High molecular weight kininogen contributes to early mortality and kidney dysfunction in a mouse model of sickle cell disease.

CONCLUSIONS: We found elevated plasma levels of cleaved HK in sickle patients compared to healthy controls, suggesting ongoing HK activation in SCD. We used bone marrow transplantation to generate wild type and sickle cell mice on a HK-deficient background. We found that short-term HK deficiency attenuated thrombin generation and inflammation in sickle mice at steady state, which was independent of bradykinin signaling. Moreover, long-term HK deficiency attenuates kidney injury, reduces chronic inflammation, and ultimately improves of sickle mice.
PMID: 32573897 [PubMed - as supplied by publisher]

Source: Thrombosis and Haemostasis - June 22, 2020 Category: Hematology Authors: Sparkenbaugh EM, Kasztan M, Henderson MW, Ellsworth P, Davis PR, Wilson KJ, Reeves B, Key NS, Strickland S, McCrae K, Pollock DM, Pawlinski R Tags: J Thromb Haemost Source Type: research