Subacute ghrelin administration inhibits apoptosis and improves ultrastructural abnormalities in remote myocardium post-myocardial infarction

Eid, Refaat A.; Zaki, M. J.; Al‐Shraim, Mubarak; Eleawa, Samy M; El‐kott, Attalla F.; Al‐Hashem, Fahaid; Eldeen, Muhammad Alaa; Hoja, Ibrahim; Aldera, Hussain; Alkhateeb, Mahmoud

doi:10.1016/j.biopha.2018.03.010

Cited by 14 publications

(8 citation statements)

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“…A growing number of literature have reported the cardioprotective effects of ghrelin against MI [24][25][26], suggesting ghrelin as a promising therapeutic agent for MI. During MI, the serum ghrelin levels are decreased and the decreases are correlated with cardiac function [27].…”

Section: Discussionmentioning

confidence: 99%

Pretreatment of ghrelin protects H9c2 cells against hypoxia/reoxygenation-induced cell death via PI3K/AKT and AMPK pathways

Chen

Wang

Zhang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Ghrelin has been widely recognized as a key peptide in the cardiovascular system. This study detected the potential of ghrelin in MI management and tried to decode one of the possible underlying mechanisms. H9c2 cells were pretreated with ghrelin and were subjected to hypoxia/reoxygenation (H/R). CCK-8, flow cytometry, Western blot and LDH analysis were conducted to assess the changes in cell survival. LY294002 and Compound C were used to treat H9c2 cells for blocking PI3K/AKT and AMPK pathways, respectively. Ghrelin expression in H9c2 cells was suppressed by siRNA-mediated silencing to see the effects of endogenous ghrelin. We found that, following H/R, H9c2 cells viability was decreased, CyclinD1 and CDK4 were down-regulated, apoptosis was induced, the release of LDH was enhanced, and the expression levels of Cox-2 and iNOS were up-regulated. Ghrelin protected H9c2 cells against H/R induced these alterations. Besides, ghrelin activated PI3K/AKT and AMPK pathways even in H/Rstimulated cells. The protective effects of ghrelin against H/R-induced cell damage were all attenuated by the addition of LY294002 or Compound C. Moreover, endogenous inhibition of ghrelin significantly induced cell death of H9c2 cells. In conclusion, this study demonstrated that ghrelin pretreatment protected H9c2 cells against H/R-induced cell damage, possibly via PI3K/AKT and AMPK pathways. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 99%

Pretreatment of ghrelin protects H9c2 cells against hypoxia/reoxygenation-induced cell death via PI3K/AKT and AMPK pathways

Chen

Wang

Zhang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…One day after the last treatment, all animals were fasted for 12 hr and anesthetized with an i.p bolus of pentobarbital sodium (50 mg/kg) rats. Cardiac hemodynamic was recorded in each rat as previously described in our labs using a PowerLab data acquisition system (Version 8, ML780 PowerLab/8channels; ADInstruments) (Eid et al, ). The parameters that were derived from the recording the pressure signal were LV end systolic/diastolic pressure (LVEDP & LVSP, respectively) and the maximal/minimal change in LV pressure (LVdP/dtmax & LVdP/dtmin, respectively).…”

Section: Methodsmentioning

confidence: 99%

“…Collagen deposition in the frozen tissue transverse sections of LVs (5 µm thick) prepared from all rats was determined by a Masson's trichrome staining kit (Sigma) and all photos were photographed at a magnification of 200×. The processing of tissues and the procedure of electron microscopy study for all samples has been described in more details in our previous studies (Eid et al, ).…”

Section: Methodsmentioning

confidence: 99%

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A high‐fat diet rich in corn oil induces cardiac fibrosis in rats by activating JAK2/STAT3 and subsequent activation of ANG II/TGF‐1β/Smad3 pathway: The role of ROS and IL‐6 trans‐signaling

et al. 2019

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This study compared the effect of low‐fat diet (LFD) and high‐fat diet rich in corn oil (HFD‐CO) on left ventricular (LV) fibrosis in rats and examined their effect of angiotensin II (ANG II), JAK/STAT, and TGF‐1β/smad3 pathways. As compared to LFD which didn't affect any of the measured parameters, HFD‐CO‐induced type 2 diabetes phenotype and increased LV collagen synthesis. Mechanistically, it increased LV levels of ROS, ANG II, ACE, IL‐6, s‐IL‐6Rα, TGF‐β1, Smad‐3, and activities of JAK1/2 and STAT1/3. AG490, a JAK2 inhibitor, partially ameliorated these effect while Losartan, an AT1 inhibitor completely abolished collagen synthesis. However, with both treatments, levels of ANG II, IL‐6, and s‐IL‐6Rα, and activity of JAK1/STAT3 remained high, all of which were normalized by co‐administration of NAC or IL‐6 neutralizing antibody. In conclusion: HFD‐CO enhances LV collage synthesis by activation of JAK1/STAT3/ANG II/TGF‐1β/smad3 pathway. Practical applications We report that chronic consumption of a high‐fat diet rich in corn oil (HFD‐CO) induces diabetes mellitus phenotype 2 associated with left ventricular (LV) cardiac fibrosis in rats. The findings of this study show that HFD‐CO, and through the increasing generation of ROS and IL‐6 levels and shedding, could activate LV JAK1/2‐STAT1/3 and renin‐angiotensin system (RAS) signaling pathways, thus creating a positive feedback between the two which ultimately leads to activation of TGF‐1β/Smad3 fibrotic pathway. Herein, we also report a beneficial effect of the antioxidant, NAC, or IL‐6 neutralizing antibody in preventing such adverse effects of such HFD‐CO. However, this presents a warning message to the current sudden increase in idiopathic cardiac disorders, especially with the big shift in our diets toward n‐6 PUFA.

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“…Considering RM as a potential target for treatment strategies, several studies have demonstrated the beneficiary effects of therapeutic approaches, for example inducing a reduced heart rate, [22], anti-apoptotic effects in RM [23] or remodeling prevention via an angiotensin-AT1receptor-dependent mechanism [24]. Further explorations of RM strain characteristics and their features as targets of pharmacological treatment are necessary in future studies.…”

Section: Discussionmentioning

confidence: 99%

Functional and prognostic implications of cardiac magnetic resonance feature tracking-derived remote myocardial strain analyses in patients following acute myocardial infarction

et al. 2020

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Background Cardiac magnetic resonance myocardial feature tracking (CMR-FT)-derived global strain assessments provide incremental prognostic information in patients following acute myocardial infarction (AMI). Functional analyses of the remote myocardium (RM) are scarce and whether they provide an additional prognostic value in these patients is unknown. Methods 1034 patients following acute myocardial infarction were included. CMR imaging and strain analyses as well as infarct size quantification were performed after reperfusion by primary percutaneous coronary intervention. The occurrence of major adverse cardiac events (MACE) within 12 months after the index event was defined as primary clinical endpoint. Results Patients with MACE had significantly lower RM circumferential strain (CS) compared to those without MACE. A cutoff value for RM CS of − 25.8% best identified high-risk patients (p < 0.001 on log-rank testing) and impaired RM CS was a strong predictor of MACE (HR 1.05, 95% CI 1.07–1.14, p = 0.003). RM CS provided further risk stratification among patients considered at risk according to established CMR parameters for (1) patients with reduced left ventricular ejection fraction (LVEF) ≤ 35% (p = 0.038 on log-rank testing), (2) patients with reduced global circumferential strain (GCS) > − 18.3% (p = 0.015 on log-rank testing), and (3) patients with large microvascular obstruction ≥ 1.46% (p = 0.002 on log-rank testing). Conclusion CMR-FT-derived RM CS is a useful parameter to characterize the response of the remote myocardium and allows improved stratification following AMI beyond commonly used parameters, especially of high-risk patients. Trial registration ClinicalTrials.gov, NCT00712101 and NCT01612312 Graphic abstract Defining remote segments (R) in the presence of infarct areas (I) for the analysis of remote circumferential strain (CS). Remote CS was significantly lower in patients who suffered major adverse cardiac events (MACE) and a cutoff value for remote CS of − 25.8% best identified high-risk patients. In addition, impaired remote CS ≥ − 25.8 % (Remote −) and preserved remote CS < − 25.8 % (Remote +) enabled further risk stratification when added to established parameters like left ventricular ejection fraction (LVEF), global circumferential strain (GCS) or microvascular obstruction (MVO).

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Subacute ghrelin administration inhibits apoptosis and improves ultrastructural abnormalities in remote myocardium post-myocardial infarction

Cited by 14 publications

References 48 publications

Pretreatment of ghrelin protects H9c2 cells against hypoxia/reoxygenation-induced cell death via PI3K/AKT and AMPK pathways

Pretreatment of ghrelin protects H9c2 cells against hypoxia/reoxygenation-induced cell death via PI3K/AKT and AMPK pathways

A high‐fat diet rich in corn oil induces cardiac fibrosis in rats by activating JAK2/STAT3 and subsequent activation of ANG II/TGF‐1β/Smad3 pathway: The role of ROS and IL‐6 trans‐signaling

Functional and prognostic implications of cardiac magnetic resonance feature tracking-derived remote myocardial strain analyses in patients following acute myocardial infarction

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