ABCA1-targeting peptide alleviates atherosclerosis via counteracting endothelial dysfunction.

Time for primary review: 16 days Atherosclerosis, characterized by lipid accumulation and chronic inflammation in arteries, is a key driver of adverse cardiovascular events like myocardial infarction.1 Adenosine triphosphate (ATP)-binding cassette (ABC) A1 (ABCA1) modulates cholesterol efflux and inflammation in atherosclerosis,2 thus emerging as a promising therapeutic target. Here, we designed an ABCA1-targeted peptide, named DL-21, to evaluate its anti-atherosclerotic function and related mechanism behind. Animal experiments were conducted according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals, with the approval of the Center for New Drug Safety Evaluation and Research, China Pharmaceutical University No. B20220407-1. Age-matched male Ldlr−/− mice (GemPharmatech) were first fed with a high-fat diet (HFD, Research Diets, #D12109C) for 8 weeks, followed by switching to chow diet and treating with intravenous saline or DL-21 (300 μg/mouse, every other day) for 2 weeks. An independent replicate experiment was conducted using female animals to verify the sex-independence of the findings. All mice were anesthetized with 2% isoflurane and euthanized by cervical dislocation prior to tissue collection.