Regulation of Very-Low-Density Lipoprotein Receptor in Hypertrophic Rat Heart

• Published in: Circulation research Vol. 78; no. 1; pp. 8 - 14
• Main Authors: Masuzaki, Hiroaki, Jingami, Hisato, Matsuoka, Naoki, Nakagawa, Osamu, Ogawa, Yoshihiro, Mizuno, Megumi, Yoshimasa, Yasunao, Yamamoto, Tokuo, Nakao, Kazuwa
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 01.01.1996; Lippincott; Lippincott Williams & Wilkins Ovid Technologies
• Subjects: Animals; Biological and medical sciences; Cardiology. Vascular system; Cardiomegaly - metabolism; Cells, Cultured; Down-Regulation; Endothelins - pharmacology; Heart; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Lipoprotein Lipase - metabolism; Lipoproteins, VLDL - metabolism; Medical sciences; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, LDL - metabolism; RNA, Messenger - analysis; Heart; Hypertension; Lipoprotein VLDL; Rat; Rodentia; Cardiovascular disease; Hereditary; In vitro; Myocyte; Vertebrata; Mammalia; Heart disease; Animal; Predisposition; Hypertrophy; Biological receptor
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.res.78.1.8

To elucidate the regulation of very-low-density lipoprotein (VLDL) receptor, we have studied its gene expression in the heart of spontaneously hypertensive rats-stroke prone (SHR-SP, an animal model for hypertension-induced cardiac hypertrophy) compared with Wistar-Kyoto rats. RNase protection assay showed that ventricular VLDL receptor mRNA falls to 41% of normal levels at 4 weeks, when hypertension is not yet fully developed, and drops further to 14% at 13 weeks, when cardiac hypertrophy is established. Lipoprotein lipase mRNA decreases in parallel with VLDL receptor mRNA. In cultured neonatal rat ventricular cardiomyocytes, VLDL receptor mRNA decreases in parallel with the process of cardiocyte hypertrophy during the 24 hours after treatment with 10 8 mol/L endothelin-1, falling to 40% of the initial value. These results demonstrate that there is downregulation of VLDL receptor gene expression in cardiac hypertrophy both in vivo and in vitro and suggest that the regulation of the VLDL receptor is possibly linked with the switch in energy substrate from lipid to glucose known to occur in cardiac hypertrophy.(Circ Res. 1996;78:8-14.)