Abstract

Thrombosis remains a prime reason of mortality worldwide. With the available antithrombotic drugs, bleeding remains the major downside of current treatments. This raises a clinical concern for all patients undergoing antithrombotic therapy. Novel antithrombotics from marine sources offer a promising therapeutic alternative to this pathology. However, for any potential new molecule to be introduced as a real alternative to existing drugs, the exhibition of comparable anticoagulant potential with minimal off-target effects must be achieved. The relevance of marine antithrombotics, particularly sulfated polysaccharides, is largely due to their unique mechanisms of action and lack of bleeding. There have been many investigations in the field and, in recent years, results have confirmed the role of potential marine molecules as alternative antithrombotics. Nonetheless, further clinical studies are required. This review covers the core of the data available so far regarding the science of marine molecules with potential medical applications to treat thrombosis. After a general discussion about the major biochemical steps involved in this pathology, we discuss the key structural and biomedical aspects of marine molecules of both low and high molecular weight endowed with antithrombotic/anticoagulant properties.

Highlights

  • Cardiovascular diseases are a major contributor to the global disease burden

  • The results demonstrated the potential inhibitory effect of PLs on platelet aggregation induced by the mentioned small molecules

  • The results showed that PL from salmon head could strongly inhibit (IC50 = ~90 μg) thrombin-induced platelet aggregation, those from salmon heads (SHs)

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Summary

Introduction

Cardiovascular diseases are a major contributor to the global disease burden. Behind most cardiovascular diseases, such as myocardial infarction, ischemic stroke and coronary artery disease, lies a pathological condition—thrombosis [1,2]. Thrombosis is a diseased state which involves the formation of a blood clot in the vessels of the cardiovascular system. A pathological blood clot formation in the arteries is called an atherothrombosis, while in the veins this is known as a venous thrombosis. The development of a thrombus is primarily attributed to the damaged endothelial lining of vessels [5], the hypercoagulable state, and arterial and/or venous blood stasis [4]. Arterial thrombosis is generally caused by the disruption of an atherosclerotic plaque, leading to the recruitment of platelets and causing adhesion, aggregation and eventual thrombus formation [5]. The tissue factor triggers a coagulation cascade, again leading to the formation of a fibrinous rich blood clot in the venous vessels [4,8,14]. The signs, symptoms and severity of a thrombosis vary depending on the location of the thrombus and on various other molecular/cellular factors which determine the treatment regimen to be followed in a subject specific manner

Current Antithrombotics
Challenges Associated with Current Antithrombotics
Marine Antithrombotics
Organic Small Molecules
Polyphenols
Sphingosines
Terpenes
Benzoic Acid Derivative
Alkaloids
Lipids
Peptides
Proteins
Sulfated Glycans
Findings
Concluding Remarks
Full Text
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