scholarly journals Nox4 Knockout Does Not Prevent Diaphragm Atrophy, Contractile Dysfunction, or Mitochondrial Maladaptation in the Early Phase Post-Myocardial Infarction in Mice

2021 ◽  
Vol 55 (4) ◽  
pp. 489-504
Keyword(s):  
Myocardial Infarction ◽  
Early Phase ◽  
Citrate Synthase ◽  
Force Transducer ◽  
Post Myocardial Infarction ◽  
Whole Body ◽  
Contractile Dysfunction ◽  
Cross Sectional ◽  
Diaphragm Atrophy

Background/Aims: Diaphragm dysfunction with increased reactive oxygen species (ROS) occurs within 72 hrs post-myocardial infarction (MI) in mice and may contribute to loss of inspiratory maximal pressure and endurance in patients. Methods: We used wild-type (WT) and whole-body Nox4 knockout (Nox4KO) mice to measure diaphragm bundle force in vitro with a force transducer, mitochondrial respiration in isolated fiber bundles with an O2 sensor, mitochondrial ROS by fluorescence, mRNA (RT-PCR) and protein (immunoblot), and fiber size by histology 72 hrs post-MI. Results: MI decreased diaphragm fiber cross-sectional area (CSA) (~15%, p = 0.015) and maximal specific force (10%, p = 0.005), and increased actin carbonylation (5-10%, p = 0.007) in both WT and Nox4KO. Interestingly, MI did not affect diaphragm mRNA abundance of MAFbx/atrogin-1 and MuRF-1 but Nox4KO decreased it by 20-50% (p < 0.01). Regarding the mitochondria, MI and Nox4KO decreased the protein abundance of citrate synthase and subunits of electron transport system (ETS) complexes and increased mitochondrial O2 flux (JO2) and H2O2 emission (JH2O2) normalized to citrate synthase. Mitochondrial electron leak (JH2O2/JO2) in the presence of ADP was lower in Nox4KO and not changed by MI. Conclusion: Our study shows that the early phase post-MI causes diaphragm atrophy, contractile dysfunction, sarcomeric actin oxidation, and decreases citrate synthase and subunits of mitochondrial ETS complexes. These factors are potential causes of loss of inspiratory muscle strength and endurance in patients, which likely contribute to the pathophysiology in the early phase post-MI. Whole-body Nox4KO did not prevent the diaphragm abnormalities induced 72 hrs post-MI, suggesting that systemic pharmacological inhibition of Nox4 will not benefit patients in the early phase post-MI.

Abstract 17357: Direct Cardiac Reprogramming Using Combinatorial Modified mRNA

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Keerat Kaur ◽  
Asharee Mahmoud ◽  
Hanna Girard ◽  
Ann Anu Kurian ◽  
Magdalena Zak ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Gene Delivery ◽  
High Efficiency ◽  
De Novo ◽  
Heart Function ◽  
Lineage Tracing ◽  
Dominant Negative ◽  
Post Myocardial Infarction ◽  
Transduction Efficiency

Introduction: Despite various clinical modalities, ischemic heart disease remains among the leading causes of mortality and morbidity worldwide. The elemental problem is the immense loss of cardiomyocytes (CMs) post-myocardial infarction (MI). Reprogramming non- cardiomyocytes (non-CMs) into cardiomyocyte (CM)-like cells in vivo is a promising strategy for cardiac regeneration: however, the traditional viral delivery method hampered its application into clinical settings due to low and erratic transduction efficiency. Methods: We used a modified mRNA (modRNA) gene delivery platform to deliver different stoichiometry of cardiac-reprogramming genes (Gata4, Mef2c, Tbx5 and Hand2) together with reprogramming helper genes (Dominant Negative (DN)-TGFβ, DN- Wnt8a and Acid ceramidase (AC)), named 7G, to induce direct cardiac reprogramming post myocardial infarction (MI). Results: Here, we identified 7G modRNA cocktail as an important regulator ofthe cardiac reprogramming. Cardiac transfection with 7G modRNA doubled cardiac reprogramming efficiency (57%) in comparison to Gata4, Mef2C and Tbx5 (GMT) alone (28%) in vitro . By inducing MI in our lineage tracing model, we showed that one-time delivery of the 7G-modRNA cocktail reprogrammed ~25% of the non-CMs in the scar area to CM- like cells. Furthermore, 7G modRNA treated mice showed significantly improved cardiac function, longer survival, reduced scar size and greater capillary density than control mice 28 days post-MI. We attributed the improvement in heart function post modRNA delivery of 7G or 7G with increased Hand2 ratio (7G-GMT Hx2) to significant upregulation of 15 key angiogenic factors without any signs of angioma or edema. Conclusions: 7G or 7G GMT HX2 modRNA cocktails boosts de novo CM-like cells and promotes cardiovascular regeneration post-MI. Thus, we highlight that this gene delivery approach not only has high efficiency but also high margin of safety for translation to clinics.

Abstract 56: Candesartan And Valsartan, Contrary To Irbesartan, Are Potent Biased Antagonists Of Adrenal (beta)arrestin-dependent, Angiotensin II Type 1 Receptor-induced Aldosterone Production And Improve Cardiac Function Post-myocardial Infarction

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Anastasios Lymperopoulos ◽  
Karlee Walklett ◽  
Samalia Dabul ◽  
Ashley Siryk ◽  
Emmanuel Sturchler ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Angiotensin Ii ◽  
Cardiac Function ◽  
G Protein ◽  
Plasma Aldosterone ◽  
Post Myocardial Infarction ◽  
Aldosterone Production

Introduction: The scaffolding protein βarrestin1 (βarr1) by the angiotensin II (AngII) type 1 receptor (AT 1 R) mediates AngII-induced aldosterone production in vitro and physiologically in vivo, thereby exacerbating heart failure (HF) progression post-myocardial infarction (MI). Herein, we sought to investigate the relative potency of various AT 1 R antagonist drugs (sartans) at inhibiting βarr vs. G protein activation and hence aldosterone production in vitro and in vivo. We also investigated the alterations in plasma aldosterone levels conferred by these agents and their impact on cardiac function of post-MI rats. Methods: For the in vitro tests, transfected CHO and adrenocortical H295R cells were used. For in vivo studies, post-MI rats overexpressing βarr1 in their adrenals received 7-day-long treatments with the drugs of interest. Results: Among the sartans tested, candesartan and valsartan were the most potent βarr activation and βarr-mediated aldosterone production inhibitors in vitro, as well as the most “biased” antagonists towards βarr vs. G-protein inhibition. Conversely, losartan and irbesartan were the least potent βarr inhibitors and the least “biased” antagonists towards βarr inhibition. These in vitro findings were corroborated in vivo, since candesartan and valsartan, contrary to irbesartan, caused significant plasma aldosterone reductions in post-MI rats. Accordingly, cardiac ejection fraction (EF) and contractility were significantly augmented in candesartan- and valsartan-treated rats (EF: 41.1±1% and 40±1% respectively, vs. 35±0.3% for saline-treated), but further deteriorated in irbesartan-treated post-MI rats (EF: 32±1%, n=7 rats/group). Conclusions: These findings provide important insights that might aid pharmacotherapeutic decisions (i.e. individual agent selections) involving this commonly prescribed cardiovascular drug class (sartans).

scholarly journals Quantification and MRI Validation of Regional Contractile Dysfunction in Mice Post Myocardial Infarction Using High Resolution Ultrasound

2007 ◽  
Vol 33 (6) ◽  
pp. 894-904 ◽  
Author(s):  
Yinbo Li ◽  
Christopher D. Garson ◽  
Yaqin Xu ◽  
Ronald J. Beyers ◽  
Frederick H. Epstein ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
High Resolution ◽  
Post Myocardial Infarction ◽  
Contractile Dysfunction

scholarly journals Sexual Knowledge in Post-Myocardial Infarction Patients: A Cross-Sectional Study

Cureus ◽  
2020 ◽  
Author(s):  
Rida Farhan ◽  
Rabail Yousuf ◽  
Syeda Namayah Fatima Hussain ◽  
Maaz Khan ◽  
Zara Bilal ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cross Sectional Study ◽  
Post Myocardial Infarction ◽  
Sexual Knowledge ◽  
Sectional Study ◽  
Cross Sectional

scholarly journals Chamber Specification During Direct Cardiac Reprogramming

2021 ◽  
Author(s):  
Zhentao Zhang ◽  
Jesse Villalpando ◽  
Wenhui Zhang ◽  
Young-Jae Nam
Keyword(s):  
Myocardial Infarction ◽  
Transcription Factors ◽  
Post Myocardial Infarction ◽  
Heart Regeneration ◽  
Proof Of Concept ◽  
Major Fraction ◽  
Regenerative Approach ◽  
Inherent Advantage

Abstract Forced expression of core cardiogenic transcription factors can directly reprogram fibroblasts to induced cardiomyocyte-like cells (iCMs) in vitro and in vivo. This cardiac reprogramming approach provides a proof of concept for induced heart regeneration by converting a fibroblast fate to a cardiomyocyte fate. However, it remains elusive whether chamber-specific cardiomyocytes can be generated by cardiac reprogramming. Therefore, we assessed the ability of the cardiac reprogramming approach for chamber specification in vitro and in vivo. We found that in vivo cardiac reprogramming post-myocardial infarction exclusively generates ventricular-like iCMs, while a major fraction of iCMs generated in vitro fail to determine their chamber identities. Our results indicate that in vivo cardiac reprogramming may have an inherent advantage of generating chamber-matched new cardiomyocytes as a potential heart regenerative approach.

scholarly journals Factors Associated with Perceived Life Chaos among Post-Myocardial Infarction Survivors in a Malaysian Cardiac Care Facility

Medicina ◽  
2018 ◽  
Vol 54 (5) ◽  
pp. 79
Author(s):  
Kurubaran Ganasegeran ◽  
Abdul Rashid
Keyword(s):  
Myocardial Infarction ◽  
Care Facility ◽  
Cross Sectional Study ◽  
Post Myocardial Infarction ◽  
Cross Sectional ◽  
Psychological Stressors ◽  
Younger Age ◽  
Social Support Scale ◽  
Life Threatening ◽  
Self Administered Questionnaire

Background and objectives: Survivors of chronic life-threatening conditions like myocardial infarction (MI) are often confronted with multiple physical and psychological stressors as a consequence of elevated demands of lifestyle adjustments and modifications. Such stressors, collectively known as “life chaos”, cause disruption to one’s lifestyle equilibrium of having organized, calm, and regular routines. The objective of the current study was to determine the level of life chaos and its associated correlates among post-myocardial infarction (post-MI) survivors in Malaysia. Materials and Methods: An analytical cross-sectional study was conducted among 242 post-MI survivors in a Malaysian cardiac health facility from July to September 2016. A self-administered questionnaire in Malay that consisted of items on socio-demographics, health attributes, validated OSLO-3 Social Support Scale (OSS-3), and the Modified Confusion, Hubbub, and Order Scale (CHAOS-6) was utilized in this study. Descriptive, bivariate, and multivariate analyses were conducted. Results: The sample constituted of 208 (86%) men and 34 (14%) women. The average age was 55 years (SD = 11), and the age ranged between 24 and 96 years. Overall, 128 (52.9%) of the total post-MI survivors had highly chaotic lives. In multivariate analysis, younger age, lower household income, perceived financial insecurity, poor health status, and multiple comorbidities were related to the high chaos score, and these associations were statistically significant (p < 0.05). Conclusions: Highly chaotic lifestyles were prevalent in post-MI survivors. Demographic, health attributes, and socio-economic factors were important correlates of life chaos.

Coping styles among post-myocardial infarction patients with depressive symptoms

2011 ◽  
Vol 26 (S2) ◽  
pp. 371-371
Author(s):  
R. Bagherian ◽  
M. Maroufi ◽  
F. Said Zare ◽  
P. Niksirat
Keyword(s):  
Myocardial Infarction ◽  
Depressive Symptoms ◽  
Attribution Theory ◽  
Coping Style ◽  
Coping Styles ◽  
Depression Scale ◽  
Cross Sectional Study ◽  
Post Myocardial Infarction ◽  
Cross Sectional ◽  
Significant Difference

ObjectiveAlthough the adverse impact of post-myocardial infarction (MI) depressive symptoms on prognosis of heart disease has been found, the link between coping strategies and post-MI depressive symptoms has yet been unclear. The aim of this study was to determine the relationship between coping styles and post-MI depressive symptoms.MethodsIn a cross sectional study one hundred consecutive patients following MI admitted to the CCU wards of hospitals in Isfahan were selected in respect of inclusive and exclusive criteria. The patients completed Jalowiec Coping questionnaire, Hospital Anxiety and Depression Scale and Norbeck Social Support questionnaire. Then the data was analysed by using MANCOVA and Covariance.ResultsThe findings indicated that 31% were the MI patients with depressive symptoms. The results of MANCOVA showed significant difference between two groups with and without depressive symptoms in coping styles (F = 2/185, P = 0.036). Also, the results of covariance indicated significant differences in coping styles including optimistic coping style (F = 3.754, P = 0.05) and supportant coping style (F = 6.66, P = 0.019). However, there was no significant difference in other coping styles between two groups.ConclusionThe low tendency toward optimistic and supportant coping styles seem to play an important role in experiencing depressive symptoms among post-MI patients. Lock of optimism in dealing with life events is one of equivalents to hopelessness in Attribution theory explaining depression. Investigation of relationship between religious beliefs and effective coping styles would be worthwhile.

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