Hearts lacking caveolin-1 develop hypertrophy with normal cardiac substrate metabolism

Cell Cycle
Ayanna S AugustusM P Lisanti

Abstract

Long-chain fatty acids (FA) are the primary energy source utilized by the adult heart. However, during pathological cardiac hypertrophy the fetal gene program is reactivated and glucose becomes the major fuel source metabolized by the heart. Herein we describe the metabolic phenotype associated with caveolin-1(Cav1) gene ablation (Cav1ko) in cardiac fibroblasts. Cav1, the primary protein component of caveolae in non-muscle cells co-localizes with a number of proteins involved in substrate metabolism, including, FA translocase (CD36) and the insulin receptor. We demonstrate that Cav1ko hearts develop cardiac hypertrophy and contractile dysfunction at 5-6mos of age. Surprisingly, we observed an increase in the uptake of Intralipid triglyceride and albumin bound FA by 25% and 47%, respectively, in Cav1ko hearts. Isolated perfused heart studies revealed no significant difference in glucose oxidation and glycolysis, however, we observed a trend toward increased FA oxidation in Cav1ko hearts. Real-time PCR analysis revealed no significant changes in the expression of genes involved in FA and glucose metabolism. We also report myocardial triglyceride, fatty acid and cholesterol levels are significantly reduced in Cav1ko hearts. Microa...Continue Reading

Citations

Jan 24, 2018·Molecular Pharmacology·Jan M SchillingHemal H Patel
Nov 9, 2019·Circulation. Genomic and Precision Medicine·Charlotte AnderssonRamachandran S Vasan
Jul 7, 2020·Frontiers in Cellular and Infection Microbiology·Lindice M NisimuraDaniel Adesse
Feb 6, 2020·Biochemical Society Transactions·Cerrone R FosterHemal H Patel
Feb 11, 2021·Annual Review of Physiology·Weiling XuSerpil C Erzurum

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