REGULATION OF VERY-LOW-DENSITY LIPOPROTEIN RECEPTOR IN HYPERTROPHIC RAT-HEART

To elucidate the regulation of very-low-density lipoprotein (VLDL) rec eptor, we have studied its gene expression in the heart of spontaneous ly hypertensive rats-stroke prone (SHR-SP, an animal model for hyperte nsion-induced cardiac hypertrophy) compared with Wistar-Kyoto rats. RN ase 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 hypertr ophy is established. Lipoprotein lipase mRNA decreases in parallel wit h VLDL receptor mRNA. In cultured neonatal rat ventricular cardiomyocy tes, VLDL receptor mRNA decreases in parallel with the process of card iocyte hypertrophy during the 24 hours after treatment with 10(-8) mol /L endothelin-1, falling to 40% of the initial value. These results de monstrate that there is downregulation of VLDL receptor gene expressio n in cardiac hypertrophy both in vivo and in vitro and suggest that th e regulation of the VLDL receptor is possibly linked with the switch i n energy substrate from lipid to glucose known to occur in cardiac hyp ertrophy.