Mutant apolipoprotein A-1 polypeptide with increased resistance to oxidation and reactive carbonyls

An isolated oxidation resistant mutant apolipoprotein A-I (apoA-I) polypeptide comprising:

• an amino acid sequence having at least 85% amino acid sequence identity to the amino acid sequence of SEQ ID NO:4, the mutant apoA-I polypeptide comprising a combination of:
• (1) a conservative amino acid substitution at the residue corresponding to Tyr192 of the amino acid sequence of SEQ ID NO:3;
• and
• (2) at least one conservative amino acid substitution at the residue corresponding to Met86, Met112, or Met148 of the amino acid sequence of SEQ ID NO:3,
• wherein the oxidation resistant mutant apoA-I polypeptide is more resistant to modification by an oxidizing agent as compared to an apoA-I polypeptide comprising the amino acid sequence of SEQ ID NO:3 and interacts with ATP-binding cassette transporter A1 (ABCA1) and promotes ABCA1-mediated cholesterol efflux activity.