ABCA1, also known as ATP-binding cassette transporter A1, is a key protein in lipid metabolism. It mediates the cellular efflux of phospholipids and cholesterol to lipid-poor apolipoprotein A1 (apoA1), playing a significant role in high-density lipoprotein (HDL) metabolism and reverse cholesterol transport (RCT) pathway [3,4,5]. ABCA1 is also involved in processes like apoptosis, inflammation, and efferocytosis, which are crucial for maintaining normal physiological functions [2,3]. Genetic models, such as gene-knockout (KO) mouse models, have been instrumental in studying ABCA1.

In a type 2 diabetic mouse model with ABCA1 deficiency in glomerular endothelial cells (DM-ABCA1-/-mice), ABCA1 deficiency exacerbated renal lipid deposition and kidney injuries, including increased creatinine levels, severe proteinuria, mesangial matrix expansion, and more pronounced renal inflammatory injury and cell death [1]. In atherosclerotic research, ABCA1-deficient mouse models and in vitro experiments suggest that ABCA1 not only mediates cholesterol and phospholipid efflux but also regulates apoptosis and inflammation, indicating its importance in atherosclerosis development [3].

In conclusion, ABCA1 is essential for lipid homeostasis, efferocytosis, and the regulation of apoptosis and inflammation. The study of ABCA1 using KO mouse models has revealed its significant roles in diseases such as diabetic kidney disease and atherosclerosis. Understanding ABCA1's functions provides potential therapeutic targets for these diseases [1,2,3].

References:

1. Zhang, Junlin, Wu, Yucheng, Zhang, Jie, Wang, Yiting, Liu, Fang. 2022. ABCA1 deficiency-mediated glomerular cholesterol accumulation exacerbates glomerular endothelial injury and dysfunction in diabetic kidney disease. In Metabolism: clinical and experimental, 139, 155377. doi:10.1016/j.metabol.2022.155377. https://pubmed.ncbi.nlm.nih.gov/36521550/

2. Chen, Wujun, Li, Lu, Wang, Jie, Wang, Shuai, Xing, Dongming. 2021. The ABCA1-efferocytosis axis: A new strategy to protect against atherosclerosis. In Clinica chimica acta; international journal of clinical chemistry, 518, 1-8. doi:10.1016/j.cca.2021.02.025. https://pubmed.ncbi.nlm.nih.gov/33741356/

3. Soumian, S, Albrecht, C, Davies, A H, Gibbs, R G J. . ABCA1 and atherosclerosis. In Vascular medicine (London, England), 10, 109-19. doi:. https://pubmed.ncbi.nlm.nih.gov/16013195/

4. Phillips, Michael C. 2018. Is ABCA1 a lipid transfer protein? In Journal of lipid research, 59, 749-763. doi:10.1194/jlr.R082313. https://pubmed.ncbi.nlm.nih.gov/29305383/

5. Wang, Shuhui, Smith, Jonathan D. 2014. ABCA1 and nascent HDL biogenesis. In BioFactors (Oxford, England), 40, 547-54. doi:10.1002/biof.1187. https://pubmed.ncbi.nlm.nih.gov/25359426/