scholarly journals Epigallocatechin gallate inhibits release of extracellular vesicles from platelets without inhibiting phosphatidylserine exposure

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sarah L. Millington-Burgess ◽  
Matthew T. Harper
Keyword(s):  
Myocardial Infarction ◽  
Cause Of Death ◽  
Extracellular Vesicles ◽  
Therapeutic Target ◽  
Arterial Thrombosis ◽  
Epigallocatechin Gallate ◽  
Annexin V ◽  
Phospholipid Scramblase ◽  
Activated Platelets ◽  
Phosphatidylserine Exposure

AbstractArterial thrombosis triggers myocardial infarction and is a leading cause of death worldwide. Procoagulant platelets, a subpopulation of activated platelets that expose phosphatidylserine (PS), promote coagulation and occlusive thrombosis. Procoagulant platelets may therefore be a therapeutic target. PS exposure in procoagulant platelets requires TMEM16F, a phospholipid scramblase. Epigallocatechin gallate (EGCG) has been reported to inhibit TMEM16F but this has been challenged. We investigated whether EGCG inhibits PS exposure in procoagulant platelets. PS exposure is often measured using fluorophore-conjugated annexin V. EGCG quenched annexin V-FITC fluorescence, which gives the appearance of inhibition of PS exposure. However, EGCG did not quench annexin V-APC fluorescence. Using this fluorophore, we show that EGCG does not inhibit annexin V binding to procoagulant platelets. We confirmed this by using NBD-labelled PS to monitor PS scrambling. EGCG did not quench NBD fluorescence and did not inhibit PS scrambling. Procoagulant platelets also release PS-exposing extracellular vesicles (EVs) that further propagate coagulation. Surprisingly, EGCG inhibited EV release. This inhibition required the gallate group of EGCG. In conclusion, EGCG does not inhibit PS exposure in procoagulant platelets but does inhibit the EV release. Future investigation of this inhibition may help us further understand how EVs are released by procoagulant platelets.

scholarly journals Evidence that polyphenols do not inhibit the phospholipid scramblase TMEM16F

2020 ◽  
Vol 295 (35) ◽  
pp. 12537-12544
Author(s):  
Trieu Le ◽  
Son C. Le ◽  
Yang Zhang ◽  
Pengfei Liang ◽  
Huanghe Yang
Keyword(s):  
Skeletal Development ◽  
Epigallocatechin Gallate ◽  
Annexin V ◽  
Membrane Transporters ◽  
Flip Flop ◽  
Positive Effects ◽  
Phospholipid Scramblase ◽  
Dual Functional ◽  
Health And Disease ◽  
Phospholipid Scrambling

TMEM16 Ca2+-activated phospholipid scramblases (CaPLSases) mediate rapid transmembrane phospholipid flip-flop and as such play essential roles in various physiological and pathological processes such as blood coagulation, skeletal development, viral infection, cell-cell fusion, and ataxia. Pharmacological tools specifically targeting TMEM16 CaPLSases are urgently needed to understand these novel membrane transporters and their contributions to health and disease. Tannic acid (TA) and epigallocatechin gallate (EGCG) were recently reported as promising TMEM16F CaPLSase inhibitors. However, our present study shows that TA and EGCG do not inhibit the phospholipid-scrambling or ion conduction activities of the dual-functional TMEM16F. Instead, we found that TA and EGCG mainly acted as fluorescence quenchers that rapidly suppress the fluorophores conjugated to annexin V, a phosphatidylserine-binding probe commonly used to report on TMEM16 CaPLSase activity. These data demonstrate the false positive effects of TA and EGCG on inhibiting TMEM16F phospholipid scrambling and discourage the use of these polyphenols as CaPLSase inhibitors. Appropriate controls as well as a combination of both fluorescence imaging and electrophysiological validation are necessary in future endeavors to develop TMEM16 CaPLSase inhibitors.

scholarly journals Extracellular Vesicles Are Associated With Outcome in Veno-Arterial Extracorporeal Membrane Oxygenation and Myocardial Infarction

2021 ◽  
Vol 8 ◽  
Author(s):  
Patrick M. Siegel ◽  
Ileana Bender ◽  
Julia Chalupsky ◽  
Lukas A. Heger ◽  
Marina Rieder ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
At Risk ◽  
Inflammatory Response ◽  
Extracorporeal Membrane Oxygenation ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Extracellular Vesicles ◽  
Annexin V ◽  
Left Ventricular ◽  
Va Ecmo

Background: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is being increasingly applied in patients with circulatory failure, but mortality remains high. An inflammatory response syndrome initiated by activation of blood components in the extracorporeal circuit may be an important contributing factor. Patients with ST-elevation myocardial infarction (STEMI) may also experience a systemic inflammatory response syndrome and are at risk of developing cardiogenic shock and cardiac arrest, both indications for VA-ECMO. Extracellular vesicles (EV) are released by activated cells as mediators of intercellular communication and may serve as prognostic biomarkers. Cardiomyocyte EV, released upon myocardial ischemia, hold strong potential for this purpose. The aim of this study was to assess the EV-profile in VA-ECMO and STEMI patients and the association with outcome.Methods: In this prospective observational study, blood was sampled on day 1 after VA-ECMO initiation or myocardial reperfusion (STEMI patients). EV were isolated by differential centrifugation. Leukocyte, platelet, endothelial, erythrocyte and cardiomyocyte (caveolin-3+) Annexin V+ EV were identified by flow cytometry. EV were assessed in survivors vs. non-survivors of VA-ECMO and in STEMI patients with normal-lightly vs. moderately-severely reduced left ventricular function. Logistic regression was conducted to determine the predictive accuracy of EV. Pearson correlation analysis of EV with clinical parameters was performed.Results: Eighteen VA-ECMO and 19 STEMI patients were recruited. Total Annexin V+, cardiomyocyte and erythrocyte EV concentrations were lower (p ≤ 0.005) while the percentage of platelet EV was increased in VA-ECMO compared to STEMI patients (p = 0.002). Total Annexin V+ EV were increased in non-survivors of VA-ECMO (p = 0.01), and higher levels were predictive of mortality (AUC = 0.79, p = 0.05). Cardiomyocyte EV were increased in STEMI patients with moderately-severely reduced left ventricular function (p = 0.03), correlated with CK-MBmax (r = 0.57, p = 0.02) and time from reperfusion to blood sampling (r = 0.58, p = 0.01). Leukocyte EV correlated with the number of coronary stents placed (r = 0.60, p = 0.02).Conclusions: Elevated total Annexin V+ EV on day 1 of VA-ECMO are predictive of mortality. Increased cardiomyocyte EV on day 1 after STEMI correlate with infarct size and are associated with poor outcome. These EV may aid in the early identification of patients at risk of poor outcome, helping to guide clinical management.

scholarly journals A case report of multisite arterial thrombosis in a patient with coronavirus disease 2019 (COVID-19)

2020 ◽  
Author(s):  
Marco Angelillis ◽  
Marco De Carlo ◽  
Andrea Christou ◽  
Michele Marconi ◽  
Davide M Mocellin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Case Report ◽  
Arterial Thrombosis ◽  
Leg Pain ◽  
Nasopharyngeal Swab ◽  
Limb Ischaemia ◽  
Total Occlusion ◽  
Left Common Iliac Artery ◽  
Acute Limb Ischaemia ◽  
The Right

Abstract Background A systemic coagulation dysfunction has been associated with COVID-19. In this case report, we describe a COVID-19-positive patient with multisite arterial thrombosis, presenting with acute limb ischaemia and concomitant ST-elevation myocardial infarction and oligo-symptomatic lung disease. Case summary An 83-year-old lady with history of hypertension and chronic kidney disease presented to the Emergency Department with acute-onset left leg pain, pulselessness, and partial loss of motor function. Acute limb ischaemia was diagnosed. At the same time, a routine ECG showed ST-segment elevation, diagnostic for inferior myocardial infarction. On admission, a nasopharyngeal swab was performed to assess the presence of SARS-CoV-2, as per hospital protocol during the current COVID-19 pandemic. A total-body CT angiography was performed to investigate the cause of acute limb ischaemia and to rule out aortic dissection; the examination showed a total occlusion of the left common iliac artery and a non-obstructive thrombosis of a subsegmental pulmonary artery branch in the right basal lobe. Lung CT scan confirmed a typical pattern of interstitial COVID-19 pneumonia. Coronary angiography showed a thrombotic occlusion of the proximal segment of the right coronary artery. Percutaneous coronary intervention was performed, with manual thrombectomy, followed by deployment of two stents. The patient was subsequently transferred to the operating room, where a Fogarty thrombectomy was performed. The patient was then admitted to the COVID area of our hospital. Seven hours later, the swab returned positive for COVID-19. Discussion COVID-19 can have an atypical presentation with thrombosis at multiple sites.

Injection‐Free Delivery of MSC‐Derived Extracellular Vesicles for Myocardial Infarction Therapeutics

2021 ◽  
pp. 2100312
Author(s):  
Junnan Tang ◽  
Xiaolin Cui ◽  
Zenglei Zhang ◽  
Yanyan Xu ◽  
Jiacheng Guo ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Extracellular Vesicles

scholarly journals JDP2, a Novel Molecular Key in Heart Failure and Atrial Fibrillation?

2021 ◽  
Vol 22 (8) ◽  
pp. 4110
Author(s):  
Gerhild Euler ◽  
Jens Kockskämper ◽  
Rainer Schulz ◽  
Mariana S. Parahuleva
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Atrial Fibrillation ◽  
Cardiac Dysfunction ◽  
Therapeutic Target ◽  
Close Correlation ◽  
Disease Development ◽  
Major Life ◽  
Life Threatening ◽  
Current Therapies

Heart failure (HF) and atrial fibrillation (AF) are two major life-threatening diseases worldwide. Causes and mechanisms are incompletely understood, yet current therapies are unable to stop disease progression. In this review, we focus on the contribution of the transcriptional modulator, Jun dimerization protein 2 (JDP2), and on HF and AF development. In recent years, JDP2 has been identified as a potential prognostic marker for HF development after myocardial infarction. This close correlation to the disease development suggests that JDP2 may be involved in initiation and progression of HF as well as in cardiac dysfunction. Although no studies have been done in humans yet, studies on genetically modified mice impressively show involvement of JDP2 in HF and AF, making it an interesting therapeutic target.

Heparin Neutralizing Activity in the Diagnosis of Acute Myocardial Infarction

1975 ◽  
Author(s):  
J. R. O’Brien ◽  
M. D. Etherington ◽  
S. Jamieson ◽  
J. Sussex
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Chest Pain ◽  
Acute Chest Pain ◽  
Platelet Factor 4 ◽  
Clotting Time ◽  
Platelet Factor ◽  
Neutralizing Activity ◽  
Platelet Poor Plasma ◽  
Activated Platelets

We have previously demonstrated that, relative to controls, patients long after myocardial infarction and patients with atherosclerosis have highly significantly shorter heparin thrombin clotting times (HTCT) using platelet poor plasma; but there was considerable overlap between the two groups.We have now studied 89 patients admitted with acute chest pain. In 54 of these a firm diagnosis of acute myocardial infarction (ac-MI) was made and the HTCT was very short (mean 12.8 sees) and in 48 it was less than 16 sees. In 34 patients, ac-MI was excluded and the diagnosis was usually “angina”; the HTCT was much longer (mean 25.1 sees) and in 32 it was over 16 sees. Thus there was almost no overlap between these two groups. It is suggested that this test should be adopted as a quick and reliable further test to establish a diagnosis of ac-MI (providing other reasons for very short HTCTs can be excluded, e.g. D. I. C., and provinding the patient’s thrombin clotting time is normal).This HTCT measures non-specific heparin neutralizing activity; nevertheless the evidence suggests that it is measuring platelet factor 4 liberated from damaged or “activated” platelets into the plasma. These findings underline the probable important contribution of platelets in ac-MI.

Sign in / Sign up

Export Citation Format

Share Document