ArticleEuropean heart journal2011
Cation dyshomeostasis and cardiomyocyte necrosis: the Fleckenstein hypothesis revisited.
Article in European heart journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 47 citations in OpenAlex.
- Emerging Roles of Dystroglycan in Cardiac Remodeling, Fibrosis, and Heart Failure.International journal of molecular sciences · 2026Review
- Mitochondrial Transport Proteins in Cardiovascular Diseases: Metabolic Gatekeepers, Pathogenic Mediators and Therapeutic Targets.International journal of molecular sciences · 2025Review
- Article
- Takotsubo Syndrome: The Secret Crosstalk between Heart and Brain.Reviews in cardiovascular medicine · 2023Review
- Hypocalcemia as a cause of reversible heart failure: A case report and review of the literature.Annals of medicine and surgery (2012) · 2022Article
- Exercise triggers CAPN1-mediated AIF truncation, inducing myocyte cell death in arrhythmogenic cardiomyopathy.Science translational medicine · 2021Article
- The molecular mechanisms associated with the physiological responses to inflammation and oxidative stress in cardiovascular diseases.Biophysical reviews · 2020Review
- Fleckenstein's hypothesis revisited: excessive myocardial calcification after prolonged high dose catecholamine treatment: a case report.European heart journal. Case reports · 2018Article
- Effects of teriparatide on morphology of aortic calcification in aged hyperlipidemic mice.American journal of physiology. Heart and circulatory physiology · 2018Article
- Article
- Cardiovascular Mitochondrial Dysfunction Induced by Cocaine: Biomarkers and Possible Beneficial Effects of Modulators of Oxidative Stress.Oxidative medicine and cellular longevity · 2017Review
- Cardiovascular and Hepatic Toxicity of Cocaine: Potential Beneficial Effects of Modulators of Oxidative Stress.Oxidative medicine and cellular longevity · 2016Review
- Clinical and echocardiographic correlates of serum copper and zinc in acute and chronic heart failure.Clinical research in cardiology : official journal of the German Cardiac Society · 2014Article
- Pathophysiological mechanisms of catecholamine and cocaine-mediated cardiotoxicity.Heart failure reviews · 2014Review
- Zinc and the prooxidant heart failure phenotype.Journal of cardiovascular pharmacology · 2014Review
- Primary hypoparathyroidism presenting with heart failure and ventricular fibrillation.Oxford medical case reports · 2014Article
- β1-Adrenergic receptor signaling activates the epithelial calcium channel, transient receptor potential vanilloid type 5 (TRPV5), via the protein kinase A pathway.The Journal of biological chemistry · 2014Article
- Phosphoproteome mapping of cardiomyocyte mitochondria in a rat model of heart failure.Molecular and cellular biochemistry · 2014Article
- Takotsubo cardiomyopathy a short review.Current cardiology reviews · 2013Review
- Mineralocorticoid receptor antagonism confers cardioprotection in heart failure.Current heart failure reports · 2013Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
An ongoing loss of cardiomyocytes to apoptotic and necrotic cell death pathways contributes to the progressive nature of heart failure. The pathophysiological origins of necrotic cell loss relate to the neurohormonal activation that accompanies acute and chronic stressor states and which includes effector hormones of the adrenergic nervous system. Fifty years ago, Albrecht Fleckenstein and coworkers hypothesized the hyperadrenergic state, which accompanies such stressors, causes cardiomyocyte necrosis based on catecholamine-initiated excessive intracellular Ca(2+) accumulation (EICA), and mitochondrial Ca(2+) overloading in particular, in which the ensuing dysfunction and structural degeneration of these organelles leads to necrosis. In recent years, two downstream factors have been identified which, together with EICA, constitute a signal-transducer-effector pathway: (i) mitochondria-based induction of oxidative stress, in which the rate of reactive oxygen metabolite generation exceeds their rate of detoxification by endogenous antioxidant defences; and (ii) the opening of the mitochondrial inner membrane permeability transition pore (mPTP) followed by organellar swelling and degeneration. The pathogenesis of stress-related cardiomyopathy syndromes is likely related to this pathway. Other factors which can account for cytotoxicity in stressor states include: hypokalaemia; ionized hypocalcaemia and hypomagnesaemia with resultant elevations in parathyroid hormone serving as a potent mediator of EICA; and hypozincaemia with hyposelenaemia, which compromise antioxidant defences. Herein, we revisit the Fleckenstein hypothesis of EICA in leading to cardiomyocyte necrosis and the central role played by mitochondria.
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