What role does the stress response have in congestive heart failure?

Badreddin, Ahmed; Youssef, Fady; Attia, Hamdy; Hafez, Mohamed; Khairallah, Ahmed; Johar, Dina; Bernstein, Larry

doi:10.1002/jcp.26003

Cited by 12 publications

(5 citation statements)

References 51 publications

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“…Accumulating evidences suggest a critical role of ER stress in development of cardiac diseases, thus the modulation of ER stress responses is an attractive therapeutic strategy to intervene cardiovascular and heart diseases 2,31,32 . In this study, we demonstrate the importance of PRMT1 in suppression of ER stress.…”

Section: Discussionmentioning

confidence: 99%

PRMT1 suppresses ATF4-mediated endoplasmic reticulum response in cardiomyocytes

Jeong

Ahn

et al. 2019

Cell Death Dis

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Endoplasmic reticulum (ER) stress signaling plays a critical role in the control of cell survival or death. Persistent ER stress activates proapoptotic pathway involving the ATF4/CHOP axis. Although accumulating evidences support its important contribution to cardiovascular diseases, but its mechanism is not well characterized. Here, we demonstrate a critical role for PRMT1 in the control of ER stress in cardiomyocytes. The inhibition of PRMT1 augments tunicamycin (TN)-triggered ER stress response in cardiomyocytes while PRMT1 overexpression attenuates it. Consistently, PRMT1 null hearts show exacerbated ER stress and cell death in response to TN treatment. Interestingly, ATF4 depletion attenuates the ER stress response induced by PRMT1 inhibition. The methylation-deficient mutant of ATF4 with the switch of arginine 239 to lysine exacerbates ER stress accompanied by enhanced levels of proapoptotic cleaved Caspase3 and phosphorylated-γH2AX in response to TN. The mechanistic study shows that PRMT1 modulates the protein stability of ATF4 through methylation. Taken together, our data suggest that ATF4 methylation on arginine 239 by PRMT1 is a novel regulatory mechanism for protection of cardiomyocytes from ER stress-induced cell death.

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Section: Discussionmentioning

confidence: 99%

PRMT1 suppresses ATF4-mediated endoplasmic reticulum response in cardiomyocytes

Jeong

Ahn

et al. 2019

Cell Death Dis

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“…Therefore, in response to stimuli such as trauma, infection, and hypoxia, their cardiovascular functions are more easily and greatly impaired, leading to a significantly higher likelihood of acute deterioration of their cardiovascular system [ 21 ], and resulting in cardiac and pulmonary dysfunction, which can be complicated by acute heart failure [ 22 ]. Furthermore, systemic metabolic disorders and depletion during post-traumatic stress can further impair cardiac function and increase the likelihood of acute cardiac complications [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Risk factors for short-term mortality in elderly hip fracture patients with complicated heart failure in the ICU: A MIMIC-IV database analysis using nomogram

Lu,

Chen,

Guo

et al. 2023

J Orthop Surg Res

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Background Hip fracture is a prevalent and hazardous injury among the elderly population that often results in intensive care unit (ICU) admission due to various complications, despite advanced medical science. One common complication experienced in the ICU by elderly hip fracture patients is heart failure, which significantly impacts short-term survival rates. Currently, there is a deficit of adequate predictive models to forecast the short-term risk of death following heart failure for elderly hip fracture patients in the ICU. This study aims to identify independent risk factors for all-cause mortality within 30 days for elderly patients with hip fractures and heart failure while in the ICU in order to develop a predictive model. Method A total of 641 elderly patients with hip fractures combined with heart failure were recruited from the Medical Information Mart for Intensive Care IV dataset and randomized to the training and validation sets. The primary outcome was all-cause mortality within 30 days. The least absolute shrinkage and selection operator regression was used to reduce data dimensionality and select features. Multivariate logistic regression was used to build predictive models. Consistency index (C-index), receiver operating characteristic curve, and decision curve analysis (DCA) were used to measure the predictive performance of the nomogram. Result Our results showed that these variables including MCH, MCV, INR, monocyte percentage, neutrophils percentage, creatinine, and combined sepsis were independent factors for death within 30 days in elderly patients with hip fracture combined with heart failure in the ICU. The C-index was 0.869 (95% CI 0.823–0.916) and 0.824 (95% CI 0.749–0.900) for the training and validation sets, respectively. The results of the area under the curve and decision curve analysis (DCA) confirmed that the nomogram performed well in predicting elderly patients with hip fractures combined with heart failure in the ICU. Conclusion We developed a new nomogram model for predicting 30-day all-cause mortality in elderly patients with hip fractures combined with heart failure in the ICU, which could be a valid and useful clinical tool for clinicians for targeted treatment and prognosis prediction.

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“…As a consequence, the structure and function of the remaining myocardium are disrupted, eventually leading to HF (12). The apoptosis of cardiomyocytes often occurs throughout the process of heart disease, and improvement of cardiac function largely relies on the surviving cardiomyocytes (21,22). It has been demonstrated that oxidative stress is the main cause of hypoxic and ischemic heart diseases (23,24).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑138‑5p drives the progression of heart failure via inhibiting sirtuin 1 signaling

2021

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The present study aimed to investigate the regulatory effects of microRNA-138-5p (miR-138-5p) and sirtuin 1 (SIRT1) on the progression of heart failure (HF). The binding association between miR-138-5p and SIRT1 was assessed by the dual-luciferase reporter assay. By conducting reverse transcription-quantitative polymerase chain reaction and Western blotting, relative levels of SIRT1 and p53 regulated by miR-138-5p were detected. In vitro HF models were generated by hydrogen peroxide (H 2 O 2 ) induction in AC-16 and human cardiomyocyte (HCM) cells, followed by detection of the regulatory effects of SIRT1 on cell apoptosis and p53 expression. MiR-138-5p was negatively correlated with the SIRT1 level in cardiomyocytes. By recognizing and specifically targeting SIRT1 3′-untranslated region (3′-UTR), miR-138-5p decreased the translational level of SIRT1 and inhibited its enzyme activity, thereby decreasing the deacetylation level of p53. Through downregulating SIRT1 and activating p53 signaling, miR-138-5p induced apoptosis in H 2 O 2 -induced AC-16 and HCM cells. By contrast, knockdown of miR-138-5p in the in vitro HF models significantly protected the cardiomyocytes. SIRT1 contributed toward alleviate HF by inhibiting cardiomyocyte apoptosis via enhancing the deacetylation level of p53. MiR-138-5p decreases the enzyme activity of SIRT1 by specifically targeting its 3′-UTR and activates p53 signaling, followed by triggering cardiomyocyte apoptosis during the process of HF. It is considered that miR-138-5p and SIRT1 may be potential diagnostic biomarkers and therapeutic targets for HF.

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What role does the stress response have in congestive heart failure?

Cited by 12 publications

References 51 publications

PRMT1 suppresses ATF4-mediated endoplasmic reticulum response in cardiomyocytes

PRMT1 suppresses ATF4-mediated endoplasmic reticulum response in cardiomyocytes

Risk factors for short-term mortality in elderly hip fracture patients with complicated heart failure in the ICU: A MIMIC-IV database analysis using nomogram

MicroRNA‑138‑5p drives the progression of heart failure via inhibiting sirtuin 1 signaling

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