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Endothelial binding sites for lipoprotein lipase are not diminished in perfused hearts from diabetic rats
1Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Canada.
Insights
Diabetes does not affect how lipoprotein lipase (LPL) binds to heart blood vessels. This study found that the enzyme
Area of Science:
- Cardiovascular Biology
- Metabolic Diseases
- Enzymology
Background:
- Diabetes mellitus is associated with altered lipid metabolism and cardiovascular complications.
- Lipoprotein lipase (LPL) plays a crucial role in triglyceride hydrolysis and is found in the coronary vasculature.
- Reduced functional, heparin-releasable LPL (HR-LPL) activity in diabetes could impact cardiac lipid utilization.
Purpose of the Study:
- To investigate whether diabetes alters endothelial binding sites for LPL in the heart.
- To determine if changes in LPL binding contribute to reduced HR-LPL activity in diabetic hearts.
Main Methods:
- Perfused rat hearts with heparin to release endogenous LPL.
- Measured binding and heparin-induced release of exogenous bovine milk LPL (mLPL) in control and diabetic hearts.
- Induced diabetes using streptozotocin.
Main Results:
- Diabetes reduced endogenous HR-LPL activity.
- Binding and heparin-induced release of exogenous mLPL were unchanged in diabetic hearts compared to controls.
- Proteoglycan binding sites for mLPL on the endothelium remained unaffected by diabetes.
Conclusions:
- Diabetes does not alter the low-affinity, high-capacity proteoglycan binding sites for LPL on the cardiac endothelium.
- The reduced HR-LPL activity in diabetes is not due to altered endothelial binding capacity.
- Further research is needed to identify the mechanisms behind diabetes-associated reductions in HR-LPL activity.
Abstract:
The possibility that diabetes reduces functional, heparin-releasable lipoprotein lipase (HR-LPL) activity on the coronary vasculature of perfused hearts by altering endothelial binding sites for the enzyme was examined by measuring the binding and subsequent heparin-induced release of exogenous lipoprotein lipase purified from bovine milk (mLPL). Rat hearts were first perfused with heparin (5 U/mL) for 5 min to displace endogenous HR-LPL into the perfusate. The subsequent perfusion of control hearts with 0.05-2 micrograms/mL mLPL resulted in a progressive increase in bound exogenous enzyme that could be released by a second heparin perfusion. Induction of an acute, insulin-deficient model of diabetes (100 mg/kg streptozotocin 4-5 days prior to heart perfusions) reduced endogenous HR-LPL activity, but the binding and heparin-induced release of mLPL (0.5 microgram/mL) were the same as measured in control hearts. Therefore, diabetes does not alter low-affinity, high-capacity proteoglycan binding sites for mLPL on the endothelium of perfused hearts.