HIF-1α-induced upregulated miR-322 forms a feedback loop by targeting Smurf2 and Smad7 to activate Smad3/β-catenin/HIF-1α, thereby improving myocardial ischemia-reperfusion injury

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doi: 10.1002/cbin.11954.


Online ahead of print.

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Wei Dong et al.


Cell Biol Int.


.

Abstract

Myocardial ischemia/reperfusion injury (MIRI) is a major cause of heart failure after myocardial infarction. It has been reported that miR-322 is involved in MIRI progression, while the molecular mechanism of miR-322 in regulating MIRI progression needs to be further probed. MIRI cell model was established by oxygen-glucose deprivation/reoxygenation (OGD/R). Cell viability was assessed using MTS assay. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining were employed to analyze cell apoptosis. In addition, the interactions between miR-322, Smad7/Smurf2, hypoxia-inducible factor alpha (HIF-1α), and β-catenin were verified by dual-luciferase reporter gene assay. Our results displayed that miR-322 was significantly downregulated in OGD/R-treated H9c2 cells, and its overexpression resulted in increased cell viability and reduced the apoptosis. Smurf2 and Smad7 were identified as the direct targets of miR-322. Smad7 knockdown or Smurf2 knockdown increased OGD/R-treated H9c2 cell viability and suppressed the apoptosis. Meanwhile, miR-322 mimics abolished the mitigating effect of Smad7 or Smurf2 overexpression on MIRI. In addition, the Smad3/β-catenin pathway was identified as the downstream pathway of Smurf2/Smad7. Moreover, it was found that HIF-1α interacted with the miR-322 promoter, and β-catenin interacted with the HIF-1α promoter to form a loop. HIF-1α-induced upregulated miR-322 activated the Smad3/β-catenin pathway by targeting Smurf2 and Smad7 to improve MIRI; meanwhile, β-catenin/HIF-1α formed a positive feedback loop to continuously improve MIRI.


Keywords:

HIF-1α; Smad7; Smurf2; miR-322; myocardial ischemia/reperfusion injury; positive feedback loop; the Smad3/β-catenin.

References

REFERENCES

    1. Bai, X., Niu, R., Liu, J., Pan, X., Wang, F., Yang, W., Wang, L., & Sun, L. (2021). Roles of noncoding RNAs in the initiation and progression of myocardial ischemia-reperfusion injury. Epigenomics, 13(9), 715-743.

    1. Ban, Q., Qiao, L., Xia, H., Xie, B., Liu, J., Ma, Y., Zhang, L., Zhang, M., Liu, L. G., Jiao, W., Yang, S., Li, Z., Zheng, S., Liu, D., Xia, J., & Qi, Z. (2020). β-catenin regulates myocardial ischemia/reperfusion injury following heterotopic heart transplantation in mice by modulating PTEN pathways. American Journal of Translational Research, 12(8), 4757-4771.

    1. Blank, M., Tang, Y., Yamashita, M., Burkett, S. S., Cheng, S. Y., & Zhang, Y. E. (2012). A tumor suppressor function of Smurf2 associated with controlling chromatin landscape and genome stability through RNF20. Nature Medicine, 18(2), 227-234.

    1. Cai, X., Wang, S., Hong, L., Yu, S., Li, B., Zeng, H., Yang, X., Zhang, P., & Shao, L. (2021). Inhibition of miR-322-5p protects cardiac myoblast cells against hypoxia-induced apoptosis and injury through regulating CIAPIN1. Journal of Cardiovascular Pharmacology, 77(2), 200-207.

    1. Chee, N. T., Lohse, I., & Brothers, S. P. (2019). mRNA-to-protein translation in hypoxia. Molecular Cancer, 18(1), 49.

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Plaque characterization of a saphenous vein graft by near-infrared spectroscopy and histopathology in a patient with a percutaneous coronary intervention

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Case Reports

. 2023 Mar 23.


doi: 10.1002/ccd.30641.


Online ahead of print.

Affiliations

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Case Reports

Hiroki Mori et al.


Catheter Cardiovasc Interv.


.

Abstract

Near-infrared spectroscopy (NIRS) is an intravascular imaging (IVUS) modality that detects lipid core plaques in the vessel wall, which are regarded as high-risk plaques for distal embolization in percutaneous coronary interventions (PCI). Saphenous vein graft (SVG) lesions have friable lipid-rich plaques and thrombus prone to distal embolization. The plaque characterization of SVG by NIRS was confirmed herein for the first time with histopathology before and after PCI. The present case was a man in his 60 s with a history of coronary artery bypass graft surgery. Coronary angiography revealed severe stenosis in multiple segments of the SVG to left circumflex artery (LCX). NIRS IVUS showed large amounts of lipidic materials at each segment before PCI. After balloon dilatation, NIRS IVUS revealed a marked reduction in yellow signals on chemography. A histopathological analysis of the captured specimen showed that it was mainly composed of fibrin and contained numerous histiocytes with foam cells, lymphocytes, and other cells, which was consistent with the histopathological findings of plaque rupture.

References

REFERENCES

    1. Waxman S, Dixon SR, L’Allier P, et al. In vivo validation of a catheter-based near-infrared spectroscopy system for detection of lipid core coronary plaques. JACC. 2009;2(7):858-868. doi:10.1016/j.jcmg.2009.05.001

    1. Raghunathan D, Abdel-Karim A-RR, Papayannis AC, et al. Relation between the presence and extent of coronary lipid core plaques detected by near-infrared spectroscopy with postpercutaneous coronary intervention myocardial infarction. Am J Cardiol. 2011;107(11):1613-1618. https://linkinghub.elsevier.com/retrieve/pii/S0002914911003882

    1. Goldstein JA, Maini B, Dixon SR, et al. Detection of lipid-core plaques by intracoronary near-infrared spectroscopy identifies high risk of periprocedural myocardial infarction. Circ Cardiovasc Interven. 2011;4(5):429-437.

    1. Madder RD, Puri R, Muller JE, et al. Confirmation of the intracoronary near-infrared spectroscopy threshold of lipid-rich plaques that underlie ST-segment-elevation myocardial infarction. Arterioscler Thromb Vasc Biol. 2016;36(5):1010-1015.

    1. Klima T, Beard EF, Milam JD, Reul GJ Jr, Cooley DA. Atherosclerosis of aortocoronary artery saphenous vein bypass grafts. Cardiovasc Dis. 1979;6(3):318-323.

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Association of Device Industry Payments, Physician Supply, and Regional Utilization of Orthopedic and Cardiac Procedures

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Background:

Geographic variation in high-cost medical procedure utilization in the USA is not fully explained by patient factors but may be influenced by the supply of procedural physicians and marketing payments.


Objective:

To examine the association between physician supply, medical device-related marketing payments to physicians, and utilization of knee arthroplasty (KA) and percutaneous coronary interventions (PCI) within hospital referral regions (HRRs).


Design:

Cross-sectional analysis of data from the 2018 CMS Open Payments database and procedural utilization data from the CMS Provider Utilization and Payment database.


Participants:

Medicare-participating procedural cardiologists and orthopedic surgeons.


Main measures:

Regional rates of PCIs and KAs per 100,000 Medicare fee-for-service (FFS) beneficiaries were estimated after adjustment for beneficiary demographics.


Key results:

Across 306 HRRs, there were 109,301 payments (value $17,554,728) to cardiologists for cardiac stents and 68,132 payments (value $40,492,126) to orthopedic surgeons for prosthetic knees. Among HRRs, one additional interventional cardiologist was associated with an increase of 12.9 (CI, 9.3-16.5) PCIs per 100,000 beneficiaries, and one additional orthopedic surgeon was associated with an increase of 20.6 (CI, 16.9-24.4) KAs per 100,000 beneficiaries. A $10,000 increase in gift payments from stent manufacturers was associated with an increase of 26.0 (CI, 5.1-46.9) PCIs per 100,000 beneficiaries, while total and service payments were not associated with greater regional PCI utilization. A $10,000 increase in total payments from knee prosthetic manufacturers was associated with an increase of 2.9 (CI, 1.4-4.5) KAs per 100,000 beneficiaries, while a similar increase in gift and service payments was associated with an increase of 14.5 (CI, 5.0-24.1) and 3.4 (CI, 1.6-5.2) KAs, respectively.


Conclusions:

Among Medicare FFS beneficiaries, regional supply of physicians and receipt of industry payments were associated with greater use of PCIs and KAs. Relationships between payments and procedural utilization were more consistent for KAs, a largely elective procedure, compared to PCIs, which may be elective or emergent.


Keywords:

cardiology; conflict of interest; joint arthroplasty; marketing payments; medical devices; orthopedics; percutaneous coronary intervention; procedure utilization.

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Effect of Intravenous Iron-Carbohydrate Complexes in Patients With Heart Failure With Reduced Ejection Fraction and Iron Deficiency: A Meta-analysis of Randomized Controlled Trials

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. 2023 Mar 21;S1109-9666(23)00036-2.


doi: 10.1016/j.hjc.2023.03.005.


Online ahead of print.

Affiliations

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Rena Mototani et al.


Hellenic J Cardiol.


.

No abstract available


Keywords:

Heart failure; Iron deficiency; Iron-carbohydrate complex; Meta-analysis.

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Left-ventricular Unloading in Extracorporeal Cardiopulmonary Resuscitation due to Acute Myocardial Infarction – A Multicenter Study

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doi: 10.1016/j.resuscitation.2023.109775.


Online ahead of print.

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Tharusan Thevathasan et al.


Resuscitation.


.

Abstract

Background Guidelines advocate the use of extracorporeal cardio-pulmonary resuscitation with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in selected patients with cardiac arrest. Effects of concomitant left-ventricular (LV) unloading with Impella® (ECMELLA) remain unclear. This is the first study to investigate whether treatment with ECMELLA was associated with improved outcomes in patients with refractory cardiac arrest caused by acute myocardial infarction (AMI). Methods This study was approved by the local ethical committee. Patients treated with ECMELLA at three centers between 2016 and 2021 were propensity score (PS)-matched to patients receiving VA-ECMO based on age, electrocardiogram rhythm, cardiac arrest location and Survival After Veno-Arterial ECMO (SAVE) score. Cox proportional-hazard and Poisson regression models were used to analyse 30-day mortality rate (primary outcome), hospital and intensive care unit (ICU) length of stay (LOS) (secondary outcomes). Sensitivity analyses on patient demographics and cardiac arrest parameters were performed. Results 95 adult patients were included in this study, out of whom 34 pairs of patients were PS-matched. ECMELLA treatment was associated with decreased 30-day mortality risk (Hazard Ratio [HR] 0.53 [95% Confidence Interval (CI) 0.31-0.91], P=0.021), prolonged hospital (Incidence Rate Ratio (IRR) 1.71 [95% CI 1.50-1.95], P<0.001) and ICU LOS (IRR 1.81 [95% CI 1.57-2.08], P<0.001). LV ejection fraction significantly improved until ICU discharge in the ECMELLA group. Especially patients with prolonged low-flow time and high initial lactate benefited from additional LV unloading. Conclusions LV unloading with Impella® concomitant to VA-ECMO therapy in patients with therapy-refractory cardiac arrest due to AMI was associated with improved patient outcomes.


Keywords:

Cardiac Arrest; Impella; acute myocardial infarction; extracorporeal cardio-pulmonary resuscitation; veno-arterial extracorporeal membrane oxygenation.

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Infection as an under-recognized precipitant of acute heart failure: prognostic and therapeutic implications

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Review


doi: 10.1007/s10741-023-10303-8.


Online ahead of print.

Affiliations

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Review

Sofia Bezati et al.


Heart Fail Rev.


.

Abstract

As the prevalence of heart failure (HF) continues to rise, prompt diagnosis and management of various medical conditions, which may lead to HF exacerbation and result in poor patient outcomes, are of paramount importance. Infection has been identified as a common, though under-recognized, precipitating factor of acute heart failure (AHF), which can cause rapid development or deterioration of HF signs and symptoms. Available evidence indicates that infection-related hospitalizations of patients with AHF are associated with higher mortality, protracted length of stay, and increased readmission rates. Understanding the intricate interaction of both clinical entities may provide further therapeutic strategies to prevent the occurrence of cardiac complications and improve prognosis of patients with AHF triggered by infection. The purpose of this review is to investigate the incidence of infection as a causative factor in AHF, explore its prognostic implications, elucidate the underlying pathophysiological mechanisms, and highlight the basic principles of the initial diagnostic and therapeutic interventions in the emergency department.


Keywords:

Acute heart failure; Infection; Management; Pathophysiology.

References

    1. Farmakis D, Parissis J, Karavidas A et al (2015) In-hospital management of acute heart failure: practical recommendations and future perspectives. Int J Cardiol 201:231–236. https://doi.org/10.1016/j.ijcard.2015.08.030



      DOI



      PubMed

    1. Farmakis D, Parissis J, Lekakis J, Filippatos G (2015) Acute heart failure: epidemiology, risk factors, and prevention. Rev Esp Cardiol (Engl Ed) 68(3):245–248. https://doi.org/10.1016/j.rec.2014.11.004



      DOI



      PubMed

    1. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M et al (2021) 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 42(36):3599–3726



      DOI



      PubMed

    1. Arrigo M, Jessup M, Mullens W, Reza N, Shah AM, Sliwa K et al (2020) (2020) Acute heart failure. Nat Rev Dis Primers 6(1):16. https://doi.org/10.1038/s41572-020-0151-7



      DOI



      PubMed



      PMC

    1. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS et al (2016) 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 37(27):2129–2200. https://doi.org/10.1093/eurheartj/ehw128



      DOI



      PubMed

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Evaluation of hypercholesterolemia management in at-risk patients by cardiologists in France: a case vignette-based study

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doi: 10.57264/cer-2022-0181.


Online ahead of print.

Affiliations

Item in Clipboard

Jean Ferrières et al.


J Comp Eff Res.


.

Abstract

Aim: This online interactive survey investigated lipid-lowering approaches of French cardiologists in high- and very high-cardiovascular risk patients with hypercholesterolemia. Materials & methods: Physicians assessed three hypothetical patients at three clinic visits, and selected the patients’ cardiovascular risk category, target low-density lipoprotein cholesterol (LDL-C) and treatment. Results: A total of 162 physicians completed 480 risk assessments; 58% of assessments correctly categorized the hypothetical patients. Most physicians chose the correct LDL-C target for one of the very high-risk patients, but higher-than-recommended targets were selected for the other very high-risk patient and the high-risk patient. Statins were the most commonly chosen treatment. Conclusion: French cardiologists often underestimate cardiovascular risk in patients with hypercholesterolemia, select a higher-than-recommended LDL-C target and prescribe less intensive treatment than that recommended by guidelines.


Keywords:

France; cardiologists; cardiovascular risk; case-vignette; ezetimibe; hypercholesterolemia; lipid-lowering; online interactive survey; statin; treatment.

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Creation of online maps for voluntary out-of-home firearm storage: Experiences and opportunities

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doi: 10.1016/j.pmedr.2023.102167.


eCollection 2023 Apr.

Affiliations

Item in Clipboard

Marian E Betz et al.


Prev Med Rep.


.

Abstract

Online maps showing locations for voluntary, temporary firearm storage are a novel approach in suicide and injury prevention. A study team from two states with maps (Colorado and Washington) interviewed leaders from six additional states with maps and six without. Key considerations for map creation were: trust and partnerships; legal issues; funding; and map maintenance. Addressing these considerations – through stronger networks, liability protection, or sustainable programming – may enhance dissemination and use of out-of-home firearm storage options.


Keywords:

Community program; Firearm; Injury prevention; Qualitative; Storage; Suicide.

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Narrative review of single ventricle: where are we after 40 years?

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Background and objective:

Key medical and surgical advances have been made in the longitudinal management of patients with “functionally” single ventricle physiology, with the principles of Fontan circulation applied to other complex congenital heart defects. The purpose of this article is to review all of the innovations, starting from fetal life, that led to a change of strategy for single ventricle.


Methods:

Our literature review included all full articles published in English language on the Cochrane, MedLine, and Embase with references to “single ventricle” and “univentricular hearts”, including the initial history of the treatments for this congenital heart defects as well as the innovations reported within the last decades.


Key content and findings:

All innovations introduced have been analyzed, including: (I) fetal diagnosis and interventions, in particular to prevent or reduce brain damages; (II) neonatal care; (III) post-natal diagnosis; (IV) interventional cardiology procedures; (V) surgical procedures, including neonatal palliations, hybrid procedures, bidirectional Glenn and variations, Fontan completion, biventricular repair; (VI) peri-operative management; (VII) Fontan failure, with Fontan take-down and conversion, and mechanical circulatory support; (VIII) transplantation, including heart, heart and lung, heart and liver; (IX) exercise; (X) pregnancy; (XI) adolescents and adults without Fontan completion; (XII) future studies, including experimental studies on animals, computational studies, genetics, stem cells and bioengineering.


Conclusions:

These last 40 years have certainly changed the course of natural history for children born with any form of “functionally” single ventricle, thanks to the improvement in diagnostic and treatment techniques, and particularly to the increased knowledge of the morphology and function of these complex hearts, from fetal to adult life. There is still much left unexplored and room for improvement, and all efforts should be concentrated in collaborations among different institutions and specialties, focused on the same matter.


Keywords:

Congenital heart defects; Fontan procedure; congenital heart surgery; single ventricle; univentricular heart.

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Evaluation of right ventricular strain in two separate cohorts with precapillary pulmonary hypertension

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. 2023 Mar 5;13(1):e12204.


doi: 10.1002/pul2.12204.


eCollection 2023 Jan.

Affiliations

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Lauren M Crossman et al.


Pulm Circ.


.

Abstract

Evaluation for right ventricular (RV) dysfunction is an important part of risk assessment in care of patients with pulmonary hypertension (PH) as it is associated with morbidity and mortality. Echocardiography provides a widely available and acceptable method to assess RV function. RV global longitudinal strain (RVGLS), a measure of longitudinal shortening of RV deep muscle fibers obtained by two-dimensional echocardiography, was previously shown to predict short-term mortality in patients with PH. The purpose of the current study was to assess the performance of RVGLS in predicting 1-year outcomes in PH. We retrospectively identified 83 subjects with precapillary PH and then enrolled 50 consecutive prevalent pulmonary arterial hypertension (PAH) subjects into a prospective validation cohort. Death as well as combined morbidity and mortality events at 1 year were assessed as outcomes. In the retrospective cohort, 84% of patients had PAH and the overall 1-year mortality rate was 16%. Less negative RVGLS was marginally better than tricuspid annular plane systolic excursion (TAPSE) as a predictor for death. However, in the prospective cohort, 1-year mortality was only 2%, and RVGLS was not predictive of death or a combined morbidity and mortality outcome. This study supports that RV strain and TAPSE have similar 1-year outcome predictions but highlights that low TAPSE or less negative RV strain measures are often false-positive in a cohort with low baseline mortality risk. While RV failure is considered the final common pathway for disease progression in PAH, echocardiographic measures of RV function may be less informative of risk in serial follow-up of treated PAH patients.


Keywords:

clinical studies; echocardiography; mortality/survival; prognosis; pulmonary hypertension.

Conflict of interest statement

The authors declare no conflict of interest.

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