Protease-sensitive site in apolipoprotein A1, therapeutic and diagnostic implications

摘要

The invention relates to the identification of a naturally occurring internal proteolytic cleavage site in the ApoA1 protein, which leads to inactivation of the mature protein. Specific modification of this cleavage site leads to a stabilised ApoA1 protein, which is beneficial for the reverse cholesterol transport. The invention therefore encompasses pharmaceutical compositions comprising a recombinant stabilised variant ApoA1 protein or rHDL particles comprising such a protein, for use in the treatment of patients having reduced HDL or hampered reverse cholesterol transport.