Combined hypoxia and sodium nitrite pretreatment for cardiomyocyte protection <i>in vitro</i>

Hsieh, Anne; Feric, Nicole; Radišić, Milica

doi:10.1002/btpr.2039

Cited by 12 publications

(10 citation statements)

References 77 publications

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“…Hsieh et al found that the simulation of IRI in hESC-CMs caused an increase in the qPCR ratio of anti-apopototic BCL-2 to the apoptotic BAX gene following a pretreatment with sodium nitrite [62]. Paloczi et al demonstrated the cardioprotective effect of exogenous nitric oxide supplementation in simulated IRI experiments on hESC-CMs derived from embryoid bodies (EB) [45].…”

Section: In Vitro Models Of Irimentioning

confidence: 99%

In Vitro Models of Ischemia-Reperfusion Injury

Chen

Vunjak-Novakovic

2018

Regen. Eng. Transl. Med.

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Timely reperfusion after a myocardial infarction is necessary to salvage the ischemic region; however, reperfusion itself is also a major contributor to the final tissue damage. Currently, there is no clinically relevant therapy available to reduce ischemia-reperfusion injury (IRI). While many drugs have shown promise in reducing IRI in preclinical studies, none of these drugs have demonstrated benefit in large clinical trials. Part of this failure to translate therapies can be attributed to the reliance on small animal models for preclinical studies. While animal models encapsulate the complexity of the systemic in vivo environment, they do not fully recapitulate human cardiac physiology. Furthermore, it is difficult to uncouple the various interacting pathways in vivo. In contrast, in vitro models using isolated cardiomyocytes allow studies of the direct effect of therapeutics on cardiomyocytes. External factors can be controlled in simulated ischemia-reperfusion to allow for better understanding of the mechanisms that drive IRI. In addition, the availability of cardiomyocytes derived from human induced pluripotent stem cells (hIPS-CMs) offers the opportunity to recapitulate human physiology in vitro. Unfortunately, hIPS-CMs are relatively fetal in phenotype, and are more resistant to hypoxia than the mature cells. Tissue engineering platforms can promote cardiomyocyte maturation for a more predictive physiologic response. These platforms can further be improved upon to account for the heterogenous patient populations seen in the clinical settings and facilitate the translation of therapies. Thereby, the current preclinical studies can be further developed using currently available tools to achieve better predictive drug testing and understanding of IRI. In this article, we discuss the state of the art of in vitro modeling of IRI, propose the roles for tissue engineering in studying IRI and testing the new therapeutic modalities, and how the human tissue models can facilitate translation into the clinic.

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Section: In Vitro Models Of Irimentioning

confidence: 99%

In Vitro Models of Ischemia-Reperfusion Injury

Chen

Vunjak-Novakovic

2018

Regen. Eng. Transl. Med.

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“…Indeed, several studies describe little or no response to I/R-mimetic conditions in unprimed hPSC-CMs, although showing minimal but relatively significant cardioprotection by the individual molecules of interest (Hsieh et al, 2015;Wei et al, 2017;Mo et al, 2019). Our own experiments with oxygen/glucose deprivation in microfluidic devices show clearly divergent responses of postnatal murine cardiomyocytes and unprimed hPSC-CMs characterized by abnormal intracellular glycogen stores (Martewicz et al, 2018).…”

Section: Ischemia/reperfusion Injury Modelingmentioning

confidence: 71%

Beyond Family: Modeling Non-hereditary Heart Diseases With Human Pluripotent Stem Cell-Derived Cardiomyocytes

2020

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Non-genetic cardiac pathologies develop as an aftermath of extracellular stressconditions. Nevertheless, the response to pathological stimuli depends deeply on intracellular factors such as physiological state and complex genetic backgrounds. Without a thorough characterization of their in vitro phenotype, modeling of maladaptive hypertrophy, ischemia and reperfusion injury or diabetes in human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) has been more challenging than hereditary diseases with defined molecular causes. In past years, greater insights into hPSC-CM in vitro physiology and advancements in technological solutions and culture protocols have generated cell types displaying stress-responsive phenotypes reminiscent of in vivo pathological events, unlocking their application as a reductionist model of human cardiomyocytes, if not the adult human myocardium. Here, we provide an overview of the available literature of pathology models for cardiac non-genetic conditions employing healthy (or asymptomatic) hPSC-CMs. In terms of numbers of published articles, these models are significantly lagging behind monogenic diseases, which misrepresents the incidence of heart disease causes in the human population.

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“…Similar results were presented by our group on mouse embryonic stem cell-derived cardiomyocytes, where NO had concentration-dependent direct cytoprotective action and soluble guanylate cyclase, PKG, and KATP channels play a role in the downstream pathway of SNAP-induced cytoprotection [ 15 ]. Hsieh et al showed recently that short pretreatment with NO donor (NaNO 2 ) combined with hypoxia protects neonatal cardiac myocyte but not cardiac fibroblast from hypoxic injury, and apoptosis decreased in human ES-derived cardiac myocytes [ 34 ]. These results further suggest that NO donors may protect stem cells implanted into ischemic areas of the myocardium.…”

Section: Discussionmentioning

confidence: 99%

Exogenous Nitric Oxide Protects Human Embryonic Stem Cell‐Derived Cardiomyocytes against Ischemia/Reperfusion Injury

Pálóczi

Varga

Apáti

et al. 2016

Oxidative Medicine and Cellular Longevity

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Background and Aims. Human embryonic stem cell- (hESC-) derived cardiomyocytes are one of the useful screening platforms of potential cardiocytoprotective molecules. However, little is known about the behavior of these cardiomyocytes in simulated ischemia/reperfusion conditions. In this study, we have tested the cytoprotective effect of an NO donor and the brain type natriuretic peptide (BNP) in a screening platform based first on differentiated embryonic bodies (EBs, 6 + 4 days) and then on more differentiated cardiomyocytes (6 + 24 days), both derived from hESCs. Methods. Both types of hESC-derived cells were exposed to 150 min simulated ischemia, followed by 120 min reperfusion. Cell viability was assessed by propidium iodide staining. The following treatments were applied during simulated ischemia in differentiated EBs: the NO-donor S-nitroso-N-acetylpenicillamine (SNAP) (10−7, 10−6, and 10−5 M), BNP (10−9, 10−8, and 10−7 M), and the nonspecific NO synthase inhibitor Nω-nitro-L-arginine (L-NNA, 10−5 M). Results. SNAP (10−6, 10−5 M) significantly attenuated cell death in differentiated EBs. However, simulated ischemia/reperfusion-induced cell death was not affected by BNP or by L-NNA. In separate experiments, SNAP (10−6 M) also protected hESC-derived cardiomyocytes. Conclusions. We conclude that SNAP, but not BNP, protects differentiated EBs or cardiomyocytes derived from hESCs against simulated ischemia/reperfusion injury. The present screening platform is a useful tool for discovery of cardiocytoprotective molecules and their cellular mechanisms.

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Combined hypoxia and sodium nitrite pretreatment for cardiomyocyte protection in vitro

Cited by 12 publications

References 77 publications

In Vitro Models of Ischemia-Reperfusion Injury

In Vitro Models of Ischemia-Reperfusion Injury

Beyond Family: Modeling Non-hereditary Heart Diseases With Human Pluripotent Stem Cell-Derived Cardiomyocytes

Exogenous Nitric Oxide Protects Human Embryonic Stem Cell‐Derived Cardiomyocytes against Ischemia/Reperfusion Injury

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