scholarly journals Atypical Roles of the Chemokine Receptor ACKR3/CXCR7 in Platelet Pathophysiology

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 213
Author(s):  
Madhumita Chatterjee
Keyword(s):  
Cardiac Fibroblasts ◽  
Surface Expression ◽  
Endothelial Lining ◽  
Platelet Surface ◽  
Therapeutic Implications ◽  
Coronary Syndrome ◽  
Regulatory Impact ◽  
Chemokine Cxcl12 ◽  
Ischemic Episode ◽  
Artery Disease

The manifold actions of the pro-inflammatory and regenerative chemokine CXCL12/SDF-1α are executed through the canonical GProteinCoupledReceptor CXCR4, and the non-canonical ACKR3/CXCR7. Platelets express CXCR4, ACKR3/CXCR7, and are a vital source of CXCL12/SDF-1α themselves. In recent years, a regulatory impact of the CXCL12-CXCR4-CXCR7 axis on platelet biogenesis, i.e., megakaryopoiesis, thrombotic and thrombo-inflammatory actions have been revealed through experimental and clinical studies. Platelet surface expression of ACKR3/CXCR7 is significantly enhanced following myocardial infarction (MI) in acute coronary syndrome (ACS) patients, and is also associated with improved functional recovery and prognosis. The therapeutic implications of ACKR3/CXCR7 in myocardial regeneration and improved recovery following an ischemic episode, are well documented. Cardiomyocytes, cardiac-fibroblasts, endothelial lining of the blood vessels perfusing the heart, besides infiltrating platelets and monocytes, all express ACKR3/CXCR7. This review recapitulates ligand induced differential trafficking of platelet CXCR4-ACKR3/CXCR7 affecting their surface availability, and in regulating thrombo-inflammatory platelet functions and survival through CXCR4 or ACKR3/CXCR7. It emphasizes the pro-thrombotic influence of CXCL12/SDF-1α exerted through CXCR4, as opposed to the anti-thrombotic impact of ACKR3/CXCR7. Offering an innovative translational perspective, this review also discusses the advantages and challenges of utilizing ACKR3/CXCR7 as a potential anti-thrombotic strategy in platelet-associated cardiovascular disorders, particularly in coronary artery disease (CAD) patients post-MI.

scholarly journals Atypical Roles of the Chemokine Receptor ACKR3/CXCR7 in Platelet Pathophysiology

2021 ◽  
Author(s):  
Madhumita Chatterjee
Keyword(s):  
Myocardial Infarction ◽  
Surface Expression ◽  
Endothelial Lining ◽  
Platelet Surface ◽  
Therapeutic Implications ◽  
Regulatory Impact ◽  
Chemokine Cxcl12 ◽  
Ischemic Episode ◽  
Artery Disease ◽  
Platelet Functions

The manifold actions of the pro-inflammatory and regenerative chemokine CXCL12/SDF-1α are executed through the canonical GProteinCoupledReceptor CXCR4, and the non-canonical ACKR3/CXCR7. Platelets express CXCR4, ACKR3/CXCR7, and are a vital source of CXCL12/SDF-1α themselves. In recent years, a regulatory impact of the CXCL12-CXCR4-CXCR7 axis on platelet biogenesis i.e. megakaryopoiesis, thrombotic and thrombo-inflammatory ac-tions have been revealed through experimental and clinical studies. Platelet surface expression of ACKR3/CXCR7 is significantly enhanced following myocardial infarction (MI) in acute coro-nary syndrome (ACS) patients, also associated with improved functional recovery and progno-sis. The therapeutic implications of ACKR3/CXCR7 in myocardial regeneration and improved recovery following an ischemic episode, are well documented. Cardiomyocytes, cardi-ac-fibroblasts, endothelial lining of the blood vessels perfusing the heart, besides infiltrating platelets and monocytes, all express ACKR3/CXCR7. This review recapitulates ligand induced differential trafficking of platelet CXCR4-ACKR3/CXCR7 affecting their surface availability, and in regulating thrombo-inflammatory platelet functions and survival through CXCR4 or ACKR3/CXCR7. It emphasizes the pro-thrombotic influence of CXCL12/SDF-1α exerted through CXCR4, as opposed to the anti-thrombotic impact of ACKR3/CXCR7. Offering an innovative translational perspective, this review also discusses the advantages and challenges of utilizing ACKR3/CXCR7 as a potential anti-thrombotic strategy in platelet associated cardiovascular dis-orders, particularly in coronary artery disease (CAD) patients post-MI.

Influence of platelet count on the expression of platelet collagen receptor glycoprotein VI (GPVI) in patients with acute coronary syndrome

2009 ◽  
Vol 101 (05) ◽  
pp. 911-915 ◽  
Author(s):  
Boris Bigalke ◽  
Konstantinos Stellos ◽  
Dimitrios Stakos ◽  
Thomas Joos ◽  
Oliver Pötz ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Count ◽  
Thrombus Formation ◽  
Surface Expression ◽  
Platelet Surface ◽  
Glycoprotein Vi ◽  
Coronary Syndrome ◽  
Symptomatic Coronary Artery Disease ◽  
Artery Disease ◽  
Collagen Receptor

SummaryPlatelets play a key role in the development of an acute coronary syndrome (ACS) and contribute to cardiovascular events. Platelet collagen receptor glycoprotein VI (GPVI) contributes significantly to platelet adhesion and thrombus formation in ACS. We consecutively investigated both the platelet count and the platelet surface expression of GPVI in 843 patients with a symptomatic coronary artery disease verified by coronary angiography. Four hundred fourteen patients presented with stable angina pectoris and 429 patients with ACS. Platelet surface expression of GPVI and CD62P was determined by flow cytometry and platelet count with a coulter counter, plasmatic soluble GPVI was measured by ELISA. Platelet GPVI expression in patients with ACS was compared to platelet count. Patients with ACS showed significantly elevated GPVI expression levels in the first and second quartiles of platelet count compared to patients with higher platelet count [mean fluorescence intensity (MFI) ± standard deviation): 1st vs. 4th: 20.44 ± 6.1 vs. 18.62 ± 3.7; p=0.012; 2ndvs.3rd:21.2±8.5vs.18.76±3.7;P=0.03; 2ndvs.4th: 21.2±8.5vs.18.62±3.7;P=0.004], which was paralleled in trend for the CD62P expression [MFI: 1st vs. 4th: 11.2 ± 6.8 vs. 12.3 ± 9; p=0.057; 2nd vs. 3rd: 16.3 ± 16 vs.12.7 ± 5.3; p=0.138; 2nd vs. 4th: 16.3 ± 16 vs.11 ± 4.4; p=0.043]. In a subgroup of 48 patients with ACS, determination of soluble GPVI showed similar results [plasma GPVI (ng/ml): 1stvs.4th: 1.6 ± 0.6 vs. 1.2 ± 0.4; p=0.046; 1st vs. 3rd: 1.6 ± 0.6 vs. 1.1 ± 0.5; p=0.038; 2nd vs. 3rd: 1.9 ± 0.8 vs. 1.1 ± 0.5; p=0.04; 2nd vs. 4th: 1.9 ± 0.8 vs. 1.2 ± 0.4; p=0.056]. Thus, a lower platelet count comes along with a higher GPVI surface expression and plasma concentration in patients with ACS, which potentially reflects increased activation and enhanced recruitment of platelets to the site of vascular injury.

scholarly journals Sandwich Immunoassay for Soluble Glycoprotein VI in Patients with Symptomatic Coronary Artery Disease

2011 ◽  
Vol 57 (6) ◽  
pp. 898-904 ◽  
Author(s):  
Boris Bigalke ◽  
Oliver Pötz ◽  
Elisabeth Kremmer ◽  
Tobias Geisler ◽  
Peter Seizer ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Troponin I ◽  
Early Stage ◽  
Surface Expression ◽  
Sandwich Immunoassay ◽  
Platelet Glycoprotein ◽  
Glycoprotein Vi ◽  
Coronary Syndrome ◽  
St Elevation ◽  
Artery Disease

BACKGROUND Platelet glycoprotein VI (pGPVI) expression is increased in acute coronary syndrome (ACS), reflecting platelet activation. There is no reliable method available to measure pGPVI. Our aim was to develop a bead-based sandwich immunoassay to measure soluble GPVI (sGPVI). METHODS Based on antibodies for sGPVI developed earlier, we established and validated a bead-based sandwich immunoassay in 2438 consecutive patients with stable angina pectoris (SAP; n = 1371), non–ST-elevation myocardial infarction (NSTEMI; n = 724), and ST-elevation MI (STEMI; n = 343). In a subgroup (n = 1011), we measured surface expression of pGPVI using flow cytometry. RESULTS The assay revealed a working range of 8–500 ng/L. Intra- and interassay imprecision was <7% and <14%, respectively. Patients with NSTEMI and STEMI showed significantly lower mean sGPVI concentrations than patients with SAP [mean (SD), 8.4 (3.6) μg/L and 8.6 (4.1) μg/L vs 9.8 (4.8) μg/L; P = 0.002], whereas subgroup analysis revealed significantly enhanced pGPVI in NSTEMI (n = 276) and STEMI (n = 80) patients compared with SAP (n = 655) [mean fluorescence intensity (SD), 21.2 (8.1) and 19.8 (6.8) vs 18.5 (7.7); P = 0.002 and P = 0.018]. pGPVI and sGPVI were inversely correlated (r = −0.076; P = 0.023). Area under the ROC curve was 0.716, 95% CI 0.681–0.751, for sGPVI, distinguishing patients with SAP from those with ACS, and was superior (P = 0.044) to the curve of subgroup analysis for pGPVI (0.624, 95% CI 0.586–0.662). sGPVI (P = 0.023) and pGPVI (P = 0.028) had better association with the development of ACS than troponin I (P = 0.055) in the very early stage of disease, based on logistic regression analysis. CONCLUSIONS This sandwich immunoassay reliably measures sGPVI and may help to identify patients with ACS earlier than other laboratory markers.

Abstract 505: Circulating Monocyte-Platelet Aggregates are Different Across Phenotypes of Vascular Disease

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Nicole Allen ◽  
Yu Guo ◽  
Adriana Perez ◽  
Edna Bissoon ◽  
Matthew Cambria ◽  
...  
Keyword(s):  
Risk Factors ◽  
Linear Regression ◽  
Vascular Disease ◽  
Ex Vivo ◽  
Surface Expression ◽  
Platelet Activity ◽  
Platelet Surface ◽  
Vascular Bed ◽  
Platelet Aggregates ◽  
Artery Disease

Background: Platelets are a major culprit in the pathogenesis of cardiovascular disease (CVD). Although vascular disease in different arterial beds share common risk factors, the role of platelet activity may differ by vascular bed. Clinical trials suggest that more potent antiplatelet therapy is needed in lower extremity peripheral artery disease (PAD) than coronary artery disease (CAD). We investigated circulating monocyte platelet aggregates (MPA), a reproducible ex vivo measurement of platelet activity, in patients with CVD (PAD, CAD, carotid artery stenosis [CAS], and abdominal aortic aneurysm [AAA]) and disease controls. Methods: Subjects with CVD (n=351) and disease controls (n=73) had MPA measured using strict quality control, all of whom were on aspirin monotherapy. MPA were identified by CD14/CD61 positivity. Data is represented as median (IQR, interquartile range). Wilcoxon rank sum, Wilcoxon signed rank, and multivariable linear regression were used to analyze data. Results: Platelets aggregated with monocytes had a higher platelet surface expression of PAC-1, P-selectin, and CD40 versus platelets not aggregated with monocytes (P<0.05 for each comparison). Compared with controls, MPA was significantly higher in CVD (14.5 [10.3, 27.8] vs. 9.4 [8.2, 11.5], P<0.001) which remained significant after multivariable adjustment for demographics and risk factors (β=9.1 (SER=3.9), P=0.02). For each vascular disease phenotype, MPA was higher than controls ( Figure ). In a multivariable linear regression model including demographics, risk factors and each vascular bed, PAD was the only vascular disease associated with a higher value of MPA (β=10.2 (SER=2.4), P<0.001). Conclusions: Platelets aggregated with monocytes have increased platelet activity and are significantly elevated in subjects with PAD. Future studies understanding the platelet profile in PAD and its clinical relevance are needed.

scholarly journals Platelet surface expression of cyclophilin A is associated with increased mortality in patients with symptomatic coronary artery disease

2019 ◽  
Vol 18 (1) ◽  
pp. 234-242 ◽  
Author(s):  
Dominik Rath ◽  
Saskia Ungern‐Sternberg ◽  
David Heinzmann ◽  
Manuel Sigle ◽  
Mona Monzien ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cyclophilin A ◽  
Surface Expression ◽  
Platelet Surface ◽  
Symptomatic Coronary Artery Disease ◽  
Artery Disease

Platelets as a novel source of Gremlin-1: Implications for thromboinflammation

2017 ◽  
Vol 117 (02) ◽  
pp. 311-324 ◽  
Author(s):  
Madhumita Chatterjee ◽  
Alexander Behrendt ◽  
Martina Schmid ◽  
Sandra Beck ◽  
Martina Schneider ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Ex Vivo ◽  
Thrombus Formation ◽  
Surface Expression ◽  
Coronary Syndrome ◽  
Monocyte Migration ◽  
Artery Disease ◽  
Stable Cad ◽  
Induced Apoptosis ◽  
Gremlin 1

SummaryPlatelets mediating haemostasis-thrombosis are central players in coronary artery disease (CAD). We characterised platelets as a novel source of Gremlin-1. Platelets express Gremlin-1 like inflammatory and endothelial cells. Gremlin-1 co-localised with P-selectin containing randomly distributed α–granules under resting state, which were peripheralised following platelet activation or adhesion over fibrinogen-coated surface. Gremlin-1 release upon activation with ADP, CRP, and TRAP was detected as enhanced surface expression; also in activated platelet supernatant as detected by Western Blot following CRP activation and by ELISA upon activation with ADP, CRP, PAR-1, and PAR4 agonist. Recombinant (rh)Gremlin-1 synergistically enhanced CRP-triggered intracellular calcium mobilisation, ADP-TRAP induced platelet activation, aggregation, and thrombin-activation triggered apoptosis; also thrombus formation ex vivo. Intracellular localisation of macrophage migration inhibitory factor (MIF) and Gremlin-1 a high-affinity binding partner and functional antagonist of MIF were found in intracoronary thrombus sections from acute coronary syndrome (ACS) patients and showed moderate overlap in α-granules of platelets. Intra-platelet Gremlin-1 levels were significantly decreased in ACS patients as compared to stable CAD (n=235). rhGremlin-1 also counteracted the anti-apoptotic and anti-thrombotic effects of rhMIF on platelets. Platelet-derived-Gremlin-1 prompted monocyte migration, facilitated adhesion under static and dynamic arterial flow conditions to collagen-adherent activated platelets; supported monocyte survival against BH-3-mimetic–induced apoptosis and macrophage differentiation in monocyte-platelet co-culture system, which were counteracted upon Gremlin-1 neutralisation. Thus platelet derived Gremlin-1 might contribute to the elevated circulating levels of Gremlin-1 in ACS and serve as a thrombo-inflammatory mediator in cardiovascular pathophysiologies.

Study on Vitamin D deficiency in patients of diabetes mellitus presenting with Acute Coronary syndrome in a tertiary care hospital in South India

2020 ◽  
Vol 11 (5) ◽  
pp. 49-53
Author(s):  
Archana Bhat ◽  
Arunachalam Ramachandran ◽  
Pradeep Periera ◽  
Akshatha Rao Aroor
Keyword(s):  
Diabetes Mellitus ◽  
Coronary Artery Disease ◽  
Vitamin D ◽  
Acute Coronary Syndrome ◽  
Coronary Artery ◽  
Vitamin D Deficiency ◽  
Coronary Syndrome ◽  
Vitamin D Levels ◽  
Luminal Stenosis ◽  
Artery Disease

Background: Vitamin D, a fat-soluble vitamin has its receptor present in myriad of tissues and it modulates multiple cellular processes. Vitamin D deficiency is reported to be associated with coronary artery disease. Cardiovascular disease is the leading cause of mortality worldwide. Aims and Objective: The primary outcome was to investigate if there is a correlation of 25-OH levels with the percentage of luminal stenosis, as measured with coronary angiogram. The secondary outcome was to determine the differences in angiographically proven luminal stenosis across categories of 25-OH vitamin D levels. Materials and Methods: Thirty patients with acute coronary syndrome with diabetes mellitus were included in this cross-sectional descriptive study. All patients were tested for fasting vitamin D levels, fasting blood sugar, HbA1C and serum creatinine. Detailed history of the patients was recorded. Data was analyzed by the statistical software SPSS version 19 and p value <0.05 was considered significant. Statistical tests like Chi- square, independent t test and log regression was used. Results: In this study 30 patients undergoing coronary angiography for acute coronary syndrome, Vitamin D levels showed severe deficiency in 6.7% (2) cases while mild deficiency was seen in 50% of the cases. Patients with single vessel disease on the coronary angiogram had lower mean HbA1C (9.18) levels in our study. Patients with triple vessel disease had poorly controlled mean HbA1C levels (10.42). Conclusion: In this study we did not find any significant difference between the serum Vitamin D deficiency levels with patients with angiographic severity of the coronary artery disease. Patients with poorly controlled diabetes mellitus had more severe angiographic proven coronary artery disease.

Atypical Takotsubo Cardiomyopathy with Hypokinetic Left Mid-ventricle and Apical Wall Sparing: A Case Report and Literature Review

2020 ◽  
Vol 16 (3) ◽  
pp. 241-246
Author(s):  
Dipesh Ludhwani ◽  
Belaal Sheikh ◽  
Vasu K Patel ◽  
Khushali Jhaveri ◽  
Mohammad Kizilbash ◽  
...  
Keyword(s):  
Case Report ◽  
Takotsubo Cardiomyopathy ◽  
Systolic Dysfunction ◽  
Obstructive Coronary Artery Disease ◽  
Left Ventricular ◽  
Reduced Ejection Fraction ◽  
Coronary Syndrome ◽  
Normal Left Ventricular ◽  
Artery Disease

Background: Takotsubo Cardiomyopathy (TTC) is an uncommon cause of acute reversible ventricular systolic dysfunction in the absence of obstructive Coronary Artery Disease (CAD). Typically manifesting as apical wall ballooning, TTC can rarely present atypically with apical wall sparing. Case report: A 62-year-old female presented with complaints of chest pain and features mimicking acute coronary syndrome. Coronary angiogram revealed no obstructive CAD and left ventriculogram showed reduced ejection fraction, normal left ventricular apex and hypokinetic mid-ventricles consistent with atypical TTC. The patient was discharged home on heart failure medications and a follow-up transthoracic echocardiogram demonstrated improved left ventricular function with no wall motion abnormality. Conclusion: This case report provides an insight into the diagnosis and management of TTC in the absence of pathognomic features.

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