Submitted on April 5, 2008
Revised on June 25, 2008
Accepted on July 10, 2008
Cardiac Metabolic Compensation to Hypertension Requires Lipoprotein Lipase
Haruyo Yamashita1, Kalyani G Bharadwaj1, Shota Ikeda1, Tae-Sik Park2, and Ira J. Goldberg3*
1 Columbia University
2 Gachon University
3 Columbia University of Physicians and Surgeons
* To whom correspondence should be addressed. E-mail: ijg3{at}columbia.edu.
Fatty acids (FAs) are acquired from free FA associated with albumin and lipoprotein triglyceride that is hydrolyzed by lipoprotein lipase (LpL). Hypertrophied hearts shift their substrate usage pattern to more glucose and less FA. However, FAs may still be an important source of energy in hypertrophied hearts. The aim of this study was to examine the importance of LpL-derived FAs in hypertensive hypertrophied hearts. We followed cardiac function and metabolic changes during 2 weeks of angiotensin II (AngII)-induced hypertension in control and heart specific lipoprotein lipase knockout (hLpL0) mice. Glucose metabolism was increased in AngII-treated control (control/AngII) hearts raising it to the same level as hLpL0 hearts. FA uptake-related genes, CD36 and FATP1, were reduced in control/AngII hearts to levels found in hLpL0 hearts. AngII did not alter these metabolic genes in hLpL0 mice. LpL activity was preserved and mitochondrial FA oxidation-related genes were not altered in control/AngII hearts. In control/AngII hearts, triglyceride stores were consumed and reached the same levels as in hLpL0/AngII hearts. Intracellular ATP content was reduced only in hLpL0/AngII hearts. Both AngII and deoxycorticosterone acetate-salt induced hypertension caused heart failure only in hLpL0 mice. Our data suggest that LpL activity is required for normal cardiac metabolic compensation to hypertensive stress.
