scholarly journals Targeting Mitochondrial Oxidative Stress in Heart Failure

2011 ◽  
Vol 58 (1) ◽  
pp. 83-86 ◽  
Author(s):  
Christoph Maack ◽  
Michael Böhm
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Mitochondrial Oxidative Stress

scholarly journals Mitochondrial Oxidative Stress Mediates Angiotensin II–Induced Cardiac Hypertrophy and Gαq Overexpression–Induced Heart Failure

2011 ◽  
Vol 108 (7) ◽  
pp. 837-846 ◽  
Author(s):  
Dao-Fu Dai ◽  
Simon C. Johnson ◽  
Jason J. Villarin ◽  
Michael T. Chin ◽  
Madeline Nieves-Cintrón ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Mitochondrial Oxidative Stress

scholarly journals Restore mitophagy is essential to prevent cardiac oxidative stress during hypertrophy

2021 ◽  
Author(s):  
Victoriane Peugnet ◽  
Maggy Chwastyniak ◽  
Steve Lancel ◽  
Laurent Bultot ◽  
Natacha Fourny ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Mitochondrial Biogenesis ◽  
Targeted Therapies ◽  
Superoxide Anion ◽  
Cardiomyocyte Hypertrophy ◽  
Mitochondrial Oxidative Stress ◽  
Mitochondrial Superoxide ◽  
The Impact

AbstractHeart failure, mostly associated with cardiac hypertrophy, is still a major cause of illness and death. Oxidative stress causes contractile failure and the accumulation of reactive oxygen species leads to mitochondrial dysfunction, associated with aging and heart failure, suggesting that mitochondria-targeted therapies could be effective in this context. The purpose of this work was to characterize how mitochondrial oxidative stress is involved in cardiac hypertrophy development and to determine if mitochondria-targeted therapies could improve cardiac phenotypes. We used neonatal and adult rat cardiomyocytes (NCMs and ACMs) hypertrophied by isoproterenol (Iso) to induce an increase of mitochondrial superoxide anion. Superoxide dismutase 2 activity and mitochondrial biogenesis were significantly decreased after 24h of Iso treatment. To counteract the mitochondrial oxidative stress induced by hypertrophy, we evaluated the impact of two different anti-oxidants, mitoquinone (MitoQ) and EUK 134. Both significantly decreased mitochondrial superoxide anion and hypertrophy in hypertrophied NCMs and ACMs. Conversely to EUK 134 which preserved cell functions, MitoQ impaired mitochondrial function by decreasing maximal mitochondrial respiration, mitochondrial membrane potential and mitophagy (particularly Parkin expression) and altering mitochondrial structure. The same decrease of Parkin was found in human cardiomyocytes but not in fibroblasts suggesting a cell specificity deleterious effect of MitoQ. Our data showed the importance of mitochondrial oxidative stress in the development of cardiomyocyte hypertrophy. Interestingly, we observed that targeting mitochondria by an anti-oxidant (MitoQ) impaired metabolism specifically in cardiomyocytes. Conversely, the SOD mimic (EUK 134) decreased both oxidative stress and cardiomyocyte hypertrophy and restored impaired cardiomyocyte metabolism and mitochondrial biogenesis.

Abstract 15796: Increased Cardiac Heme Levels Through Cardiac Overexpression of Delta-aminolevulinic Acid Synthase 2 (ALAS2) Lead to Exacerbated Ischemic Injury

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Konrad T Sawicki ◽  
Meng Shang ◽  
Rongxue Wu ◽  
Hsiang-Chun Chang ◽  
Arineh Khechaduri ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Cell Death ◽  
Transgenic Mice ◽  
Cardiac Function ◽  
Ischemic Cardiomyopathy ◽  
Aminolevulinic Acid ◽  
Causative Role ◽  
Mitochondrial Oxidative Stress ◽  
Coronary Ligation

Introduction: Heme is an essential iron-containing molecule for cardiovascular physiology, but in excess it may increase oxidative stress. Failing human hearts have increased heme levels, with upregulation of the rate-limiting enzyme in heme synthesis, δ-aminolevulinic acid synthase 2 (ALAS2), which is normally not expressed in cardiomyocytes. Hypothesis: We hypothesized that increased heme accumulation (through cardiac overexpression of ALAS2) leads to increased oxidative stress and cell death in the heart. Results: We first showed that ALAS2 and heme levels are increased in the hearts of mice subjected to coronary ligation. To determine the causative role of increased heme in the development of heart failure, we generated transgenic mice with cardiac-specific overexpression of ALAS2. While ALAS2 transgenic mice have normal cardiac function at baseline, their hearts display increased heme content, higher oxidative stress, exacerbated cell death, and worsened cardiac function after coronary ligation compared to non-transgenic littermates. We confirmed in cultured cardiomyoblasts that the increased oxidative stress and cell death by ALAS2 overexpression is mediated by increased heme accumulation. Furthermore, knockdown of ALAS2 in cultured cardiomyoblasts exposed to hypoxia reversed the increases in heme content and cell death. Administration of the mitochondrial antioxidant MitoTempo to ALAS2-overexpressing cardiomyoblasts normalized the elevated oxidative stress and cell death levels to baseline, indicating that the effects of increased ALAS2 and heme are through elevated mitochondrial oxidative stress. The clinical relevance of these findings was supported by the finding of increased ALAS2 induction and heme accumulation in failing human hearts from patients with ischemic cardiomyopathy compared to non-ischemic cardiomyopathy. Conclusions: Heme accumulation is detrimental to cardiac function under ischemic conditions, and reducing heme in the heart may be a novel approach for protection against the development of heart failure.

Mitochondrial Oxidative Stress, DNA Damage, and Heart Failure

2006 ◽  
Vol 8 (9-10) ◽  
pp. 1737-1744 ◽  
Author(s):  
Hiroyuki Tsutsui ◽  
Tomomi Ide ◽  
Shintaro Kinugawa
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Dna Damage ◽  
Mitochondrial Oxidative Stress

Sirtuin 4 contributes to heart failure development by increasing mitochondrial oxidative stress

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Koentges ◽  
E Khan ◽  
S Birkle ◽  
M Hoelscher ◽  
K Pfeil ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Cardiac Function ◽  
Funding Source ◽  
Lipid Peroxidation Product ◽  
German Research Foundation ◽  
Mitochondrial Oxidative Stress ◽  
Pronounced Increase ◽  
National Budget ◽  
Public Grant

Abstract   Sirtuin 4 (SIRT4) is a mitochondrial NAD+-dependent deacylase which inhibits the oxidation of glucose and fatty acids, and has been implicated in the regulation of oxidative stress. Given the importance of cardiac energy depletion and ROS during heart failure development, we aimed to define the role of SIRT4 in the development of heart failure. Mice with deletion (SIRT4−/−) or overexpression (SIRT4 TG) of SIRT4 were subjected to transverse aortic constriction (TAC) for 12 weeks or underwent sham procedures. Using echocardiography, ejection fraction (EF) was not different between SIRT4 TG and WT mice subjected to sham operations. In contrast, TAC induced a more pronounced decrease in EF (35% vs. 51%; p<0.05), and a more pronounced increase in LV endsystolic diameter (4.5mm vs. 3.6mm; p<0.05) and myocardial fibrosis (2.2-fold; p<0.05) in SIRT4 TG mice compared to WT mice. Myocardial levels of the lipid peroxidation product 4-hydroxynonenal were increased in WT mice following TAC and were synergistically increased in SIRT4 TG mice following TAC (+66% vs. WT TAC; p<0.05). Administration of the mitochondria-targeted antioxidant MitoQ normalized 4-hydroxynonenal levels, markedly attenuated the decline in EF and almost normalized endsystolic LV diameter in SIRT4 TG mice following TAC. Cardiac function and morphology were unaffected in SIRT4−/− mice during normal or increased workload conditions. Thus, while SIRT4 is not required to maintain cardiac function even in response to increased energy demands, increased expression of SIRT4 accelerates the development of heart failure following TAC, at least in part due to increased mitochondrial oxidative stress. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): German Research Foundation

scholarly journals Mitochondrial Oxidative Stress in Heart Failure

2000 ◽  
Vol 86 (2) ◽  
pp. 119-120 ◽  
Author(s):  
Douglas B. Sawyer ◽  
Wilson S. Colucci
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Mitochondrial Oxidative Stress
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