Asiatic acid enhances survival of human AC16 cardiomyocytes under hypoxia by upregulating miR‐1290

Wu, Kai; Hu, Min; Chen, Zejin; Xiang, Feixiang; Chen, Guojian; Wang, Yan; Peng, Qing; Chen, Xiaoping

doi:10.1002/iub.1648

Cited by 25 publications

(17 citation statements)

References 38 publications

(54 reference statements)

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“…These cells are differentiated following transfer into mitogen-depleted media that stops their proliferation, and they express cardiac-specific proteins and maintain cardiac nuclear and mitochondrial DNA. AC16 cardiomyocytes have been used and validated in an in vitro study that examined the effect of asiatic acid of IRI [59]. The results were consistent with other studies in a rat model and an in vitro H9c2 cardiomyoblast model that also demonstrated asiatic acid attenuation of IRI [60, 61].…”

Section: In Vitro Models Of Irisupporting

confidence: 64%

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 Irisupporting

confidence: 64%

In Vitro Models of Ischemia-Reperfusion Injury

Chen

Vunjak-Novakovic

2018

Regen. Eng. Transl. Med.

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“…As for miR-1290, it was predominantly reported to act in tumor progression [ 65 , 66 ]. In addition, it has been demonstrated that the upregulated miR-1290 in non-small-cell lung cancer A549 cells could attenuate ischemia/reperfusion induced myocardial apoptosis [ 71 ]. Hence miR-1290 may be able to enhance the vascularization of ECs.…”

Section: Discussionmentioning

confidence: 99%

Bioglass enhances the production of exosomes and improves their capability of promoting vascularization

2021

Bioactive Materials

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Recently, exosomes have been extensively applied in tissue regeneration. However, their practical applications are severely restricted by the limited exosome secretion capability of cells. Therefore, developing strategies to enhance the production of exosomes and improve their biological function attracts great interest. Studies have shown that biomaterials can significantly enhance the paracrine effects of cells and exosomes are the main signal carriers of intercellular paracrine communication, thus biomaterials are considered to affect the exosome secretion of cells and their biological function. In this study, a widely recognized biomaterial, 45S5 Bioglass® (BG), is used to create a mild and cell-friendly microenvironment for mesenchymal stem cells (MSCs) with its ion products. Results showed that BG ion products can significantly improve exosome production of MSCs by upregulating the expression of neutral sphingomyelinase-2 (nSMase2) and Rab27a which enhanced the nSMases and Rab GTPases pathways, respectively. Besides, microRNA analysis indicates that BG ion products can modulate the cargoes of MSCs-derived exosomes by decreasing microRNA-342-5p level while increasing microRNA-1290 level. Subsequently, the function of exosomes is modified as their capabilities of promoting the vascularization of endothelial cells and facilitating the intradermal angiogenesis are enhanced. Taken together, BG ion products are confirmed to enhance exosome production and simultaneously improve exosome function, suggesting a feasible approach to improve the practical application of exosomes in regenerative medicine.

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“…Firstly, based on the versatile activities of AA, our model may only partially explain its protective effect against hepatic I/R. Previous studies have shown that AA acted to regulate various downstream pathways such as Nrf2, AMPK, mTOR, Akt/GSK-3β/HIF-1α and miR-1290/HIF3A/HIF-1α, among many others [ 42 , 54 - 56 ]. Given that most of these pathways are critically involved in I/R, it is probable that AA may mediate hepatoprotection through these pathways besides PPARγ/NLRP3 axis.…”

Section: Discussionmentioning

confidence: 99%

Asiatic acid protects against hepatic ischemia/reperfusion injury by inactivation of Kupffer cells via PPARγ/NLRP3 inflammasome signaling pathway

et al. 2017

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Hepatic ischemia/reperfusion (I/R) contributes to major complications in clinical practice affecting perioperative morbidity and mortality. Recent evidence suggests the key role of nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammaosme activation on the pathogenesis of I/R injury. Asiatic acid (AA) is a pentacyclic triterpene derivative presented with versatile activities, including antioxidant, anti-inflammation and hepatoprotective effects. This study was designed to determine whether AA had potential hepatoprotective benefits against hepatic I/R injury, as well as to unveil the underlying mechanisms involved in the putative effects. Mice subjected to warm hepatic I/R, and Kupffer cells (KCs) or RAW264.7 cells challenged with lipopolysaccharide (LPS)/H2O2, were pretreated with AA. Administration of AA significantly attenuated hepatic histopathological damage, global inflammatory level, apoptotic signaling level, as well as NLRP3 inflammasome activation. These effects were correlated with increased expression of peroxisome proliferator-activated receptor gamma (PPARγ). Conversely, pharmacological inhibition of PPARγ by GW9662 abolished the protective effects of AA on hepatic I/R injury and in turn aggravated NLRP3 inflammasome activation. Activation of NLRP3 inflammasome was most significant in nonparenchymal cells (NPCs). Depletion of KCs by gadolinium chloride (GdCl3) further attenuated the detrimental effects of GW9662 on hepatic I/R as well as NLRP3 activation. In vitro, AA concentration-dependently inhibited LPS/H2O2-induced NLRP3 inflammaosome activation in KCs and RAW264.7 cells. Either GW9662 or genetic knockdown of PPARγ abolished the AA-mediated inactivation of NLRP3 inflammasome. Mechanistically, AA attenuated I/R or LPS/H2O2-induced ROS production and phosphorylation level of JNK, p38 MAPK and IκBα but not ERK, a mechanism dependent on PPARγ. Finally, AA blocked the deleterious effects of LPS/H2O2-induced macrophage activation on hepatocyte viability in vitro, and improved survival in a lethal hepatic I/R injury model in vivo. Collectively, these data suggest that AA is effective in mitigating hepatic I/R injury through attenuation of KCs activation via PPARγ/NLRP3 inflammasome signaling pathway.

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Asiatic acid enhances survival of human AC16 cardiomyocytes under hypoxia by upregulating miR‐1290

Cited by 25 publications

References 38 publications

In Vitro Models of Ischemia-Reperfusion Injury

In Vitro Models of Ischemia-Reperfusion Injury

Bioglass enhances the production of exosomes and improves their capability of promoting vascularization

Asiatic acid protects against hepatic ischemia/reperfusion injury by inactivation of Kupffer cells via PPARγ/NLRP3 inflammasome signaling pathway

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