Review Article
Volume 7 Issue 2 - 2020
A New Look at the Causes of Heart Failure at Old Age
Alexander V Panov*
Institute of Molecular Biology and Biophysics, Academy of Sciences of Russia, Novosibirsk, Russian Federation
*Corresponding Author: Alexander V Panov, Institute of Molecular Biology and Biophysics, Academy of Sciences of Russia, Novosibirsk, Russian Federation.
Received: December 23, 2019; Published: January 20, 2020




Abstract

Most of the time, researchers in different fields of Science develop certain ideas or conceptions For some time these conceptions exist separately, but from time to time something happens, and these separate ideas, like small parts of a complex puzzle, begin to fell into much larger Scientific picture. In this brief review we make an attempt to bind together recently published new data regarding age-associated mutations of mtDNA, roles of mitochondrial phospholipids cardiolipin (CL) and phosphatidylethanolamine (PEA) in mitochondrial functions, oxidation of fatty acids in the heart’s energy metabolism and in oxidative stress, for better understanding of the mechanisms of aging and age-associated heart diseases. We came to conclusion that increased β-oxidation of fatty acids in people at the ages after 50 - 60 accelerates production of perhydroxyl radical, which activates in the heart the nonenzymatic autoxidation of CL and PEA and polyunsaturated fatty acids (PUFA). Autooxidation of PUFA produces a racemic mixture of hundreds of toxic molecules that gradually make mitochondria dysfunctional. Due to a large redundancy of mitochondrial enzymes these widely variable harms remain unnoticed for a long time. We conclude that not mutated mtDNA, but slowly accumulating dysfunctions cause wear and tear of the heart.

Keywords: mtDNA; Cardiolipin (CL); Phosphatidylethanolamine (PEA); Polyunsaturated Fatty Acids (PUFA)

References

  1. Stanley WC and Chandler MP. “Energy metabolism in the normal and failing heart: potential for therapeutic interventions”. Heart Failure Reviews 7.2 (2002):115-130.
  2. Panov AV. “Synergistic oxidation of fatty acids, glucose and amino acids metabolites by isolated rat heart mitochondria”. EC Cardiology 5.4 (2018).
  3. Panov AV and Dikalov SI. “The mitochondrial metabolism and the Age-associated cardiovascular diseases”. EC Cardiology 5.11 (2018): 750-769.
  4. Gonzalez-Freire M., et al. "Reconsidering the Role of Mitochondria in Aging”. Journals of Gerontology. Series A: Biological Sciences and Medical Sciences 70 (2015): 1334-1342.
  5. Carr MC. “The emergence of the metabolic syndrome with menopause”. The Journal of Clinical Endocrinology and Metabolism 88.6 (2003): 2404-2411.
  6. Grundy SM. "Metabolic syndrome: a multiplex cardiovascular risk factor”. The Journal of Clinical Endocrinology and Metabolism 92.2 (2007): 399-404.
  7. Grundy SM., et al. "Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement”. Circulation 112.17 (2005): 2735-2752.
  8. Harman D. “The aging process”. Proceedings of the National Academy of Sciences of the United States of America 78 (1981): 7124-7128. 
  9. Harman D. "Free radical theory of aging: an update: increasing the functional life span”. Annals of the New York Academy of Sciences 1067 (2006): 10-21.
  10. Beckman KB and BN Ames. "The free radical theory of aging matures”. Physiological Reviews 78.2 (1998): 547-581.
  11. Ryzhkova AI., et al. "Mitochondrial diseases caused by mtDNA mutations: a mini-review”. Therapeutics and Clinical Risk Management 14 (2018): 1933-1942.
  12. Volobueva A., et al. “Changes in Mitochondrial Genome Associated with Predisposition to Atherosclerosis and Related Disease”. Biomolecules 9 (2019): 377. 
  13. Pinto M CT., et al. “Mechanisms linking mtDNA damage and aging”. Free Radical Biology and Medicine 85 (2015): 250-258.
  14. Szczepanowska K and Trifunovic A. “Origins of mtDNA mutations in ageing”. Essays in Biochemistry 61.3 (2017): 325-337. 
  15. DeBalsi KL., et al. "Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases”. Ageing Research Reviews 33 (2017): 89-104.
  16. Chocron ES., et al. “Cause or casualty: The role of mitochondrial DNA in aging and ageassociated disease”. Biochimica et Biophysica Acta - Molecular Basis of Disease 1865 (2019): 285-297.
  17. Paradies G., et al. "Role of cardiolipin peroxidation and Ca2+ in mitochondrial dysfunction and disease”. Cell Calcium 45.6 (2009): 643-650.
  18. Paradies G., et al. "Mitochondrial dysfunction in brain aging: role of oxidative stress and cardiolipin”. Neurochemistry International 58.4 (2011): 447-457.
  19. Brame CJ., et al. “Modification of proteins by isoketal-containing oxidized phospholipids”. The Journal of Biological Chemistry 279 (2004): 13447-13451.
  20. Montine TJ and Morrow JD. “Fatty acid oxidation in the pathogenesis of Alzheimer's disease”. The American Journal of Pathology 166 (2005): 1283-1285.
  21. Horvath SE and G Daum. “Lipids of mitochondria”. Progress in Lipid Research 52 (2013): 590-614.
  22. Houtkooper RH and FM Vaz. “Cardiolipin, the heart of mitochondrial metabolism”. Cellular and Molecular Life Sciences 65 (2008): 2493-2506.
  23. Van Meer G and AI de Kroon. “Lipid map of the mammalian cell”. Journal of Cell Science 124 (2011): 5-8.
  24. Jouhet J. “Importance of the hexagonal lipid phase in biological membrane organization”. Frontiers in Plant Science 4 (2013): 494.
  25. Roberts LJ., et al. “Formation of isoprostane-like compounds (neuroprostanes) in vivo from docosahexaenoic acid”. Journal of Biological Chemistry 273 (1988): 13605-13612.
  26. Brame CJ., et al. “Modification of proteins by isoketal-containing oxidized phospholipids”. Journal of Biological Chemistry 279 (2004): 13447-13451.
  27. Musiek ES., et al. “Recent advances in the biochemistry and clinical relevance of the isoprostane pathway”. Lipids 40 (2005): 987-994.
  28. Montine TJ and Morrow JD. “Fatty acid oxidation in the pathogenesis of Alzheimer's disease”. The American Journal of Pathology 166 (2005): 1283-1285.
  29. Panov A. “Perhydroxyl radical (HO2) as inducer of the isoprostane lipid peroxidation in mitochondria”. Journal of Molecular Biology 52 (2018): 295-305. 
  30. Haines TH and NA Dencher. “Cardiolipin: a proton trap for oxidative phosphorylation”. FEBS Letters 528 (2002): 35-39.
  31. Jouhet J. “Importance of the hexagonal lipid phase in biological membrane organization”. Frontiers in Plant Science 4 (2013): 494.
  32. Arnarez C., et al. “Identification of cardiolipin binding sites on cytochrome c oxidase at the entrance of proton channels”. Scientific Reports 3 (2013): 1263.
  33. Sathappa M and NN Alder. “The ionization properties of cardiolipin and its variants in model bilayers”. Biochimica et Biophysica Acta 1858 (2016): 1362-1372. 
  34. Bielski BHJ. “Reevaluation of the spectral and kinetic properties of HO2 and O2- free radicals”. Photochemistry and Photobiology 28 (1978): 645-649.
  35. Dikalov SI and AE Dikalova. "Crosstalk Between Mitochondrial Hyperacetylation and Oxidative Stress in Vascular Dysfunction and Hypertension”. Antioxidants and Redox Signaling 31.10 (2019): 710-721.
  36. Dikalova AE., et al. “Mitochondrial Deacetylase Sirt3 Reduces Vascular Dysfunction and Hypertension While Sirt3 Depletion in Essential Hypertension Is Linked to Vascular Inflammation and Oxidative Stress”. Circulation Research (2019). 
  37. Academic Press Dictionary of Science and Technology. Christopher Morris, Ed., Academic Press, Inc. (1992).
  38. Anderson EJ., et al. “Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans”. Journal of Clinical Investigation 119 (2009): 573-581.
  39. Carr MC. “The emergence of the metabolic syndrome with menopause”. The Journal of Clinical Endocrinology and Metabolism 88 (2003): 2404-2411.
  40. Anderson AP., et al. “Oxidative damage diminishes mitochondrial DNA polymerase replication fidelity”. Nucleic Acids Research (2019). 
Citation: Alexander V Panov. “A New Look at the Causes of Heart Failure at Old Age”. EC Cardiology 7.2 (2020): 01-07.

PubMed Indexed Article


EC Pharmacology and Toxicology
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.

PMID: 31143884 [PubMed]

PMCID: PMC6536005


EC Pharmacology and Toxicology
Alzheimer's Pathogenesis, Metal-Mediated Redox Stress, and Potential Nanotheranostics.

PMID: 31565701 [PubMed]

PMCID: PMC6764777


EC Neurology
Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer's Disease and Vascular Dementia: a Retrospective Study.

PMID: 27747317 [PubMed]

PMCID: PMC5065347


EC Pharmacology and Toxicology
Will Blockchain Technology Transform Healthcare and Biomedical Sciences?

PMID: 31460519 [PubMed]

PMCID: PMC6711478


EC Pharmacology and Toxicology
Is it a Prime Time for AI-powered Virtual Drug Screening?

PMID: 30215059 [PubMed]

PMCID: PMC6133253


EC Psychology and Psychiatry
Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

PMID: 30417173 [PubMed]

PMCID: PMC6226033


EC Anaesthesia
Arrest Under Anesthesia - What was the Culprit? A Case Report.

PMID: 30264037 [PubMed]

PMCID: PMC6155992


EC Orthopaedics
Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct Skeletal Attachment.

PMID: 30198026 [PubMed]

PMCID: PMC6124505


EC Pulmonology and Respiratory Medicine
Prevalence and factors associated with self-reported chronic obstructive pulmonary disease among adults aged 40-79: the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PMID: 30294723 [PubMed]

PMCID: PMC6169793


EC Dental Science
Important Dental Fiber-Reinforced Composite Molding Compound Breakthroughs

PMID: 29285526 [PubMed]

PMCID: PMC5743211


EC Microbiology
Prevalence of Intestinal Parasites Among HIV Infected and HIV Uninfected Patients Treated at the 1o De Maio Health Centre in Maputo, Mozambique

PMID: 29911204 [PubMed]

PMCID: PMC5999047


EC Microbiology
Macrophages and the Viral Dissemination Super Highway

PMID: 26949751 [PubMed]

PMCID: PMC4774560


EC Microbiology
The Microbiome, Antibiotics, and Health of the Pediatric Population.

PMID: 27390782 [PubMed]

PMCID: PMC4933318


EC Microbiology
Reactive Oxygen Species in HIV Infection

PMID: 28580453 [PubMed]

PMCID: PMC5450819


EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840


EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344


EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476


EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658


EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489


EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278


EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108


EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571


EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333


EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883


EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001


EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937


EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723


EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726


EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603


EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646


EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616


EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290


EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226


EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812


EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268


News and Events


July Issue Release

We always feel pleasure to share our updates with you all. Here, notifying you that we have successfully released the July issue of respective journals and the latest articles can be viewed on the current issue pages.

Submission Deadline for upcoming Issue

Ecronicon delightfully welcomes all the authors around the globe for effective collaboration with an article submission for the upcoming issue of respective journals. Submissions are accepted on/before August 09, 2021.

Certificate of Publication

Ecronicon honors with a "Publication Certificate" to the corresponding author by including the names of co-authors as a token of appreciation for publishing the work with our respective journals.

Best Article of the Issue

Editors of respective journals will always be very much interested in electing one Best Article after each issue release. The authors of the selected article will be honored with a "Best Article of the Issue" certificate.

Certifying for Review

Ecronicon certifies the Editors for their first review done towards the assigned article of the respective journals.

Latest Articles

The latest articles will be updated immediately on the articles in press page of the respective journals.

Immediate Assistance

The prime motto of this team is to clarify all the queries without any delay or hesitation to avoid the inconvenience. For immediate assistance on your queries please don't hesitate to drop an email to editor@ecronicon.uk