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Cathepsin K knockout protects against cardiac dysfunction in diabetic mice
Rui Guo1, Yinan Hua1, Olivia Rogers1
1School of Pharmacy, College of Health Sciences and the Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, WY, 82071, USA.
Scientific Reports
|August 20, 2017
Summary
Cathepsin K knockout protects against diabetic heart disease by reducing cardiac dysfunction, apoptosis, and oxidative stress. This suggests targeting cathepsin K could treat diabetes-associated cardiac complications.
Area of Science:
- Cardiology
- Endocrinology
- Molecular Biology
Background:
- Diabetes mellitus is a significant risk factor for cardiovascular disease.
- The lysosomal cysteine protease cathepsin K is implicated in cardiac pathophysiology.
Purpose of the Study:
- To investigate the protective role of cathepsin K knockout against diabetes-associated cardiac anomalies.
- To determine if cathepsin K deficiency mitigates cardiac dysfunction in a mouse model of diabetes.
Main Methods:
- Streptozotocin (STZ) induced diabetes in wild-type and cathepsin K knockout mice.
- Assessed body weight, organ mass, blood glucose, energy expenditure, cardiac function, and histomorphology.
- Measured glutathione levels, and protein expression related to calcium handling, calcineurin/NFAT, insulin signaling, apoptosis, and fibrosis.
Main Results:
- STZ-induced diabetes caused cardiac dysfunction, altered calcium handling, morphological changes, and increased cardiomyocyte apoptosis.
- Cathepsin K knockout mice showed mitigated cardiac dysfunction, apoptosis, and oxidative stress.
- Cathepsin K knockout attenuated calcineurin/NFAT signaling in diabetic hearts.
- Pharmacological inhibition of cathepsin K protected cultured cells from high-glucose induced damage.
Conclusions:
- Cathepsin K plays a detrimental role in diabetes-associated cardiac dysfunction.
- Cathepsin K knockout offers protection against diabetic cardiomyopathy.
- Targeting cathepsin K presents a potential therapeutic strategy for managing diabetic heart disease.
