The Role of Furin and Its Therapeutic Potential in Cardiovascular Disease Risk.

Fry, Hannah; Mazidi, Mohsen; Kartsonaki, Christiana; Clarke, Robert; Walters, Robin G.; Chen, Zhengming; Millwood, Iona Y.

Furin is an important proteolytic enzyme, converting several proteins from inactive precursors to their active forms. Recently, proteo-genomic analyses in European and East Asian populations suggested a causal association of furin with ischaemic heart disease, and there is growing interest in its role in cardiovascular disease (CVD) aetiology. In this narrative review, we present a critical appraisal of evidence from population studies to assess furin's role in CVD risk and potential as a drug target for CVD. Whilst most observational studies report positive associations between furin expression and CVD risk, some studies report opposing effects, which may reflect the complex biological roles of furin and its substrates. Genetic variation in FURIN is also associated with CVD and its risk factors. We found no evidence of current clinical development of furin as a drug target for CVD, although several phase 1 and 2 clinical trials of furin inhibitors as a type of cancer immunotherapy have been completed. The growing field of proteo-genomics in large-scale population studies may inform the future development of furin and other potential drug targets to improve the treatment and prevention of CVD.

EAST Asians; PROTEOLYTIC enzymes; DRUG target; DRUG development; GENETIC variation

International Journal of Molecular Sciences, 2024, Vol 25, Issue 17, p9237

1661-6596

Academic Journal

10.3390/ijms25179237