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Special Issue "Positive and Negative Determinants of Ischaemic Injury—Co-Morbidities and Cardioprotection"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 May 2019).

Special Issue Editors

Prof. Dr. Jason Peart
Website
Guest Editor
School of Medical Science, Griffith University, Southport, QLD 4217, Australia
Interests: ischaemia-reperfusion; cardioprotection; cardioprotective signaling; age; diabetes; hypertrophy
Special Issues and Collections in MDPI journals
Prof. Dr. John Headrick
Website
Guest Editor
School of Medical Science, Griffith University, Southport, QLD 4217, Australia
Interests: ischaemia-reperfusion; cardioprotection; cardioprotective signaling; age; diabetes; hypertrophy

Special Issue Information

Dear Colleagues,

Ischaemic heart disease and associated heart attack (acute myocardial infarction, AMI), together with subsequent heart failure are the lead causes of death worldwide, presenting a profound healthcare burden. There is thus a great need for adjunctive protective therapy that can be applied prior to, with or after reperfusion to improve both short and longer term outcomes from AMI (or surgical ischaemia), and extend the effective window for reperfusion. Thus far, no adjunctive treatment has been developed that is effective in the context of the co-morbidities associated with ischaemic heart disease. Processes of, and outcomes from cardiac ischaemia-reperfusion injury are influenced by multiple factors, including comorbidities (such as diabetes, obesity, hypertension etc), sex, age and other gene and phenotypic features. The long-running and unmet challenge of cardioprotection can only be met through consideration of these critical positive and negative determinants of outcome.

This Special Issue, “Positive and Negative Determinants of Ischaemic Injury – Co-Morbidities and Cardioprotection” will focus on novel, emerging paradigms from the study (original research articles or reviews) around the current understanding of the effects of comorbid conditions on myocardial ischaemia-reperfusion processes, the influences on cardioprotective signalling and outcomes, and novel strategies for protecting the heart from accidental and surgical I-R.

Prof. Dr. Jason Peart
Prof. Dr. John Headrick
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Ischaemia-reperfusion
  • Precondtioning
  • Postconditioning
  • Cardioprotection
  • Cell signaling
  • Age
  • Diabetes
  • Obesity
  • Hypercholesterolaemia
  • Hypertrophy
  • Chronic Diseases
  • Receptor Signaling

Published Papers (6 papers)

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Open AccessArticle
Helium-Induced Changes in Circulating Caveolin in Mice Suggest a Novel Mechanism of Cardiac Protection
Int. J. Mol. Sci. 2019, 20(11), 2640; https://doi.org/10.3390/ijms20112640 - 29 May 2019
Cited by 1
Abstract
The noble gas helium (He) induces cardioprotection in vivo through unknown molecular mechanisms. He can interact with and modify cellular membranes. Caveolae are cholesterol and sphingolipid-enriched invaginations of the plasma-membrane-containing caveolin (Cav) proteins that are critical in protection of the heart. Mice (C57BL/6J) [...] Read more.
The noble gas helium (He) induces cardioprotection in vivo through unknown molecular mechanisms. He can interact with and modify cellular membranes. Caveolae are cholesterol and sphingolipid-enriched invaginations of the plasma-membrane-containing caveolin (Cav) proteins that are critical in protection of the heart. Mice (C57BL/6J) inhaled either He gas or adjusted room air. Functional measurements were performed in the isolated Langendorff perfused heart at 24 h post He inhalation. Electron paramagnetic resonance spectrometry (EPR) of samples was carried out at 24 h post He inhalation. Immunoblotting was used to detect Cav-1/3 expression in whole-heart tissue, exosomes isolated from platelet free plasma (PFP) and membrane fractions. Additionally, transmission electron microscopy analysis of cardiac tissue and serum function and metabolomic analysis were performed. In contrast to cardioprotection observed in in vivo models, the isolated Langendorff perfused heart revealed no protection after He inhalation. However, levels of Cav-1/3 were reduced 24 h after He inhalation in whole-heart tissue, and Cav-3 was increased in exosomes from PFP. Addition of serum to muscle cells in culture or naïve ventricular tissue increased mitochondrial metabolism without increasing reactive oxygen species generation. Primary and lipid metabolites determined potential changes in ceramide by He exposure. In addition to direct effects on myocardium, He likely induces the release of secreted membrane factors enriched in caveolae. Our results suggest a critical role for such circulating factors in He-induced organ protection. Full article
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Open AccessArticle
Cognitive Deficits Following a Post-Myocardial Infarct in the Rat Are Blocked by the Serotonin-Norepinephrine Reuptake Inhibitor Desvenlafaxine
Int. J. Mol. Sci. 2018, 19(12), 3748; https://doi.org/10.3390/ijms19123748 - 26 Nov 2018
Cited by 1
Abstract
Myocardial infarction (MI) in animal models induces cognitive deficits as well as the activation of caspase in the limbic system; both can be blocked by 2 weeks of treatment following MI using tricyclic antidepressants or selective serotonin uptake blockers. Here we used three [...] Read more.
Myocardial infarction (MI) in animal models induces cognitive deficits as well as the activation of caspase in the limbic system; both can be blocked by 2 weeks of treatment following MI using tricyclic antidepressants or selective serotonin uptake blockers. Here we used three different treatment schedules to test the short- and long-term effects of the combined serotonin-norepinephrine reuptake inhibitor desvenlafaxine on post-MI-associated cognitive deficits and caspase activation. MI was induced in 39 young adult rats, and 39 rats served as sham-operated controls. Desvenlafaxine (3 mg/kg/day, i.p.) or saline was administered according to one of three schedules: (1) for 2 weeks, starting right after surgery; (2) for 16 weeks, starting 2 weeks after surgery; (3) for 16 weeks, starting right after surgery. Behavior was tested 2 weeks (social interaction, passive avoidance) and 16 weeks (forced swimming, Morris water maze) after surgery. Caspase-3 and caspase-6 activities were measured 16 weeks after surgery. At 2 and 16 weeks post-surgery, saline-treated MI rats displayed performance deficits compared to desvenlafaxine-treated rats, regardless of the treatment schedule. Caspase-3 activity was higher in the amygdala (medial and lateral) and hippocampal CA3 region in untreated MI rats, whereas caspase-6 activity was higher in the CA1 region. Caspase-6 activity correlated positively with deficits in the Morris water maze. These results indicate that, independently of treatment schedules, various treatment schedules with desvenlafaxine can prevent MI-associated cognitive deficits and decrease caspase activities in the limbic system. Full article
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Open AccessReview
Recent Advances in Pharmacological and Non-Pharmacological Strategies of Cardioprotection
Int. J. Mol. Sci. 2019, 20(16), 4002; https://doi.org/10.3390/ijms20164002 - 16 Aug 2019
Cited by 9
Abstract
Ischemic heart diseases (IHD) are the leading cause of death worldwide. Although the principal form of treatment of IHD is myocardial reperfusion, the recovery of coronary blood flow after ischemia can cause severe and fatal cardiac dysfunctions, mainly due to the abrupt entry [...] Read more.
Ischemic heart diseases (IHD) are the leading cause of death worldwide. Although the principal form of treatment of IHD is myocardial reperfusion, the recovery of coronary blood flow after ischemia can cause severe and fatal cardiac dysfunctions, mainly due to the abrupt entry of oxygen and ionic deregulation in cardiac cells. The ability of these cells to protect themselves against injury including ischemia and reperfusion (I/R), has been termed “cardioprotection”. This protective response can be stimulated by pharmacological agents (adenosine, catecholamines and others) and non-pharmacological procedures (conditioning, hypoxia and others). Several intracellular signaling pathways mediated by chemical messengers (enzymes, protein kinases, transcription factors and others) and cytoplasmic organelles (mitochondria, sarcoplasmic reticulum, nucleus and sarcolemma) are involved in cardioprotective responses. Therefore, advancement in understanding the cellular and molecular mechanisms involved in the cardioprotective response can lead to the development of new pharmacological and non-pharmacological strategies for cardioprotection, thus contributing to increasing the efficacy of IHD treatment. In this work, we analyze the recent advances in pharmacological and non-pharmacological strategies of cardioprotection. Full article
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Open AccessReview
Hurdles to Cardioprotection in the Critically Ill
Int. J. Mol. Sci. 2019, 20(15), 3823; https://doi.org/10.3390/ijms20153823 - 05 Aug 2019
Abstract
Cardiovascular disease is the largest contributor to worldwide mortality, and the deleterious impact of heart failure (HF) is projected to grow exponentially in the future. As heart transplantation (HTx) is the only effective treatment for end-stage HF, development of mechanical circulatory support (MCS) [...] Read more.
Cardiovascular disease is the largest contributor to worldwide mortality, and the deleterious impact of heart failure (HF) is projected to grow exponentially in the future. As heart transplantation (HTx) is the only effective treatment for end-stage HF, development of mechanical circulatory support (MCS) technology has unveiled additional therapeutic options for refractory cardiac disease. Unfortunately, despite both MCS and HTx being quintessential treatments for significant cardiac impairment, associated morbidity and mortality remain high. MCS technology continues to evolve, but is associated with numerous disturbances to cardiac function (e.g., oxidative damage, arrhythmias). Following MCS intervention, HTx is frequently the destination option for survival of critically ill cardiac patients. While effective, donor hearts are scarce, thus limiting HTx to few qualifying patients, and HTx remains correlated with substantial post-HTx complications. While MCS and HTx are vital to survival of critically ill cardiac patients, cardioprotective strategies to improve outcomes from these treatments are highly desirable. Accordingly, this review summarizes the current status of MCS and HTx in the clinic, and the associated cardiac complications inherent to these treatments. Furthermore, we detail current research being undertaken to improve cardiac outcomes following MCS/HTx, and important considerations for reducing the significant morbidity and mortality associated with these necessary treatment strategies. Full article
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Open AccessReview
Influence of Cardiovascular Risk Factors, Comorbidities, Medication Use and Procedural Variables on Remote Ischemic Conditioning Efficacy in Patients with ST-Segment Elevation Myocardial Infarction
Int. J. Mol. Sci. 2019, 20(13), 3246; https://doi.org/10.3390/ijms20133246 - 02 Jul 2019
Cited by 2
Abstract
Remote ischemic conditioning (RIC) confers cardioprotection in patients with ST-segment elevation myocardial infarction (STEMI). Despite intense research, the translation of RIC into clinical practice remains a challenge. This may, at least partly, be due to confounding factors that may modify the efficacy of [...] Read more.
Remote ischemic conditioning (RIC) confers cardioprotection in patients with ST-segment elevation myocardial infarction (STEMI). Despite intense research, the translation of RIC into clinical practice remains a challenge. This may, at least partly, be due to confounding factors that may modify the efficacy of RIC. The present review focuses on cardiovascular risk factors, comorbidities, medication use and procedural variables which may modify the efficacy of RIC in patients with STEMI. Findings of such efficacy modifiers are based on subgroup and post-hoc analyses and thus hold risk of type I and II errors. Although findings from studies evaluating influencing factors are often ambiguous, some but not all studies suggest that smoking, non-statin use, infarct location, area-at-risk of infarction, pre-procedural Thrombolysis in Myocardial Infarction (TIMI) flow, ischemia duration and coronary collateral blood flow to the infarct-related artery may influence on the cardioprotective efficacy of RIC. Results from the on-going CONDI2/ERIC-PPCI trial will determine any clinical implications of RIC in the treatment of patients with STEMI and predefined subgroup analyses will give further insight into influencing factors on the efficacy of RIC. Full article
Open AccessArticle
Genetic Deletion or Pharmacological Inhibition of Soluble Epoxide Hydrolase Ameliorates Cardiac Ischemia/Reperfusion Injury by Attenuating NLRP3 Inflammasome Activation
Int. J. Mol. Sci. 2019, 20(14), 3502; https://doi.org/10.3390/ijms20143502 - 17 Jul 2019
Cited by 7
Abstract
Activation of the nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome cascade has a role in the pathogenesis of ischemia/reperfusion (IR) injury. There is growing evidence indicating cytochrome p450 (CYP450)-derived metabolites of n-3 and n-6 polyunsaturated fatty acids (PUFAs) [...] Read more.
Activation of the nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome cascade has a role in the pathogenesis of ischemia/reperfusion (IR) injury. There is growing evidence indicating cytochrome p450 (CYP450)-derived metabolites of n-3 and n-6 polyunsaturated fatty acids (PUFAs) possess both adverse and protective effects in the heart. CYP-derived epoxy metabolites are rapidly hydrolyzed by the soluble epoxide hydrolase (sEH). The current study hypothesized that the cardioprotective effects of inhibiting sEH involves limiting activation of the NLRP3 inflammasome. Isolated hearts from young wild-type (WT) and sEH null mice were perfused in the Langendorff mode with either vehicle or the specific sEH inhibitor t-AUCB. Improved post-ischemic functional recovery and better mitochondrial respiration were observed in both sEH null hearts or WT hearts perfused with t-AUCB. Inhibition of sEH markedly attenuated the activation of the NLRP3 inflammasome complex and limited the mitochondrial localization of the fission protein dynamin-related protein-1 (Drp-1) triggered by IR injury. Cardioprotective effects stemming from the inhibition of sEH included preserved activities of both cytosolic thioredoxin (Trx)-1 and mitochondrial Trx-2 antioxidant enzymes. Together, these data demonstrate that inhibiting sEH imparts cardioprotection against IR injury via maintaining post-ischemic mitochondrial function and attenuating a detrimental innate inflammatory response. Full article
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