A cyclic azapeptide ligand of the scavenger receptor CD36/SR-B2 reduces the atherosclerotic lesion progression and enhances plaque stability in apolipoprotein E-deficient mice

Atherosclerosis is a chronic inflammatory disease of the arterial walls that develops at predisposed sites. As a major risk factor for adverse cardiovascular pathology, atherosclerosis can progress to myocardial infarction and stroke, due to the rupture of unstable atherosclerotic lesions. Macrophage uptake of modified lipoproteins and metabolic dysfunction contributes significantly to the initiation and development of atherosclerotic lesions. The cluster of differentiation 36 receptor [CD36 (SR-B2)] plays a key role in atherosclerotic lesion progression and acts as an efferocytic molecule in the resolution of advanced plaque. In previous studies, linear azapeptide CD36 ligands were shown to exhibit anti-atherosclerotic properties. In the present study, a novel potent and selective macrocyclic azapeptide CD36 ligand, MPE-298, has proven effective in protecting against atherosclerosis progression. Features of greater plaque stability were observed after 8 weeks of daily injections with the cyclic azapeptide in apolipoprotein E-deficient mice fed a high-fat high-cholesterol diet.

Automated summary

Atherosclerosis is a chronic inflammatory disease that occurs at vulnerable sites in the arterial walls. It is a major risk factor for adverse cardiovascular events such as myocardial infarction and stroke, often due to the rupture of unstable atherosclerotic plaques. Macrophage uptake of modified lipoproteins and metabolic dysfunction significantly contribute to the development and progression of atherosclerotic lesions. The CD36 receptor plays a crucial role in the progression of atherosclerotic lesions and acts as a molecule in the resolution of advanced plaques. This study demonstrates that a novel and selective macrocyclic azapeptide CD36 ligand, MPE-298, effectively protects against the progression of atherosclerosis in mice fed a high-fat high-cholesterol diet, leading to increased plaque stability after 8 weeks of daily injections.