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Updated: May 17, 2025
07:14
A Flow Cytometry-based Assay for Measuring Mitochondrial Membrane Potential in Cardiac Myocytes After Hypoxia/Reoxygenation
Published on: July 13, 2018
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JAK2/STAT3/HMGCS2 signaling aggravates mitochondrial dysfunction and oxidative stress in hyperuricemia-induced
Dewei Peng1,2, Xiaoli He1,2, Bowen Ren1,2
1Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Molecular Medicine (Cambridge, Mass.)
|May 13, 2025
Summary
High uric acid damages the heart by affecting mitochondrial function and energy metabolism via the JAK2/STAT3/HMGCS2 pathway. Targeting this pathway may offer a new treatment for hyperuricemia-related cardiac dysfunction.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Metabolic Disorders
Background:
- Elevated uric acid levels are implicated in cardiovascular disease development and progression.
- Understanding the molecular mechanisms of hyperuricemia-induced cardiac damage is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of the JAK2/STAT3/HMGCS2 signaling pathway in hyperuricemia-induced cardiac dysfunction.
- To explore the therapeutic potential of targeting this pathway for cardiovascular protection.
Main Methods:
- Transcriptomic analysis of myocardial tissue from a hyperuricemic mouse model.
- Investigated HMGCS2 function in cardiomyocytes using knockout and overexpression models.
- Explored STAT3 regulation of HMGCS2 via knockdown and reporter assays.
- Assessed therapeutic efficacy of JAK2/STAT3 inhibitors in vivo and in vitro.
Main Results:
- Uric acid upregulated HMGCS2 expression in cardiac tissue and cardiomyocytes.
- HMGCS2 knockdown ameliorated uric acid-induced mitochondrial dysfunction, oxidative stress, and metabolic abnormalities.
- The IL-6/JAK2/STAT3 pathway was identified as a regulator of HMGCS2 expression.
- JAK2/STAT3 pathway inhibition reversed cardiac dysfunction and improved mitochondrial function in hyperuricemic mice.
Conclusions:
- The JAK2/STAT3/HMGCS2 pathway contributes to uric acid-induced cardiac dysfunction.
- Targeting the JAK2/STAT3/HMGCS2 pathway presents a promising therapeutic strategy for hyperuricemia-related cardiac damage.
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