Malondialdehyde-modified apolipoprotein B-100 peptide 661–680 (MDA-p45)

Malondialdehyde-modified apolipoprotein B-100 peptide 661–680, commonly referred to as MDA-p45, is a specific oxidative neo-epitope found on oxidized low-density lipoprotein (oxLDL) particles. During the process of LDL oxidation, malondialdehyde (MDA) is generated as a byproduct of lipid peroxidation and covalently modifies the lysine residues of apolipoprotein B-100, particularly within the p45 sequence. This modification transforms the native protein into a pro-inflammatory and immunogenic molecule that is recognized by scavenger receptors on macrophages, leading to foam cell formation and the progression of atherosclerosis. Interestingly, natural autoantibodies against MDA-p45 have been identified in humans and are inversely correlated with the severity of cardiovascular disease, suggesting a protective role for the immune response against this epitope. Therapeutic interventions, such as the monoclonal antibody Orticumab (BI-204), have been developed to target this sequence to promote the clearance of oxLDL and reduce arterial inflammation. While experimental models showed significant reduction in plaque size, clinical trials have faced challenges in demonstrating consistent efficacy in patients with established cardiovascular disease.

Other names

p45MDA-p45Apolipoprotein B-100 peptide 661–680Malondialdehyde-modified ApoB-100 sequence 661–680Oxidized low-density lipoprotein epitope p45

Passive immunization with a monoclonal antibody that specifically binds to the MDA-modified p45 epitope of oxidized low-density lipoprotein to inhibit macrophage activation, promote the clearance of pro-inflammatory lipid particles, and reduce plaque inflammation.