Heparin: An essential drug for modern medicine.Prog Mol Biol Transl Sci 2019; 163:1-19PM
Heparin is a life-saving drug, which belongs to few clinically used drugs without defined molecular structures in modern medicine. Heparin is the mostly negatively charged biopolymer with a broad distributions in molecular weight, charge density, and biological activities. Heparin is mainly composed of repeating trisulfated disaccharide units, which is made by mast cells that are enriched in the intestines, lungs or livers of animals. Porcine intestines and bovine lungs are two mostly used sources for heparin isolation. Heparin is well known for its anticoagulant and antithrombotic pharmacological effects. The anticoagulant activity of heparin is attributable to a 3-O-sulfate and 6-O-sulfate containing pentasaccharide sequence or a minimum eight-repeating disaccharide units containing the pentasaccharide sequence that catalyzes the suicidal inactivation of factor Xa or thrombin by a serpin or serine protease inhibitor named antithrombin III, respectively. Thus, heparin is responsible for the simultaneous inhibition of both thrombin generation and thrombin activity in the blood circulation. Moreover, heparin has many pharmacological properties such as anti-inflammatory, anti-viral, anti-angiogenesis, anti-neoplastic, and anti-metastatic effects though high affinity interactions with a variety of proteases, protease inhibitors, chemokines, cytokines, growth factors, and their respective receptors. The one drug multiple molecular targeting properties make heparin a very special drug in that various clinical trials are still conducting worldwide even 100 years after its discovery. In this review, we will summarize the structure-function relationship and the molecular mechanisms of heparin. We will also provide an overview of different clinical and potential clinical applications of heparin.