Role for Thrombin Receptor Antagonism With Vorapaxar in Secondary Prevention of Atherothrombotic Events: From Bench to Bedside

Moon, Jae Youn; Franchi, Francesco; Rollini, Fabiana; Angiolillo, Dominick J.

doi:10.1177/1074248417708617

Cited by 18 publications

(16 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cardiovasc Diagn Ther 2018;8(5):594-609 cdt.amegroups.com (129)(130)(131). However, of these only vorapaxar, a PAR-1 receptor inhibitor, has been approved for clinical use.…”

Section: New Therapeutic Agentsmentioning

confidence: 99%

Diabetes and antiplatelet therapy: from bench to bedside

Rios

Franchi

Rollini

et al. 2018

Cardiovasc. Diagn. Ther

Self Cite

View full text Add to dashboard Cite

Diabetes mellitus (DM) is a metabolic disorder associated with accelerated atherogenesis and an increased risk of atherothrombotic complications. Multiple mechanisms contribute to the prothrombotic status which characterizes DM patients underscoring the importance of antiplatelet therapies used for secondary prevention in these patients. For many years, dual antiplatelet therapy (DAPT) with aspirin and the P2Y 12 inhibitor clopidogrel has represented the mainstay of treatment following an acute coronary syndrome (ACS) or in patients undergoing percutaneous coronary interventions (PCI). Although DAPT reduces the incidence of atherothrombotic recurrences, these rates remain high in DM patients underscoring the need for more efficacious therapies. Oral platelet P2Y 12 receptor inhibitors with enhanced potency, such as prasugrel and ticagrelor, as well as antiplatelet therapies such as vorapaxar inhibiting the thrombin-mediated platelet signaling pathway, constitute treatment opportunities for patients with DM and have shown to be associated with a greater reduction in ischemic recurrences, albeit at the cost of more bleeding. This article reviews currently available antiplatelet agents and delivers an update on the advances and drawbacks of these agents used for secondary prevention in DM patients experiencing an ACS or undergoing PCI.

show abstract

“…Cardiovasc Diagn Ther 2018;8(5):594-609 cdt.amegroups.com (129)(130)(131). However, of these only vorapaxar, a PAR-1 receptor inhibitor, has been approved for clinical use.…”

Section: New Therapeutic Agentsmentioning

confidence: 99%

Diabetes and antiplatelet therapy: from bench to bedside

Rios

Franchi

Rollini

et al. 2018

Cardiovasc. Diagn. Ther

Self Cite

View full text Add to dashboard Cite

show abstract

“…PAR-1 enhances cancer cell invasiveness via increasing adhesion to extracellular matrix. After thrombin/PAR-1 stimulation, several cancer cell lines demonstrated increased platelets adhesion as well as to aorta and capillaries [ 32 – 34 , 45 , 49 – 50 ]. Prothrombin-induced HIF-1α increases mRNA expression of torsion, whose protein level is also mediated by activated PAR-1: all these can enhance EMT and increase tumor metastasis [ 42 ].…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, the use of anti-α v b 5 antibodies specifically attenuated PAR-1-imediated invasion[ 50 ]. PAR-1 signaling induced expression of integrin IIb3 and P-selectin promoted melanoma cell-EC/platelet interaction, thereby increasing the metastatic potential of cancer cells [ 33 – 34 , 45 , 52 – 53 ]. Overexpression of NF-κB, EGFR can activate PAR-1 signaling, which consequently promotes tumor cell growth and invasion [ 54 ].…”

Section: Introductionmentioning

confidence: 99%

Protease-activated receptor-1 (PAR-1): a promising molecular target for cancer

Liu

Song

et al. 2017

Oncotarget

View full text Add to dashboard Cite

PAR-1 is expressed not only in epithelium, neurons, astrocytes, immune cells, but also in cancer-associated fibroblasts, ECs (epithelial cells), myocytes of blood vessels, mast cells, and macrophages in tumor microenvironment, whereas PAR-1 stimulates macrophages to synthesize and secrete thrombin as well as other growth factors, resulting in enhanced cell proliferation, tumor growth and metastasis. Therefore, considerable effort has been devoted to the development of inhibitors targeting PAR-1. Here, we provide a comprehensive review of PAR-1’s role in cancer invasiveness and dissemination, as well as potential therapeutic strategies targeting PAR-1 signaling.

show abstract

“…Direct inhibitors of PAR-1 have been developed and are available in the clinic as antiplatelet drugs for secondary prevention of myocardial infarction, ischemic stroke, and peripheral artery disease (Tricoci, 2012;Bonaca, 2014;Magnani, 2015;Ungar, 2018). The antiaggregant effect is achieved through inhibition of the thrombi-receptor (PAR-1) expressed on the membrane of platelets (Moon, 2018). Vorapaxar has been available for more than 6 years, and the results obtained in atherothrombotic diseases were rather modest in terms of reduction of new acute ischemic events, and the drugs increases the risk of bleeding and hemorrhagic stroke (Sharma, 2017).…”

Section: Coagulation Factor Proteases and Pars In Afmentioning

confidence: 99%

Pharmacological Inhibition of Serine Proteases to Reduce Cardiac Inflammation and Fibrosis in Atrial Fibrillation

et al. 2019

View full text Add to dashboard Cite

Systemic inflammation correlates with an increased risk of atrial fibrillation (AF) and thrombogenesis. Systemic inflammation alters vessel permeability, allowing inflammatory and immune cell migration toward target organs, including the heart. Among inflammatory cells infiltrating the atria, macrophages and mast cell have recently attracted the interest of basic researchers due to the pathogenic mechanisms triggered by their activation. This chemotactic invasion is likely implicated in shortand long-term changes in cardiac cell-to-cell communication and in triggering fibrous tissue accumulation in the atrial myocardium and electrophysiological rearrangements of atrial cardiomyocytes, thus favoring the onset and progression of AF. Serine proteases are a large and heterogeneous class of proteases involved in several processes that are important for cardiac function and are involved in cardiac diseases, such as (i) coagulation, (ii) fibrinolysis, (iii) extracellular matrix degradation, (iv) activation of receptors (i.e., protease-activated receptors [PPARs]), and (v) modulation of the activity of endogenous signals. The recognition of serine proteases substrates and their involvement in inflammatory/profibrotic mechanisms allowed the identification of novel cardio-protective mechanisms for commonly used drugs that inhibit serine proteases. The aim of this review is to summarize knowledge on the role of inflammation and fibrosis as determinants of AF. Moreover, we will recapitulate current findings on the role of serine proteases in the pathogenesis of AF and the possible beneficial effects of drugs inhibiting serine proteases in reducing the risk of AF through decrease of cardiac inflammation and fibrosis. These drugs include thrombin and factor Xa inhibitors (used as oral anticoagulants), dipeptidyl-peptidase 4 (DPP4) inhibitors, used for type-2 diabetes, as well as novel experimental inhibitors of mast cell chymases.

show abstract

Role for Thrombin Receptor Antagonism With Vorapaxar in Secondary Prevention of Atherothrombotic Events: From Bench to Bedside

Cited by 18 publications

References 85 publications

Diabetes and antiplatelet therapy: from bench to bedside

Diabetes and antiplatelet therapy: from bench to bedside

Protease-activated receptor-1 (PAR-1): a promising molecular target for cancer

Pharmacological Inhibition of Serine Proteases to Reduce Cardiac Inflammation and Fibrosis in Atrial Fibrillation

Contact Info

Product

Resources

About