title: Apolipoprotein A-I Mimetic Peptide D-4F Reduces Cardiac Hypertrophy and Improves Apolipoprotein A-I-Mediated Reverse Cholesterol Transport From Cardiac Tissue in LDL Receptor-null Mice Fed a Western Diet.
abstract: Epidemiological studies have suggested that hypercholesterolemia is an independent determinant of increased left ventricular (LV) mass. Because high-density lipoprotein and its major protein apolipoprotein A-I (apoA-I) mediate reverse cholesterol transport (RCT) and have cardiac protective effects, we hypothesized that the apoA-I mimetic peptide D-4F could promote RCT in cardiac tissue and decrease cardiac hypertrophy induced by hypercholesterolemia. Low-density lipoprotein receptor-null mice were fed by a Western diet for 18 weeks and then randomized to receive water, or D-4F 0.3 mg/mL, or D-4F 0.5 mg/mL added to drinking water for 6 weeks. After D-4F administration, an increase in high-density lipoprotein cholesterol and a decrease in low-density lipoprotein cholesterol, total cholesterol, and triglyceride in a trend toward dose-responsivity were found in cardiac tissue. Ultrasound biomicroscopy revealed a reduction in LV posterior wall end-diastolic dimension, and an increase in mitral valve E/A ratio and LV ejection fraction. Hematoxylin-eosin staining showed reduced LV wall thickness and myocardial cell diameter. The protein levels of ABCA1 and LXRα were elevated in cardiac tissue of D-4F treated mice compared with the controls (P < 0.05). These results demonstrated that D-4F treatment reduced cardiac hypertrophy, and improved cardiac performance in low-density lipoprotein receptor-null mice fed a Western diet, presumably through the LXRα-ABCA1 pathway associated with enhanced myocardial RCT.
authors.affiliation: *Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, China; †Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China; ‡Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, China; and §Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Han
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Ye
authors.forename: Yong-Xue
authors.initials: YX
authors.lastname: Liu
authors.forename: Yan-Wen
authors.initials: YW
authors.lastname: Qin
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Miao
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000096:biosynthesis; D000818:Animals; D016632:Apolipoprotein A-I / Q000494:pharmacology*; D001692:Biological Transport; D006332:Cardiomegaly / Q000209:etiology / Q000503:physiopathology*; D002784:Cholesterol / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism; D066273:Diet, Western; D005260:Female; D006937:Hypercholesterolemia / Q000150:complications; D000071518:Liver X Receptors / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D014280:Triglycerides / Q000378:metabolism
chemical_list: D064286:ATP Binding Cassette Transporter 1; D016632:Apolipoprotein A-I; D008078:Cholesterol, LDL; C465468:D-4F peptide; D000071518:Liver X Receptors; D014280:Triglycerides; D002784:Cholesterol