Interplay of defective excitation-contraction coupling, energy starvation, and oxidative stress in heart failure
Michael Kohlhaas1, Christoph Maack
1Medizinische Klinik und Poliklinik, Innere Medizin III, Universitätsklinikum des Saarlandes, 66421 Homburg/Saar, Germany.
Insights
Chronic heart failure involves left ventricle remodeling, impacting cardiac function. This review explores how impaired excitation-contraction coupling, energy deficits, and oxidative stress interact, driven by mitochondrial dysfunction, to worsen heart failure.
Area of Science:
- Cardiovascular Physiology
- Mitochondrial Biology
- Cardiac Pathophysiology
Background:
- Chronic heart failure (CHF) is characterized by maladaptive left ventricular (LV) remodeling, leading to systolic and diastolic dysfunction.
- Key pathological aspects include defects in excitation-contraction (EC) coupling (Ca(2+)/Na(+) homeostasis), cellular energetic deficits, and oxidative stress.
Purpose of the Study:
- To review recent advances in understanding the interplay between EC coupling, energetics, and oxidative stress in CHF.
- To highlight the central role of mitochondria in mediating these interconnected pathological processes.
Main Methods:
- Literature review of recent scientific advances.
- Focus on the dynamic interplay of cellular Ca(2+)/Na(+) homeostasis, ATP production, reactive oxygen species generation, and mitochondrial function.
Main Results:
- Maladaptive changes in EC coupling contribute to energetic deficits and oxidative stress in the failing heart.
- Mitochondria are identified as critical regulators of ATP production and reactive oxygen species, influenced by Ca(2+) and Na(+) levels.
Conclusions:
- The close interplay between EC coupling defects, energetic deficits, and oxidative stress creates a vicious cycle.
- This cycle drives progressive cardiac dysfunction in chronic heart failure, underscoring the importance of mitochondrial health.
Abstract:
In chronic heart failure, maladaptive remodeling of the left ventricle (LV) with systolic and diastolic dysfunction underlies the inability of the heart to pump sufficient blood to supply the body with blood and oxygen. Three integral aspects of this maladaptive LV remodeling are (1) defects in excitation-contraction (EC) coupling, particularly of cellular Ca(2+) and Na(+) homeostasis; (2) an energetic deficit; and (3) oxidative stress. Although these three aspects are often investigated separately from each other, their close and dynamic interplay are increasingly recognized. Central to this novel approach are mitochondria, which are the main source for cellular ATP, but also for reactive oxygen species, and their function is critically regulated by Ca(2+) and Na(+). Here, we review recent advances in our understanding of how maladaptive changes of EC coupling can contribute to the energetic deficit and oxidative stress, which may initiate a vicious cycle leading to progressive cardiac dysfunction.
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