Novel antiplatelet targets in the treatment of acute coronary syndromes

Alenazy, Fawaz O.; Thomas, Mark R.

doi:10.1080/09537104.2020.1763731

Cited by 19 publications

(28 citation statements)

References 134 publications

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“…Finally, we tried to examine the specific mechanisms of miR-497-5p in ACS. The pathologic process of ACS is complex and includes the rupture of atherosclerotic plaques, platelet aggregation during thrombosis leading to complete or partial coronary artery occlusion, and a series of inflammatory reactions at plaque and thrombus sites leading to myocardial ischemia and necrosis [ 36 ]. Increased secretion of TNF-α and IL-1β in the inflammatory state activates the increase of endothelial adhesion factor.…”

Section: Discussionmentioning

confidence: 99%

Serum miR-497-5p serves as a diagnostic biomarker for acute coronary syndrome and predicts the occurrence of major adverse cardiovascular events after percutaneous coronary intervention

et al. 2022

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This study aimed to investigate the diagnostic value of microRNA (miR)-497-5p in acute coronary syndrome (ACS) and its predictive value for the occurrence of adverse major adverse cardiovascular events (MACEs). Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to detect the expression of serum miR-497-5p in 110 ACS patients and 82 controls. And miR-497-5p levels were found to be significantly elevated in the patients (P < 0.001). Pearson correlation coefficient confirmed that miR-497-5p was positively correlated with Gensini scores (r = 0.684). The area under the Receiver-operating characteristic (ROC) curve was 0.861, which significantly identified patients with ACS, and was confirmed by logistic regression (OR = 8.533, 95%CI = 4.113–17.787, P < 0.001). Kaplan-Meier and Cox regression was performed to evaluate the predictive value of miR-497-5p in the occurrence of MACEs during a 6-month follow-up after percutaneous coronary intervention (PCI) in patients with ACS. The results demonstrated that miR-497-5p was an independent predictor of MACEs (HR = 4.773, 95%CI = 1.569–12.036, P = 0.013) and that patients with high level of miR-497-5p were more likely to develop MACEs after PCI (long-rank P = 0.019). Finally, miR-497-5p positively correlated with endothelial proinflammatory and adhesion factors. Our study suggests that serum miR-497-5p is a potential diagnostic marker for ACS and its elevated levels can predict a high risk of MACEs in ACS patients after PCI. And this may be associated with vascular endothelial injury.

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Section: Discussionmentioning

confidence: 99%

Serum miR-497-5p serves as a diagnostic biomarker for acute coronary syndrome and predicts the occurrence of major adverse cardiovascular events after percutaneous coronary intervention

et al. 2022

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“…After vacuum evaporation, the residue was dissolved in ethyl acetate and anhydrous ether and evaporated to remove hydrogen chloride three times to provide 0.28 g of yellow powder. The powder was purified with a reverse-phase C 18…”

Section: Synthesis Of 3s-thc-3-methyl Aspartyl Ester (Thcma)mentioning

confidence: 99%

“…The first two types are considered inadequate to fulfill daily or long-term therapeutic needs. For example, crizanlizumab, the first FDA-approved P-selectin inhibitor for sickle-cell treatment, 18 has the limitations of high manufacturing costs, short shelf life, and intravenous administration. Similarly, GSnP-6 also needs administration through the jugular cannula.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticles of a New Small-Molecule P-Selectin Inhibitor Attenuate Thrombosis, Inflammation, and Tumor Growth in Two Animal Models

Feng¹,

Wang²,

Muhtar³

et al. 2021

IJN

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Purpose: To assess whether the newly designed small-molecule oral P-selectin inhibitor 3S-1,2,3,4-tetrahydro-β-carboline-3-methyl aspartyl ester (THCMA) as a nanomedicine enhances antithrombosis, anti-inflammation, and antitumor activity more than the clinical trial drug PSI-697. Methods: THCMA was designed as an amphiphile containing pharmacophores of PSI-697. Its nanofeatures were explored with TEM, SEM, Tyndall effect, ζ-potential, FT-ICR-MS, and NOESY 2D 1 H NMR. The P-selectin inhibitory effect of THCMA was demonstrated with molecular docking, ultraviolet (UV) spectra, and competitive ELISA. In vivo and in vitro assays -anti-arterial thrombosis, anti-venous thrombosis, anti-inflammation, antitumor growth, anti-platelet aggregation, rat-tail bleeding time, anticoagulation index, soluble P-selectin (sP-selectin) expression, and serum TNFα expression -were performed to explore bioactivity and potential mechanisms. Water solubility of THCMA was measured using UV-absorption spectra. Results: THCMA self-assembled into nanorings of approximately 100 nm in diameter. Its water solubility was about 1,030-fold that of PSI-697. THCMA exhibited more potent P-selectin inhibitory effect than PSI-697. The oral efficacy of THCMA was 100-fold that of PSI-697 in inhibiting arterial and venous thrombosis and tenfold in inhibiting inflammation. THCMA inhibited thrombosis at a dose that produces no coagulation disorders and no bleeding risk. THCMA exhibited enhanced antitumor activity over PSI-697 without systemic chemotherapy toxicity. THCMA significantly inhibited platelet aggregation in vitro and downregulated the expression levels of serum sP-selectin and TNFα in vivo. Conclusion:A new small-molecule P-selectin inhibitor, THCMA, has been successfully designed as a nanomedicine with largely enhanced oral efficacy compared to the clinical trial drug PSI-697, and thus might be developed for the oral treatment of arterial thrombosis, venous thrombosis, inflammation, and cancer-associated thrombosis.

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“…Therefore, the development of novel antiplatelet agents with potent antithrombotic effects, but less impact on hemostasis, offers an appealing approach to reducing overall mortality. To this end, Fawaz Alenazy and Mark Thomas describe several promising novel antiplatelet drugs (including inhibitors of platelet GPVI, PAR4 and P-selectin, amongst others) that are currently under investigation in early-phase clinical trials [5]. In total, this review comprehensively summarises 11 antiplatelet agents currently undergoing clinical studies as well as many more not far behind at the animal model or in-vitro stage.…”

Section: Inhibiting Novel Mechanisms Of Thrombosis: Next-generation Amentioning

confidence: 99%

Inhibiting novel mechanisms of thrombosis: next-generation antiplatelet therapy

Thomas

Nicolson

2020

Platelets

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Novel antiplatelet targets in the treatment of acute coronary syndromes

Cited by 19 publications

References 134 publications

Serum miR-497-5p serves as a diagnostic biomarker for acute coronary syndrome and predicts the occurrence of major adverse cardiovascular events after percutaneous coronary intervention

Serum miR-497-5p serves as a diagnostic biomarker for acute coronary syndrome and predicts the occurrence of major adverse cardiovascular events after percutaneous coronary intervention

Nanoparticles of a New Small-Molecule P-Selectin Inhibitor Attenuate Thrombosis, Inflammation, and Tumor Growth in Two Animal Models

Inhibiting novel mechanisms of thrombosis: next-generation antiplatelet therapy

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