Arterioscler Thromb Vasc Biol 2021 May 13:ATVBAHA120315719. Epub 2021 May 13.
Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, School of Basic Medical Sciences, Peking University, Beijing, China (M.G., W.H., Y.W., G.L., X.X.).
Objective: Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is a rare human disease characterized by very low HDL (high-density lipoprotein) and elevated free cholesterol, in which renal injury has been confirmed in, but whether familial LCAT deficiency patients were at higher risk of atherosclerosis-related cardiovascular disease was highly controversial. Using CRISPR/Cas9 gene-editing technology, we established LCAT knockout (LCAT) hamster model showing both diet-induced and spontaneous atherosclerosis, indicating that this animal model provides a platform for the therapeutic study of renal disease and atherosclerosis caused by LCAT deficiency. Approach and Results: To explore an efficient therapy for familial LCAT deficiency and then investigate whether correction of LCAT deficiency will exert a beneficial role in atherosclerosis-related cardiovascular disease, herein we established a liver-specific adeno-associated virus 8 expressing human LCAT (AAV-hLCAT) to determine the efficacy of gene therapy for dyslipidemia, renal injury, and atherosclerosis-related cardiovascular disease in LCAT hamsters. Read More