PLGA‐PNIPAM Microspheres Loaded with the Gastrointestinal Nutrient NaB Ameliorate Cardiac Dysfunction by Activating Sirt3 in Acute Myocardial Infarction

Cheng, Panke; Zeng, Wen; Li, Li; Huo, Da; Le, Zeng; Tan, Ju; Zhou, Jingting; Sun, Jun; Liu, Ge; Li, Yanzhao; Guan, Ge; Wang, Yuxin; Zhu, Chuhong

doi:10.1002/advs.201600254

Cited by 22 publications

(18 citation statements)

References 38 publications

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“…AMI is a major cause of morbidity and mortality worldwide and needs to be addressed urgently [ 12 ]. Apoptosis and necrosis are 2 pivotal events of AMI, which are known to play important roles during the process [ 13 , 14 ]. Myocardial apoptosis is followed by necrosis, which occurs during sustained and severe ischemia, and it is an unregulated irreversible response to a fatal challenge which usually involves myocardial pump failure [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Knockdown of MicroRNA-122 Protects H9c2 Cardiomyocytes from Hypoxia-Induced Apoptosis and Promotes Autophagy

Zhang¹,

Li²,

Chen³

et al. 2017

Med Sci Monit

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BackgroundAcute myocardial infarction (AMI) is a severe disease causing heart failure and sudden death. Studies indicate that microRNAs (miRNAs) are involved in the pathophysiology of AMI. In the present study, we carefully explored the effects of miR-122 on myocardial hypoxia injury and its possible underlying mechanism.Material/MethodsmiR-122 expression was analyzed in H9c2 cardiomyocytes after being transfected with miR-122 mimic, ASO-miR-122, or negative control. Cell viability and apoptosis were investigated by CCK-8 assays and flow cytometry analysis, respectively. Cell migration was analyzed using wound-healing assays. Western blotting was performed to analyze the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/phosphatidylinositol 3-hydroxy kinase (PI3K)/AKT and LC3-II/LC3-I.ResultHypoxia exposure significantly inhibited H9c2 cell viability (P<0.01). miR-122 overexpression promoted the hypoxia-induced H9c2 cell proliferation and migration loss (P<0.05), and cell apoptosis was increased (P<0.05). miR-122 knockdown enhanced cell viability and decreased cell apoptosis (P<0.05). Knockdown of miR-122 enhanced PTEN/PI3K/AKT activation and cell autophagy. Overexpression of miR-122 inhibited the PTEN/PI3K/AKT pathway and cell autophagy pathway.ConclusionsThe expression of miR-122 is involved in hypoxia-induced H9c2 cardiomyocyte injury. Knockdown of miR-122 protects H9c2 cells from hypoxia-induced apoptosis and enhances cell viability.

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Section: Discussionmentioning

confidence: 99%

Knockdown of MicroRNA-122 Protects H9c2 Cardiomyocytes from Hypoxia-Induced Apoptosis and Promotes Autophagy

Zhang¹,

Li²,

Chen³

et al. 2017

Med Sci Monit

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“…Increased acetylation of the ETC complexes correlates with a reduction in catalytic activity, impaired mitochondrial oxidative phosphorylation and consequently compromised contractile function of the heart. Therefore, approaches that upregulate and/or maintain SIRT3 expression and activity may represent a promising therapeutic strategy to treat or prevent cardiac dysfunction in the setting of MI [ 41 , 43 , 44 ]. In agreement with these reports, the current study demonstrated that the preserved SIRT3 activity in both sEH null mice or t AUCB pre-treated females subjected to MI correlates with enhanced cardiac contractile function compared to WT counterparts.…”

Section: Discussionmentioning

confidence: 99%

Soluble Epoxide Hydrolase in Aged Female Mice and Human Explanted Hearts Following Ischemic Injury

Jamieson

Darwesh

Sosnowski

et al. 2021

IJMS

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Myocardial infarction (MI) accounts for a significant proportion of death and morbidity in aged individuals. The risk for MI in females increases as they enter the peri-menopausal period, generally occurring in middle-age. Cytochrome (CYP) 450 metabolizes N-3 and N-6 polyunsaturated fatty acids (PUFA) into numerous lipid mediators, oxylipids, which are further metabolised by soluble epoxide hydrolase (sEH), reducing their activity. The objective of this study was to characterize oxylipid metabolism in the left ventricle (LV) following ischemic injury in females. Human LV specimens were procured from female patients with ischemic cardiomyopathy (ICM) or non-failing controls (NFC). Female C57BL6 (WT) and sEH null mice averaging 13–16 months old underwent permanent occlusion of the left anterior descending coronary artery (LAD) to induce myocardial infarction. WT (wild type) mice received vehicle or sEH inhibitor, trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (tAUCB), in their drinking water ad libitum for 28 days. Cardiac function was assessed using echocardiography and electrocardiogram. Protein expression was determined using immunoblotting, mitochondrial activity by spectrophotometry, and cardiac fibre respiration was measured using a Clark-type electrode. A full metabolite profile was determined by LC–MS/MS. sEH was significantly elevated in ischemic LV specimens from patients, associated with fundamental changes in oxylipid metabolite formation and significant decreases in mitochondrial enzymatic function. In mice, pre-treatment with tAUCB or genetic deletion of sEH significantly improved survival, preserved cardiac function, and maintained mitochondrial quality following MI in female mice. These data indicate that sEH may be a relevant pharmacologic target for women with MI. Although future studies are needed to determine the mechanisms, in this pilot study we suggest targeting sEH may be an effective strategy for reducing ischemic injury and mortality in middle-aged females.

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“…In summary, netrin‐1‐modified small‐diameter TEBVs can get early inflammation resolution, which contributes to homing EPCs survival and quick endothelialization. Additionally, patients who need small‐diameter TEBVs often have the disease like diabetes or atherosclerosis, so we need further study the inflammatory condition and resolution ways of small‐diameter TEBVs in these disease state.…”

Section: Discussionmentioning

confidence: 99%

Netrin‐1 Promotes Inflammation Resolution to Achieve Endothelialization of Small‐Diameter Tissue Engineering Blood Vessels by Improving Endothelial Progenitor Cells Function In Situ

Wan

Liu

et al. 2017

Advanced Science

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The transplant of small‐diameter tissue engineering blood vessels (small‐diameter TEBVs) (<6 mm) in vascular replacement therapy often fails because of early onset thrombosis and long‐standing chronic inflammation. The specific inflammation state involved in small‐diameter TEBVs transplants remains unclear, and whether promoting inflammation resolution would be useful for small‐diameter TEBVs therapy need study. The neural protuberant orientation factor 1 (Netrin‐1) is found present in endothelial cells of natural blood vessels and has anti‐inflammatory effects. This work generates netrin‐1‐modified small‐diameter TEBVs by using layer‐by‐layer self‐assembly to resolve the inflammation. The results show that netrin‐1 reprograms macrophages (MΦ) to assume an anti‐inflammatory phenotype and promotes the infiltration and subsequent efflux of MΦ from inflamed sites over time, which improves the local microenvironment and the function of early homing endothelial progenitor cells (EPCs). Small‐diameter TEBVs modified by netrin‐1 achieve endothelialization after 30 d and retain patency at 14 months. These findings suggest that promoting the resolution of inflammation in time is necessary to induce endothelialization of small‐diameter TEBVs and prevent early thrombosis and problems associated with chronic inflammation. Furthermore, this work finds that the MΦ‐derived exosomes can target and regulate EPCs, which may serve as a useful treatment for other inflammatory diseases.

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PLGA‐PNIPAM Microspheres Loaded with the Gastrointestinal Nutrient NaB Ameliorate Cardiac Dysfunction by Activating Sirt3 in Acute Myocardial Infarction

Cited by 22 publications

References 38 publications

Knockdown of MicroRNA-122 Protects H9c2 Cardiomyocytes from Hypoxia-Induced Apoptosis and Promotes Autophagy

Knockdown of MicroRNA-122 Protects H9c2 Cardiomyocytes from Hypoxia-Induced Apoptosis and Promotes Autophagy

Soluble Epoxide Hydrolase in Aged Female Mice and Human Explanted Hearts Following Ischemic Injury

Netrin‐1 Promotes Inflammation Resolution to Achieve Endothelialization of Small‐Diameter Tissue Engineering Blood Vessels by Improving Endothelial Progenitor Cells Function In Situ

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