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.

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.

Diagnostic work-up and therapeutic implications in MINOCA: need for a personalized approach

2021 ◽  
Vol 17 (1) ◽  
pp. 149-154 ◽  
Author(s):  
Marco Giuseppe Del Buono ◽  
Rocco Antonio Montone ◽  
Giulia Iannaccone ◽  
Maria Chiara Meucci ◽  
Riccardo Rinaldi ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Obstructive Coronary Artery Disease ◽  
Benign Condition ◽  
Therapeutic Implications ◽  
Risk Of Mortality ◽  
Artery Disease ◽  
Personalized Approach ◽  
Diagnostic Work ◽  
Work Up

Myocardial infarction with non-obstructive coronary artery (MINOCA) disease represents a heterogeneous clinical conundrum accounting for about 6% of all acute myocardial infarction (MI) cases. Initially believed to be a benign condition, is now becoming clear that MINOCA is associated with a non-negligible risk of mortality, rehospitalization, disability and angina burden at follow-up, with high socioeconomic costs. To date, there are no prospective clinical trials in this population and cannot be assumed that benefits observed in patients suffering from MI with obstructive coronary artery disease may successfully translate to this syndrome. Herein, we comment on the importance of the multimodality assessment to properly identify and treat the specific causes of MINOCA, in order to improve prognosis and the quality of life in these patients.

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.

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.

CASE SERIES OF PREGNANCY-ASSOCIATED MYOCARDIAL INFARCTION: AN EPIDEMIC IN WAITING

2021 ◽  
pp. 28-30
Author(s):  
Shree Bharathi ◽  
Sasirekha Rengaraj
Keyword(s):  
Myocardial Infarction ◽  
Care Center ◽  
Tertiary Care ◽  
Case Series ◽  
Fetal Outcome ◽  
Therapeutic Implications ◽  
Threatening Condition ◽  
Life Threatening ◽  
Common Etiology ◽  
Artery Disease

Acute myocardial infarction during pregnancy or postpartum period is a rare but life-threatening condition associated with poor maternal and fetal outcome. Although atherosclerotic coronary artery disease is the most common etiology in general population, the causation is more diverse in pregnancy and this may have therapeutic implications. Early diagnosis and timely management with collaboration among Maternal-fetal medicine specialist, interventional cardiologist, cardiac anaesthetist, intensivist and neonatologist is essential to prevent maternal cardiac deaths. We present a case series of two patients with postpartum and antepartum acute MI, respectively and their diagnosis, management and outcomes in a tertiary care center.

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

scholarly journals MicroRNAs in Acute ST Elevation Myocardial Infarction—A New Tool for Diagnosis and Prognosis: Therapeutic Implications

2021 ◽  
Vol 22 (9) ◽  
pp. 4799
Author(s):  
Alina Ioana Scărlătescu ◽  
Miruna Mihaela Micheu ◽  
Nicoleta-Monica Popa-Fotea ◽  
Maria Dorobanțu
Keyword(s):  
Myocardial Infarction ◽  
Therapeutic Targets ◽  
St Elevation Myocardial Infarction ◽  
Cardiac Damage ◽  
Therapeutic Implications ◽  
Diagnosis And Prognosis ◽  
Coronary Syndromes ◽  
St Elevation ◽  
Artery Disease ◽  
Circulating Levels

Despite diagnostic and therapeutic advances, coronary artery disease and especially its extreme manifestation, ST elevation myocardial infarction (STEMI), remain the leading causes of morbidity and mortality worldwide. Early and prompt diagnosis is of great importance regarding the prognosis of STEMI patients. In recent years, microRNAs (miRNAs) have emerged as promising tools involved in many pathophysiological processes in various fields, including cardiovascular diseases. In acute coronary syndromes (ACS), circulating levels of miRNAs are significantly elevated, as an indicator of cardiac damage, making them a promising marker for early diagnosis of myocardial infarction. They also have prognostic value and great potential as therapeutic targets considering their key function in gene regulation. This review aims to summarize current information about miRNAs and their role as diagnostic, prognostic and therapeutic targets in STEMI patients.

A Cost-effectiveness Analysis of Aspirin versus Oral Anticoagulants after Acute Myocardial Infarction in Italy

1998 ◽  
Vol 80 (12) ◽  
pp. 887-893 ◽  
Author(s):  
Jacopo Gianetti ◽  
Gianfranco Gensini ◽  
Raffaele De Caterina
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Cost Effectiveness ◽  
Interventional Procedures ◽  
Cost Allocation ◽  
Oral Anticoagulants ◽  
The United States ◽  
Cost Effectiveness Analysis ◽  
Effectiveness Analysis ◽  
Artery Disease

SummaryAims. The recent publication of two large trials of secondary prevention of coronary artery disease with oral anticoagulants (WARIS and ASPECT) has caused a revival of the interest for this antithrombotic therapy in a clinical setting where the use of aspirin is common medical practice. Despite this, the preferential use of aspirin has been supported by an American cost-effectiveness analysis (JAMA 1995; 273: 965). Methods and Results. Using the same parameters used in that analysis and incidence of events from the Antiplatelet Trialists Collaboration and the ASPECT study, we re-evaluated the economic odds in favor of aspirin or oral anticoagulants in the Italian Health System, which differs significantly in cost allocation from the United States system and is, conversely, similar to other European settings. Recalculated costs associated with each therapy were 2,150 ECU/ patient/year for oral anticoagulants and 2,187 ECU/patient/year for aspirin. In our analysis, the higher costs of oral anticoagulants versus aspirin due to a moderate excess of bleeding (about 10 ECU/ patient/year) and the monitoring of therapy (168 ECU/ patient/year) are more than offset by an alleged savings for recurrent ischemic syndromes and interventional procedures (249 ECU/ patient/year). Conclusions. Preference of aspirin vs. oral anticoagulants in a pharmaco-economical perspective is highly dependent on the geographical situation whereupon calculations are based. On a pure cost-effectiveness basis, and in the absence of data of direct comparisons between aspirin alone versus I.N.R.-adjusted oral anticoagulants, the latter are not more expensive than aspirin in Italy and, by cost comparisons, in other European countries in the setting of post-myocardial infarction.

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