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Role of Kir6.2 subunits of ATP-sensitive potassium channels in endotoxemia-induced cardiac dysfunction
- Source :
- Cardiovascular Diabetology
- Publisher :
- Springer Nature
-
Abstract
- Background Cardiac dysfunction is well-described in endotoxemia and diagnosed in up to 60% of patients with endotoxic shock. ATP-sensitive potassium (KATP) channels are critical to cardiac function. This study investigates the role of Kir6.2 subunits of KATP channels on cardiac dysfunction in lipopolysaccharide (LPS)-induced endotoxemia. Methods Kir6.2 subunits knockout (Kir6.2−/−) and wild-type (WT) mice were injected with LPS to induce endotoxemia. Cardiac function was monitored by echocardiography. Left ventricles were taken for microscopy (both light and electron) and TUNEL examination. Serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities, and tumor necrosis factor-α (TNF-α) levels in both serum and left ventricular tissues were determined. Results Compared to WT, Kir6.2−/− mice showed significantly declined cardiac function 360 min after LPS administration, aggravated myocardial damage and elevated serum LDH and CK activities. Apoptotic cells were obviously increased in heart tissues from Kir6.2−/− mice at 90, 180 and 360 min. TNF-α expression in both serum and heart tissues of Kir6.2−/− mice was significantly increased. Conclusions We conclude that Kir6.2 subunits are critical in resistance to endotoxemia-induced cardiac dysfunction through reducing myocardial damage by inhibition of apoptosis and inflammation. KATP channels blockers are extensively used in the treatment of diabetes, their potential role should therefore be considered in the clinic when patients treated with antidiabetic sulfonylureas are complicated by endotoxemia.
- Subjects :
- Cardiac function curve
Lipopolysaccharides
Male
medicine.medical_specialty
endocrine system
Lipopolysaccharide
Heart Ventricles
Endocrinology, Diabetes and Metabolism
Inflammation
Apoptosis
chemistry.chemical_compound
Mice
Ventricular Dysfunction, Left
KATP Channels
Internal medicine
medicine
Animals
Potassium Channels, Inwardly Rectifying
Creatine Kinase
Original Investigation
Kir6.2 subunits
Mice, Knockout
TUNEL assay
biology
L-Lactate Dehydrogenase
business.industry
Myocardium
Potassium channel
Endotoxemia
Disease Models, Animal
Endocrinology
chemistry
Echocardiography
biology.protein
Cardiac dysfunction
cardiovascular system
Creatine kinase
Tumor necrosis factor alpha
medicine.symptom
business
Cardiology and Cardiovascular Medicine
Subjects
Details
- Language :
- English
- ISSN :
- 14752840
- Volume :
- 12
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Cardiovascular Diabetology
- Accession number :
- edsair.doi.dedup.....be1f5931927623ee7eb7b55edddb4368
- Full Text :
- https://doi.org/10.1186/1475-2840-12-75