, (2) relate CCR5 expression to viral reservoir size and (3) assess determinants of CCR5 expression. This cross-sectional study included 209 PLHIV and 323 controls. Percentages of CCR5+ cells (%) and CCR5 mean fluorescence intensity assessed by flow cytometry in monocytes and lymphocyte subsets were correlated to host factors, HIV-1 cell-associated (CA)-RNA and CA-DNA, plasma inflammation markers and metabolites. Metabolic pathways were identified. PLHIV displayed higher percentages of CCR5+ monocytes and several CD8+ T cell subsets, but lower percentages of CCR5+ naive CD4+ T cells and regulatory T cells (Tregs). HIV-1 CA-DNA and CA-RNA correlated positively with percentages of CCR5+ lymphocytes. Metabolome analysis revealed three pathways involved in energy metabolism associated with percentage of CCR5+ CD8+ T cells in PLHIV. Our results indicate that CCR5 is differently expressed on various circulating immune cells in PLHIV. Hence, cell-trafficking of CD8+ T cells and Tregs may be altered in PLHIV. Associations between energy pathways and percentage of CCR5+ CD8+ T cells in PLHIV suggest higher energy demand of these cells in PLHIV.

show abstract

“…Neutralizing anti-CCL5 antibodies have provided a therapeutic benefit in a mouse model of chronic cardiac ischemia ( Montecucco et al, 2012 ). Nevertheless targeting CCR5 was not always effective in cardiovascular treatments because CCL5/CCR5 facilitates progenitor cell recruitment and promotes vascular endothelial cell repair ( Zhang et al, 2020 ). CCR5 signaling is reported to suppress inflammation and reduce adverse remodeling of the infarcted heart ( Dobaczewski et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

UTP Regulates the Cardioprotective Action of Transplanted Stem Cells Derived From Mouse Cardiac Adipose Tissue

Villamil

Roeck²,

Vanorlé³

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Adipose tissue is a source of stem cells with a high potential of differentiation for cell-based regenerative therapies. We previously identified mouse P2Y2, an ATP and UTP nucleotide receptor, as a regulator of adipogenic and endothelial differentiation of cardiac adipose-derived stem cells (cADSC). We investigated here the potential involvement of P2Y2 receptor in the cardioprotective action of undifferentiated cADSC transplantation in mouse ischemic heart. Transplantation of cADSC was realized in the periphery of the infarcted zone of ischemic heart, 3 days after left anterior descending artery ligation. A strong reduction of collagen stained area was observed 14 days after cADSC injection, compared to PBS injection. Interestingly, loss of P2Y2 expression totally inhibits the ability of transplanted cADSC to reduce cardiac fibrosis. A detailed gene ontology enrichment analysis was realized by comparing RNA-sequencing data obtained for UTP-treated wild type cASDC and UTP-treated P2Y2-null cASDC. We identified UTP target genes linked to extracellular matrix organization such as matrix metalloproteinases and various collagen types, UTP target genes related to macrophage chemotaxis and differentiation into pro-fibrotic foam cells, and a significant number of UTP target genes linked to angiogenesis regulation. More particularly, we showed that UTP regulated the secretion of CCL5, CXCL5, and CCL12 chemokines and serum amyloid apolipoprotein 3, in the supernatants of UTP-treated cADSC. Interestingly, CCL5 is reported as a key factor in post-infarction heart failure and in the reparative and angiogenic action of transplanted ADSC on ischemic tissue. We investigated then if a UTP-pretreatment of cADSC amplifies their effect on cardiac revascularization in mouse ischemic heart. Transplantation of cADSC was able to increase peri-infarct capillary density, 14 days after their injection. This beneficial effect on cardiac revascularization was enhanced by a UTP-pretreatment of cADSC before their transplantation, and not observed using P2Y2-null cADSC. Our data support that the efficacy of transplanted cADSC can be regulated by the release of inflammatory mediators such as extracellular nucleotides in the ischemic site. The present study highlights the P2Y2 receptor as a regulator of cADSC cardioprotective action, and as a potential target for the therapeutic use of undifferentiated cADSC in post-ischemic cardiac ischemia.

show abstract

Chemokine Receptor 5, a Double-Edged Sword in Metabolic Syndrome and Cardiovascular Disease

Cited by 23 publications

References 100 publications

CCL5 Levels Predict Stroke Volume Growth in Acute Ischemic Stroke and Significantly Diminish in Hemorrhagic Stroke Patients

CCL5 Levels Predict Stroke Volume Growth in Acute Ischemic Stroke and Significantly Diminish in Hemorrhagic Stroke Patients

People with HIV have higher percentages of circulating CCR5+ CD8+ T cells and lower percentages of CCR5+ regulatory T cells

UTP Regulates the Cardioprotective Action of Transplanted Stem Cells Derived From Mouse Cardiac Adipose Tissue

Contact Info

Product

Resources

About