Myocardial ischaemia reperfusion injury and cardioprotection in the presence of sensory neuropathy: Therapeutic options

Bencsik, Péter; Gömöri, Kamilla; Szabados, Tamara; Stella, Péter; Helyes, Zsuzsanna; Jancsó, Gábor; Ferdinándy, Péter; Görbe, Anikó

doi:10.1111/bph.15021

Cited by 15 publications

(9 citation statements)

References 154 publications

(219 reference statements)

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“…USPs act on specific proteins, and therefore controlling them can improve prognosis (da Silva et al, 2009;Sacco et al, 2010;Schwickart et al, 2010;Tavana and Gu, 2017). For example, the proteasome inhibitor bortezomib improves myocardial ischemia/ reperfusion injury, prevents post-ischemic ventricular tachyarrhythmia, promotes cardiac hypertrophy regression, and reverses vascular endothelial dysfunction caused by diabetes (Raimondi et al, 2019;Bencsik et al, 2020). In addition, inhibition of USP1 has the potential to target a variety of cancers (Sacco et al, 2010;Chen et al, 2011;Ma et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Primaquine Diphosphate, a Known Antimalarial Drug, Blocks Vascular Leakage Acting Through Junction Stabilization

Noh

Zhang²,

Kim

et al. 2021

Front. Pharmacol.

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Endothelial barrier integrity is important for vascular homeostasis, and hyperpermeability participates in the progression of many pathological states, such as diabetic retinopathy, ischemic stroke, chronic bowel disease, and inflammatory disease. Here, using drug repositioning, we discovered that primaquine diphosphate (PD), previously known as an antimalarial drug, was a potential blocker of vascular leakage. PD inhibited the linear pattern of vascular endothelial growth factors (VEGF)-induced disruption at the cell boundaries, blocked the formation of VEGF-induced actin stress fibers, and stabilized the cortactin actin rings in endothelial cells. PD significantly reduced leakage in the Miles assay and mouse model of streptozotocin (STZ)-induced diabetic retinopathy. Targeted prediction programs and deubiquitinating enzyme activity assays identified a potential mechanism of action for PD and demonstrated that this operates via ubiquitin specific protease 1 (USP1). USP1 inhibition demonstrated a conserved barrier function by inhibiting VEGF-induced leakage in endothelial permeability assays. Taken together, these findings suggest that PD could be used as a novel drug for vascular leakage by maintaining endothelial integrity.

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Section: Discussionmentioning

confidence: 99%

Primaquine Diphosphate, a Known Antimalarial Drug, Blocks Vascular Leakage Acting Through Junction Stabilization

Noh

Zhang²,

Kim

et al. 2021

Front. Pharmacol.

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“…Other papers in this Themed Issue give overviews of less studied confounding factors of cardioprotection. Bencsik et al (2020) review the effect of sensory neuropathy of diverse aetiology (including diabetes and hyperglycaemia) on cardioprotection and the mechanisms by which neuropathies may interfere with ischaemic heart disease and cardioprotective signalling. They also suggest future therapeutic options targeting both ischaemic heart and sensory neuropathy.…”

Section: Figurementioning

confidence: 99%

Risk factors, co‐morbidities, and co‐medications in cardioprotection: Importance for translation

Schulz

Andreadou

Hausenloy

et al. 2020

British J Pharmacology

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On behalf of the EU-CARDIOPROTECTION COST Action (CA16225 www.cardioprotection.eu), in this Themed Issue "Risk factors, comorbidities, and co-medications in cardioprotection," we provide an up-to-date account on the influence of cardiovascular risk factors on cardioprotection. In particular, the Themed Issue focusses on comorbidities and their co-medications on acute myocardial ischemia/ reperfusion injury, cardioprotection, and their importance in the development of new cardioprotective therapies from preclinical to clinical studies. Since the original observations in the mid-nineties showing that hypercholesterolaemia attenuated the effect of preconditioning in rabbits (Szilvassy et al., 1995) and rats (Ferdinandy et al., 1997), it has become evident that the cardioprotective signalling is markedly affected by risk factors such as aging, sex and environmental factors, as well as by co-morbidities and their medications (Ferdinandy,

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“…Ischemic heart disease belongs to the leading causes of death worldwide (Hausenloy et al, 2017). There is no effective cardioprotective drug therapy on the market to reduce tissue injury; however, the heart has adaptive mechanisms, e.g., ischemic preconditioning, ischemic postconditioning, and remote ischemic conditioning, which can decrease the tissue damage caused by a subsequent ischemic insult (Ferdinandy et al, 2014;Bencsik et al, 2020). These conditioning mechanisms are short, repeated ischemia/reperfusion cycles applied either on the myocardium or on a remote organ before, during, or after an ischemic insult (Ferdinandy et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…Sensory nerves innervating the heart are involved in cardiac adaptation mechanisms to ischemic injury (Bencsik et al, 2020;Szabados et al, 2020). The activation of the Transient Receptor Potential Vanilloid 1-(TRPV1-) expressing capsaicin-sensitive chemosensitive peptidergic afferents leads to the release of sensory neuropeptides (Holzer, 1988).…”

Section: Introductionmentioning

confidence: 99%

Somatostatin and Its Receptors in Myocardial Ischemia/Reperfusion Injury and Cardioprotection

et al. 2021

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Little is known about the role of the neuropeptide somatostatin (SST) in myocardial ischemia/reperfusion injury and cardioprotection. Here, we investigated the direct cardiocytoprotective effect of SST on ischemia/reperfusion injury in cardiomyocyte cultures, as well as the expression of SST and its receptors in pig and human heart tissues. SST induced a bell-shaped, concentration-dependent cardiocytoprotection in both adult rat primary cardiomyocytes and H9C2 cells subjected to simulated ischemia/reperfusion injury. Furthermore, in a translational porcine closed-chest acute myocardial infarction model, ischemic preconditioning increased plasma SST-like immunoreactivity. Interestingly, SST expression was detectable at the protein, but not at the mRNA level in the pig left ventricles. SSTR1 and SSTR2, but not the other SST receptors, were detectable at the mRNA level by PCR and sequencing in the pig left ventricle. Moreover, remote ischemic conditioning upregulated SSTR1 mRNA. Similarly, SST expression was also detectable in healthy human interventricular septum samples at the protein level. Furthermore, SST-like immunoreactivity decreased in interventricular septum samples of patients with ischemic cardiomyopathy. SSTR1, SSTR2, and SSTR5 but not SST and the other SST receptors were detectable at the mRNA level by sequencing in healthy human left ventricles. In addition, in healthy human left ventricle samples, SSTR1 and SSTR2 mRNAs were expressed especially in vascular endothelial and some other cell types as detected by RNA Scope®in situ hybridization. This is the first demonstration that SST exerts a direct cardiocytoprotective effect against simulated ischemia/reperfusion injury. Moreover, SST is expressed in the heart tissue at the peptide level; however, it is likely to be of sensory neural origin since its mRNA is not detectable. SSTR1 and SSTR2 might be involved in the cardioprotective action of SST, but other mechanisms cannot be excluded.

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Myocardial ischaemia reperfusion injury and cardioprotection in the presence of sensory neuropathy: Therapeutic options

Cited by 15 publications

References 154 publications

Primaquine Diphosphate, a Known Antimalarial Drug, Blocks Vascular Leakage Acting Through Junction Stabilization

Primaquine Diphosphate, a Known Antimalarial Drug, Blocks Vascular Leakage Acting Through Junction Stabilization

Risk factors, co‐morbidities, and co‐medications in cardioprotection: Importance for translation

Somatostatin and Its Receptors in Myocardial Ischemia/Reperfusion Injury and Cardioprotection

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