Key result
Caveolin-1 ablation induces cardiac hypertrophy and dysfunction, increasing fatty acid uptake by ~47%.
Why the study?
The metabolic phenotype associated with caveolin-1 gene ablation in cardiac fibroblasts and its impact on cardiac hypertrophy and substrate metabolism was not well characterized.
Preclinical caveolin-1 ablation data remain hypothesis-generating; leaves open its relevance to human metabolic cardiomyopathy.
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. Microarray gene expression analysis revealed changes in genes that regulate calcium ion and lipid transport as well as a number of genes not previously linked to cardiac hypertrophy. We observed a 4-fold increase in tetraspanin-2 gene expression, a transmembrane protein implicated in regulating intracellular trafficking. Oxysterol binding protein related protein-3, which has been implicated in intracellular lipid synthesis and transport, was increased 3.6-fold. In addition, sarcoplasmic reticulum Ca(2+)-ATPase 3, and calcyclin gene transcripts were significantly increased in Cav1ko hearts. In summary, targeted loss of Cav1 produces a unique model of cardiac hypertrophy with normal substrate utilization and expression of genes involved in energy metabolism.
No takes yet. Share an insight, caveat, or question.
Augustus et al. (2008) studied Cardiac hypertrophy. Caveolin-1 (Cav1) gene ablation vs. Wild-type (implicit) was evaluated on Metabolic phenotype and substrate utilization. Caveolin-1 gene ablation resulted in cardiac hypertrophy and contractile dysfunction at 5-6 months of age, with increased myocardial uptake of triglyceride (25%) and albumin-bound fatty acids (47%).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: