A purification experiment of heparin cofactor II was performed in 1981, in which it was discovered that the purified version of the protein consists of a single polypeptide chain.[6] Further experimentation demonstrated that whether β-Mercaptoethanol is present does not affect HCII's activity in gel electrophoresis. β-Mercaptoethanol is typically used for the reduction of disulfide bonds within a molecule, but the gel electrophoresis revealed that HCII does not have any of these bonds. The structure is similar to antithrombin III (ATIII), which was known to effectively inhibit thrombin as well as coagulation factor Xa.[6] This experiment suggested that HCII has strong thrombin inhibition, yet weak inhibition of coagulation factor Xa.
Heparin cofactor II may play a role in the immune response, as it has been associated with leukocyte-mediated protein degradation, which releases cytokines in the inflammatory response with neutrophils and monocytes.[7] Its role has been questioned because although it is a thrombin inhibitor, an absence of HCII does not result in significantly higher levels of thrombosis.[7] This does not negate the results of the 1981 study, but novel discoveries create more questions of the biological mechanism and function of the protein. However, this cofactor shows stronger capability in inhibiting thrombin in pregnant women, protecting them from thrombosis. Pregnant women have shown increased levels of heparin cofactor II as well as dermatan sulfate, which is a polysaccharide that is expected to be involved in wound repair, coagulation, and overall maintenance throughout the body. Pregnant women who had thrombosis are likely to also have low levels of heparin cofactor II, but whether this is a causation is still unknown.[8]
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Uszyński M (1992). "Tissue anticoagulants in the human placenta: preliminary study with a heparin-like anticoagulant and review of the literature". Gynecol. Obstet. Invest. 32 (3): 129–33. doi:10.1159/000293013. PMID1836773.
Sutherland JS, Bhakta V, Filion ML, Sheffield WP (2006). "The transferable tail: fusion of the N-terminal acidic extension of heparin cofactor II to alpha1-proteinase inhibitor M358R specifically increases the rate of thrombin inhibition". Biochemistry. 45 (38): 11444–52. doi:10.1021/bi0609624. PMID16981704.
Schillinger M, Exner M, Sabeti S, et al. (2005). "High plasma heparin cofactor II activity protects from restenosis after femoropopliteal stenting". Thromb. Haemost. 92 (5): 1108–13. doi:10.1160/TH04-05-0311. PMID15543340. S2CID13806207.
Zhang F, Wu Y, Ma Q, et al. (2004). "Studies on the effect of calcium in interactions between heparin and heparin cofactor II using surface plasmon resonance". Clin. Appl. Thromb. Hemost. 10 (3): 249–57. doi:10.1177/107602960401000307. PMID15247982. S2CID21405427.
Cunningham MA, Bhakta V, Sheffield WP (2003). "Altering heparin cofactor II at VAL439 (P6) either impairs inhibition of thrombin or confers elastase resistance". Thromb. Haemost. 88 (1): 89–97. doi:10.1055/s-0037-1613159. PMID12152684. S2CID1467230.
Hayakawa Y, Hirashima Y, Kurimoto M, et al. (2002). "Contribution of basic residues of the A helix of heparin cofactor II to heparin- or dermatan sulfate-mediated thrombin inhibition". FEBS Lett. 522 (1–3): 147–50. doi:10.1016/S0014-5793(02)02930-7. PMID12095635. S2CID12634527.
Böhme C, Nimtz M, Grabenhorst E, et al. (2002). "Tyrosine sulfation and N-glycosylation of human heparin cofactor II from plasma and recombinant Chinese hamster ovary cells and their effects on heparin binding". Eur. J. Biochem. 269 (3): 977–88. doi:10.1046/j.0014-2956.2001.02732.x. PMID11846800.
