Impaired myofibrillar energetics and oxidative injury during human atrial fibrillation
Summary
This summary is machine-generated.Oxidative damage in atrial fibrillation (AF) reduces myofibrillar creatine kinase (MM-CK) activity, impairing heart contractility. Protein nitration is implicated in this dysfunction, suggesting new therapeutic targets for AF-related heart failure.
Area Of Science
- Cardiology
- Biochemistry
- Molecular Biology
Background
- Atrial fibrillation (AF) causes severe cardiac dysfunction, but underlying mechanisms remain unclear.
- Current therapies for AF do not address the associated contractile dysfunction.
- Myofibrillar creatine kinase (MM-CK) is crucial for myocyte contractility and sensitive to oxidative stress.
Purpose Of The Study
- To investigate the role of oxidative stress and energetic impairment in AF-related contractile dysfunction.
- To determine if MM-CK activity is altered in human AF.
- To identify specific oxidative modifications contributing to MM-CK dysfunction in AF.
Main Methods
- Human right atrial appendages from AF patients and control subjects were analyzed.
- Myofibrillar MM-CK activity, total CK activity, and myosin ATPase activity were measured.
- Protein expression (beta-myosin isoform) and oxidative damage (3-nitrotyrosine, protein carbonyls) were assessed using Western blotting.
Main Results
- MM-CK activity was significantly reduced in AF patients compared to controls.
- No changes were observed in total CK or myosin ATPase activity, indicating selective MM-CK impairment.
- Increased protein oxidation, specifically nitration and carbonylation, was detected in AF myofibrils.
- MM-CK inhibition correlated with protein nitration, but not carbonylation.
Conclusions
- Novel evidence of oxidative damage in human AF is presented.
- Altered myofibrillar energetics due to oxidative stress likely contribute to atrial contractile dysfunction.
- Protein nitration emerges as a significant factor in AF-related cardiac dysfunction.
View abstract on PubMed