Hypertrophic cardiomyopathy: a heart in need of an energy bar?
Styliani Vakrou1, M Roselle Abraham1
1Division of Cardiology, School of Medicine, Johns Hopkins University Baltimore, MD, USA.
Insights
Hypertrophic cardiomyopathy (HCM), a common inherited heart disorder, involves thickened heart walls and can cause sudden death. This review explores how cellular metabolism and mitochondria dysfunction contribute to HCM development and potential therapies.
Area of Science:
- Cardiovascular Medicine
- Genetics
- Cellular Biology
Background:
- Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiovascular disorder, affecting 1 in 500 adults globally.
- HCM is characterized by myocyte hypertrophy, fibrosis, diastolic dysfunction, and is a leading cause of sudden cardiac death in young individuals.
- While sarcomeric protein mutations are implicated, the precise mechanisms leading to variable cardiac phenotypes remain unclear.
Purpose of the Study:
- To review the evidence linking cellular metabolism and mitochondrial dysfunction to the pathogenesis of hypertrophic cardiomyopathy (HCM).
- To explore the role of metabolic abnormalities and mitochondrial dysfunction in the development of the HCM cardiac phenotype.
- To discuss the therapeutic implications of targeting cellular metabolism and mitochondria in experimental models and patients with HCM.
Main Methods:
- Literature review of studies investigating cellular metabolism in hypertrophic cardiomyopathy.
- Analysis of research on mitochondrial function and dysfunction in the context of HCM.
- Synthesis of evidence from experimental models and clinical studies related to HCM pathophysiology.
Main Results:
- Abnormalities in calcium cycling, oxidative stress, and energetic deficits are frequently observed in HCM.
- Mitochondrial dysfunction contributes significantly to the development of cardiac hypertrophy and fibrosis in HCM.
- Cellular metabolic alterations play a crucial role in the progression of HCM and its associated diastolic dysfunction.
Conclusions:
- Cellular metabolism and mitochondrial function are central to the pathophysiology of hypertrophic cardiomyopathy (HCM).
- Targeting metabolic pathways and improving mitochondrial health represent promising therapeutic strategies for HCM.
- Further research into the metabolic underpinnings of HCM is essential for developing effective treatments.
Abstract:
Hypertrophic cardiomyopathy (HCM) has been recently recognized as the most common inherited cardiovascular disorder, affecting 1 in 500 adults worldwide. HCM is characterized by myocyte hypertrophy resulting in thickening of the ventricular wall, myocyte disarray, interstitial and/or replacement fibrosis, decreased ventricular cavity volume and diastolic dysfunction. HCM is also the most common cause of sudden death in the young. A large proportion of patients diagnosed with HCM have mutations in sarcomeric proteins. However, it is unclear how these mutations lead to the cardiac phenotype, which is variable even in patients carrying the same causal mutation. Abnormalities in calcium cycling, oxidative stress, mitochondrial dysfunction and energetic deficiency have been described constituting the basis of therapies in experimental models of HCM and HCM patients. This review focuses on evidence supporting the role of cellular metabolism and mitochondria in HCM.
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