Aliskiren affects fatty-acid uptake and lipid-related genes in rodent and human cardiomyocytes

作者：Rodriguez Penas Diego; Feijoo Bandin Sandra; Lear Pamela V; Mosquera Leal Ana; Garcia Rua Vanessa; Otero Manuel F; Rivera Miguel; Gualillo Oreste; Ramon Gonzalez Juanatey Jose; Lago Francisca^*

来源：Biochemical Pharmacology, 2011, 82(5): 491-504.

DOI：10.1016/j.bcp.2011.05.021

• Cardiomyocytes
• Aliskiren
• Metabolism
• Lipids
• Cholesterol
• Glucose

Purpose: We investigated whether the direct renin inhibitor aliskiren can affect metabolism in cardiomyocytes from rat, mouse and human sources.
Methods and results: At 10-50 mu mol/L, aliskiren significantly increased medium-chain-fatty-acid uptake in primary-cultured neonatal-rat and HL-1 adult-mouse-derived cardiomyocytes (BODIPY-induced fluorescence intensity). The fatty-acid transporter CD-36 was correspondingly translocated to, but the glucose transporter Glut-4 away from, the sarcoplasmic reticulum/plasma membrane, in primary-cultured neonatal-rat (CD-36, Glut-4) and adult-human (CD-36) cardiomyocytes (confocal immunocytochemistry). Immunoblotting showed that aliskiren induced phosphorylation of ERK1/2 in cardiomyocytes from all three sources; responses were dose- and time-dependent, unaffected by renin treatment, and did not cause alterations in expression of (P)R or Igf2/M6P receptors. Microarray analysis of the complete genome of aliskiren-treated neonatal-rat cardiomyocytes, with RT-qPCR and immunoblot confirmation assays in rat and human primary cardiomyocytes, showed that aliskiren up-regulated mRNA and increased protein expression of several enzymes important in lipid and glucose metabolism and in cholesterol biosynthesis. Cardiomyocyte cell-cycle and viability were unaffected by aliskiren.
Conclusions: Aliskiren can induce changes in fatty-acid and glucose uptake and expression of key enzymes of lipid and cholesterol metabolism, which are not associated with increased expression of (P)R or Igf2/M6P receptors, in cultured cardiomyocytes.

• 出版日期2011-9-1