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1.
Ann Med Surg (Lond) ; 86(7): 3880-3886, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38989172

ABSTRACT

Background: Syncope is a serious consequence in patients with hypertrophic obstructive cardiomyopathy (HOCM). Percutaneous endocardial septal radiofrequency ablation (PESA) has emerged as a promising intervention to alleviate symptoms and enhance the quality of life for HOCM patients. However, little is known about the effects of PESA on syncope in HOCM. The authors aimed to study the effects of PESA on syncope in patients with HOCM. Materials and methods: Nineteen patients with HOCM and syncope were enrolled. The left ventricular outflow tract gradient (LVOTG) of the patients was more than 50 mmHg despite medication. The participants underwent PESA under the guidance of intracardiac echocardiography (ICE) combined with a three-dimensional electrophysiological mapping system. The patients were followed for 3 (3-5.5) months. Results: The mean age of the patients was 54.8±13.7 years. Out of the 19 participants, 7 (37%) were females. During the follow-up, the syncope was completely alleviated in 14 patients (73.7%) or the syncope episodes were reduced greater than or equal to 80% in 16 patients (84.2%). The mean NYHA functional class significantly improved from 2.2±0.7 at baseline to 1.7±0.6 during follow-up (P=0.002). The LVOTG and septal thickness showed a decreasing trend from baseline to follow-up (LVOTG: P=0.083, septal thickness: P=0.086). Conclusion: The authors' investigation provides evidence supporting the effectiveness of PESA in reducing syncope episodes in patients with HOCM.

2.
Cell Death Differ ; 30(3): 825-838, 2023 03.
Article in English | MEDLINE | ID: mdl-36639542

ABSTRACT

Ischemic heart disease is a leading cause of death worldwide. Myocardial infarction (MI) results in cardiac damage due to cell death and insufficient cardiomyocyte self-renewal. Ferroptosis, a novel type of cell death, has recently been shown as a key cause of cardiomyocyte death after MI. However, the complicated regulation mechanisms involved in ferroptosis, especially how ferroptosis is integrated into classical cell survival/death pathways, are still unclear. Here, we discovered that HIP-55, a novel adaptor protein, acts as a hub protein for the integration of the ferroptosis mechanism into the classical AKT cell survival and MAP4K1 cell death pathways for MI injury. The expression of HIP-55 is induced in MI. Genetic deletion of HIP-55 increased cardiomyocyte ferroptosis and MI injury, whereas cardiac-specific overexpression of HIP-55 significantly alleviated cardiomyocyte ferroptosis and MI injury. Mechanistically, HIP-55 was identified as a new AKT substrate. AKT phosphorylates HIP-55 at S269/T291 sites and further HIP-55 directs AKT signaling to negatively regulate the MAP4K1 pathway against MI injury in a site-specific manner. S269A/T291A-mutated HIP-55 (HIP-55AA), which is defective in AKT phosphorylation and significantly decreases the interaction between HIP-55 and MAP4K1, failed to inhibit the MAP4K1/GPX4 ferroptosis pathway. In line with this mechanism, cardiac-specific overexpression of HIP-55WT mice, but not cardiac-specific overexpression of HIP-55AA mice, protected cardiomyocytes against MI-induced ferroptosis and cardiac injury in vivo. These findings suggest that HIP-55 rewired the classical AKT (cell survival) and MAPK (cell death) pathways into ferroptosis mechanism in MI injury. HIP-55 may be a new therapeutic target for myocardial damage.


Subject(s)
Ferroptosis , Myocardial Infarction , Mice , Animals , Proto-Oncogene Proteins c-akt/metabolism , Myocardial Infarction/metabolism , Signal Transduction , Cell Death , Adaptor Proteins, Signal Transducing/metabolism , Myocytes, Cardiac/metabolism
3.
Curr Med Res Opin ; 36(4): 545-546, 2020 04.
Article in English | MEDLINE | ID: mdl-31990218

ABSTRACT

Osteocalcin is an osteoblast-derived peptide mainly found in the bone matrix but also in circulation. A recent investigation suggested that osteocalcin mediated acute stress response (ASR) by inhibiting parasympathetic tone in mice and humans. We propose a hypothesis that osteocalcin is regulated by the skeleton movement and glucocorticoids, and inhibition of the parasympathetic tone by osteocalcin may indicate a therapeutic target in the treatment of acute myocardial infarction (AMI).


Subject(s)
Bone and Bones/physiology , Myocardial Infarction/physiopathology , Osteocalcin/physiology , Stress, Physiological/physiology , Acute Disease , Animals , Autonomic Nervous System/physiopathology , Heart Failure/physiopathology , Humans , Mice , Myocardial Infarction/drug therapy , Osteocalcin/blood
4.
J Nanosci Nanotechnol ; 19(12): 7546-7550, 2019 12 01.
Article in English | MEDLINE | ID: mdl-31196259

ABSTRACT

Excessive ß-adrenergic stimulation induces cardiac fibrosis and inflammation and eventually leads to heart failure. It remains unclear whether the inflammatory factor and infiltration of macrophages are initiated from cardiac cells or the vascular system. We used 13-nm polyethylene glycol (PEG)-coated gold nanoparticles (GNPs) as size probes because they cannot penetrate normal vascular walls, and we found that over-stimulation of ß-adrenoceptors mediates cardiac inflammation and fibrosis by increasing vascular permeability. Stimulation with isoproterenol (ISO, a ß-adrenoceptor agonist) induced tissue-specific inflammatory infiltration and fibrosis in the hearts of mice. Consistent with these findings, 13-nm PEG-coated GNP as size probes were also observed to have tissue-specific targeting of the fibrotic heart, indicating over-stimulation of ß-adrenoceptors, increased vascular permeability in the heart, and initiated cardiac inflammation and fibrosis.


Subject(s)
Gold , Metal Nanoparticles , Animals , Capillary Permeability , Fibrosis , Heart , Isoproterenol/pharmacology , Mice
5.
Can J Physiol Pharmacol ; 96(12): 1318-1327, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30383982

ABSTRACT

Gold nanoparticles (AuNPs) are widely used for drug delivery because of their unique biological properties, such as their safety and ability to prolong drug action. Some studies have demonstrated that AuNPs accumulate in the heart, especially during pathological processes. Therefore, it is very important to understand the effect of AuNPs on the heart. Myocardial infarction (MI) is a major cause of morbidity and mortality; however, the effect of AuNPs on MI remains unclear. In the present study, we carried out a comprehensive evaluation of AuNPs on acute MI. The results showed that AuNPs accumulated in infarcted hearts, decreased infarction size, improved systolic function, and inhibited cardiac fibrosis and TNF-α accumulation. Our work indicated that AuNPs have cardioprotective effects and can be used in drug delivery systems for the treatment of cardiac diseases.


Subject(s)
Gold/pharmacology , Heart/drug effects , Metal Nanoparticles/administration & dosage , Myocardial Infarction/drug therapy , Polyethylene Glycols/chemistry , Animals , Disease Models, Animal , Drug Delivery Systems/methods , Fibrosis/drug therapy , Male , Mice , Mice, Inbred BALB C
6.
Int J Nanomedicine ; 12: 4709-4719, 2017.
Article in English | MEDLINE | ID: mdl-28740379

ABSTRACT

Gold nanoparticles (AuNPs) are widely used as a drug delivery vehicle, which can accumulate in the heart through blood circulation. Therefore, it is very important to understand the effect of AuNPs on the heart, especially under pathological conditions. In this study, we found that PEG-coated AuNPs attenuate ß-adrenergic receptor (ß-AR)-mediated acute cardiac hypertrophy and inflammation. However, both isoproterenol, a non-selective ß-AR agonist, and AuNPs did not induce cardiac function change or cardiac fibrosis. AuNPs exerted an anti-cardiac hypertrophy effect by decreasing ß1-AR expression and its downstream ERK1/2 hypertrophic pathway. Our results indicated that AuNPs might be safe and have the potential to be used as multi-functional materials (drug carrier systems and anti-cardiac hypertrophy agents).


Subject(s)
Cardiomegaly/drug therapy , Nanoparticles/chemistry , Receptors, Adrenergic, beta/metabolism , Adrenergic beta-Agonists/pharmacology , Adrenergic beta-Agonists/toxicity , Animals , Cardiomegaly/metabolism , Fibrosis/chemically induced , Gold/pharmacokinetics , Gold/pharmacology , Heart/drug effects , Interleukin-6/genetics , Isoproterenol/toxicity , MAP Kinase Signaling System/drug effects , Male , Mice, Inbred Strains , Myocardium/metabolism , Nanoparticles/administration & dosage , Polyethylene Glycols/chemistry , Receptors, Adrenergic, beta/genetics , Receptors, Adrenergic, beta-1/metabolism
7.
Sci Rep ; 6: 20203, 2016 Feb 01.
Article in English | MEDLINE | ID: mdl-26830764

ABSTRACT

Gold nanoparticles (GNPs) are attracting more and more attention for their great potential value in biomedical application. Currently, no study has been reported on the chronic cardiac toxicity of GNPs after repeated administration. Here we carried out a comprehensive evaluation of the chronic cardiac toxicity of GNPs to the heart. Polyethylene glycol (PEG) -coated GNPs at three different sizes (10, 30 and 50 nm) or PBS was administrated to mice via tail vein for 14 consecutive days. Then the mice were euthanized at 2 weeks, 4 weeks or 12 weeks after the first injection. The accumulation of GNPs in the mouse heart and their effects on cardiac function, structure, fibrosis and inflammation were analysized. GNPs with smaller size showed higher accumulation and faster elimination. None of the three sizes of GNPs affected cardiac systolic function. The LVIDd (left ventricular end-diastolicinner-dimension), LVMass (left ventricular mass) and HW/BW (heart weight/body weight) were significantly increased in the mice receiving 10 nm PEG-GNPs for 2 weeks, but not for 4 weeks or 12 weeks. These results indicated that the accumulation of small size GNPs can induce reversible cardiac hypertrophy. Our results provide the basis for the further biomedical applications of GNPs in cardiac diseases.


Subject(s)
Cardiomegaly/pathology , Cardiomegaly/physiopathology , Gold , Metal Nanoparticles , Polyethylene Glycols , Animals , Biomarkers , Cardiomegaly/therapy , Coated Materials, Biocompatible , Cytokines/metabolism , Disease Models, Animal , Fibrosis , Gold/chemistry , Heart Function Tests , Inflammation/etiology , Inflammation/pathology , Inflammation Mediators/metabolism , Metal Nanoparticles/administration & dosage , Metal Nanoparticles/chemistry , Metal Nanoparticles/ultrastructure , Mice , Models, Biological , Myocardium/metabolism , Myocardium/pathology , Particle Size , Polyethylene Glycols/chemistry
8.
Beijing Da Xue Xue Bao Yi Xue Ban ; 47(6): 893-7, 2015 Dec 18.
Article in Chinese | MEDLINE | ID: mdl-26679646

ABSTRACT

OBJECTIVE: To further demonstrate the interaction of a new 14-3-3 interaction protein hematopoietic progenitor kinase 1[HPK1]-interacting protein (HIP-55) and 14-3-3 proteins and its potential biological function in HEK293 cells. METHODS: PDEST-N-Venus-HIP-55WT (wild type),PDEST-N-Venus-HIP-55AA (mutants, S269A/T291A, abolishing the binding of HIP-55 to 14-3-3),PDEST-GST-HIP-55WT and PDEST-C-Venus-14-3-3τ plasmids were constructed by gateway system. Their expressions were demonstrated by Western blotting method. Then we used Bimolecular Fluorescence Complementation (BiFC) and co-immunoprecipitation (co-IP) methods to demonstrate the interaction of HIP-55 and 14-3-3 in HEK293 cells. Moreover, the 14-3-3 antagonist peptide, R18 and HIP-55 protein mutant plasmid HIP-55AA were used to detect the protein synthesis of HIP-55 at different time points induced by puromycin, an inhibitor of protein production. RESULTS: The HEK293 cells expressed HIP-55 protein respectively, after being transected with PDEST-N-Venus-HIP-55WT,PDEST-N-Venus-HIP-55AA,PDEST-GST-HIP-55WT plasmids and expressed 14-3-3 protein after being transected with PDEST-C-Venus-14-3-3τ plasmids. We could detect venus fluorescence of venus-HIP-55 protein via confocal microscopy in HEK 293 cells transfected with N-Venus-HIP-55 and C-14-3-3τ plasmids by BiFC, but not in HEK 293 cells transfected with N-Venus-HIP-55 AA (mutants S269A/T291A) and C-14-3-3τ plasmids. The results of BiFC suggested that 14-3-3 interacted with HIP-55 through HIP-55 S269/T291 sites. At the same time, the data of co-IP showed that there were endogenous interactions between 14-3-3 and HIP-55. Furthermore, puromycin had no influence in HIP-55 protein synthesis at hours 0, 4, or 8 in HEK 293 cells expressing GST-HIP-55WT and 14-3-3 plasmids, while puromycin blocked HIP-55 protein synthesis in HEK 293 cells transfected with N-Venus-HIP-55AA (mutants S269A/T291A) and C-14-3-3τ plasmids. The results indicated that the 14-3-3/HIP-55 complex could contributed to the stability of HIP-55. CONCLUSION: HIP-55 forms a complex with 14-3-3 and 14-3-3/HIP-55 interaction increases the stability of HIP-55.


Subject(s)
14-3-3 Proteins/chemistry , Microfilament Proteins/chemistry , Blotting, Western , HEK293 Cells , Humans , Microscopy, Confocal , Microscopy, Fluorescence , Plasmids , Protein Biosynthesis , Protein Stability , Puromycin/chemistry , Transfection , src Homology Domains
9.
Sheng Li Ke Xue Jin Zhan ; 46(2): 81-6, 2015 Apr.
Article in Chinese | MEDLINE | ID: mdl-26201103

ABSTRACT

Vascular diseases has become a top killer of human health, and cardiovascular receptors are pivotal in the occurrence, development, prevention and treatment of cardiovascular diseases. As for the important member of G protein-coupled receptor, ß-adrenergic receptor is undoubtedly a most important target of cardiovascular drugs. Being the hot spot in the cardiovascular research and application, ß- adrenergic receptor blocker has been considered as the greatest breakthrough for the prevention and cure of cardiovascular disease after digitalis. The 2012 Nobel Prize in chemistry was awarded again to the researchers on ß-adrenergic receptors. Extensive researchs show that ß-adrenergic receptors are precisely regulated by different regulatory proteins in cells in the transduction of different physiological and pathological signaling pathways. Based on these findings, function-selective ligands recently arise in the receptor research and will be the new chance of drug discovery. In this article we reviewed the related signal pathways and functions of ß-adrenergic receptor regulatory proteins.


Subject(s)
Receptors, Adrenergic, beta/metabolism , Cardiovascular Diseases , Cardiovascular System , Humans , Ligands , Signal Transduction
10.
Br J Pharmacol ; 172(23): 5573-85, 2015 Dec.
Article in English | MEDLINE | ID: mdl-25766073

ABSTRACT

BACKGROUND AND PURPOSE: Cardiac fibrosis is a common feature of advanced coronary heart disease and is characteristic of heart disease. However, currently available drugs against cardiac fibrosis are still very limited. Here, we have assessed the role of isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxylpropanoate (IDHP), a new metabolite of Danshen Dripping Pills, in cardiac fibrosis mediated by the ß-adrenoceptor agonist, isoprenaline, and its underlying mechanisms. EXPERIMENTAL APPROACH: Identification of IDHP was identified by mass spectrometry, and proton and carbon nuclear magnetic resonance spectra. Myocardial collagen was quantitatively assessed with Picrosirius Red staining. Expression of mRNA for collagen was evaluated with real-time PCR. Phosphorylated and total p38 MAPK, NADPH oxidase (NOX) and superoxide dismutase (SOD) were analysed by Western blot. Generation of reactive oxygen species (ROS) generation was evaluated by dihydroethidium (DHE) fluorescent staining. NOX2 was knocked down using specific siRNA. KEY RESULTS: IDHP attenuated ß-adrenoceptor mediated cardiac fibrosis in vivo and inhibited isoprenaline-induced proliferation of neonatal rat cardiac fibroblasts (NRCFs) and collagen I synthesis in vitro. Phosphorylation of p38 MAPK, which is an important mediator in the pathogenesis of isoprenaline-induced cardiac fibrosis, was inhibited by IDHP. This inhibition of phospho-p38 by IDHP was dependent on decreased generation of ROS. These effects of IDHP were abolished in NRCFs treated with siRNA for NOX2. CONCLUSIONS AND IMPLICATIONS: IDHP attenuated the cardiac fibrosis induced by isoprenaline through a NOX2/ROS/p38 pathway. These novel findings suggest that IDHP is a potential pharmacological candidate for the treatment of cardiac fibrosis, induced by ß-adrenoceptor agonists.


Subject(s)
Drugs, Chinese Herbal/pharmacology , Fibrosis/drug therapy , Heart Failure/drug therapy , Membrane Glycoproteins/metabolism , NADPH Oxidases/metabolism , Propionates/pharmacology , Reactive Oxygen Species/metabolism , Salvia miltiorrhiza/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism , Animals , Animals, Newborn , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/metabolism , Drugs, Chinese Herbal/therapeutic use , Fibroblasts/drug effects , Fibroblasts/metabolism , Fibrosis/chemically induced , Fibrosis/metabolism , Heart/drug effects , Heart Failure/chemically induced , Heart Failure/metabolism , Injections, Subcutaneous , Isoproterenol/pharmacology , Male , NADPH Oxidase 2 , Phosphorylation/drug effects , Propionates/administration & dosage , Propionates/metabolism , Propionates/therapeutic use , Rats , Rats, Sprague-Dawley , Salvia miltiorrhiza/chemistry , Signal Transduction/drug effects , Structure-Activity Relationship
11.
FASEB J ; 29(6): 2495-503, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25690657

ABSTRACT

Actin and dynamin work cooperatively to drive the invagination and scission of clathrin-coated pits (CCPs). However, little is known about the mechanism that orchestrates the spatiotemporal recruitment of dynamin and actin. Here, we have identified the mammalian actin-binding protein 1 (mAbp1; also called HIP-55 or SH3P7), which could bind to clathrin, actin, as well as dynamin, as an adaptor that links the dynamic recruitment of dynamin and actin for the scission of CCPs. Live-cell imaging reveals that mAbp1 is specifically recruited at a late stage of the long-lived CCPs. mAbp1 knockdown impaired CCP scission by reducing dynamin recruitment at the plasma membrane. However, actin disruption remarkably eliminates mAbp1 recruitment and thus dynamin recruitment. These data suggest that by binding to both clathrin and F-actin, mAbp1 is specifically recruited at a late stage of CCP formation, which subsequently recruits dynamin to CCPs.


Subject(s)
Actins/metabolism , Clathrin/metabolism , Coated Pits, Cell-Membrane/metabolism , Dynamins/metabolism , Microfilament Proteins/metabolism , Animals , Cell Line, Tumor , Clathrin/genetics , Coated Pits, Cell-Membrane/ultrastructure , Dynamins/genetics , Humans , Immunoblotting , Luminescent Proteins/genetics , Luminescent Proteins/metabolism , Mice , Microfilament Proteins/genetics , Microscopy, Electron, Transmission , Microscopy, Fluorescence/methods , NIH 3T3 Cells , Protein Binding , Time-Lapse Imaging/methods , src Homology Domains/genetics
12.
Biol Pharm Bull ; 37(6): 961-7, 2014.
Article in English | MEDLINE | ID: mdl-24882408

ABSTRACT

Danshensu, the effective ingredient of the plant Salvia miltiorrhiza (Danshen), has been widely used for treatment of cardiovascular diseases. Cardiac fibrosis is an important process in pathological cardiac remodeling and leads to heart failure. We investigated the effect of Danshensu on ß-adrenergic receptor (ß-AR)-mediated cardiac fibrosis and the involved signaling transduction. Danshensu inhibited cardiofibroblast proliferation and collagen I synthesis induced by isoproterenol (ISO), a selective ß-AR agonist. Phosphorylation of p38 mitogen-activated protein kinase (MAPK), which mediates ISO-induced cardiac fibrosis, was negatively regulated in this process. The negative regulation depended on the ISO inhibition of reactive oxygen species (ROS) production. Taken together, Danshensu may inhibit ß-AR-mediated cardiac fibrosis by negative regulation of ROS-p38 MAPK signaling.


Subject(s)
Cardiomyopathies/pathology , Cardiomyopathies/prevention & control , Lactates/pharmacology , MAP Kinase Signaling System/drug effects , Reactive Oxygen Species/metabolism , Receptors, Adrenergic, beta/metabolism , Adrenergic beta-Agonists/pharmacology , Animals , Cardiomyopathies/enzymology , Cardiomyopathies/metabolism , Cell Proliferation/drug effects , Cells, Cultured , Collagen Type I/biosynthesis , Fibroblasts/drug effects , Fibroblasts/pathology , Fibrosis , Isoproterenol/pharmacology , Lactates/administration & dosage , Lactates/therapeutic use , Rats, Sprague-Dawley
13.
Mol Biosyst ; 10(7): 1932-9, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24802081

ABSTRACT

The activation of ß-adrenergic receptors (ß-ARs) plays a key role in regulating cardiac function. However, the detailed regulatory mechanisms of ß-AR-induced fibrosis are still unclear. We used a proteomics approach to analyze the changes in protein expression patterns in cardiac fibrosis with ß-AR stimulation. HIP-55 (also called debrin-like; DBNL) was revealed as a novel regulator in the signaling regulatory network with ß-AR activation. Further studies of both HIP-55-overexpressed and -deficient cardiac fibroblasts indicated that HIP-55 negatively regulated ß-AR-activated cardiac fibroblast proliferation and the proliferative signaling pathway may be associated with the extracellular signal-regulated protein kinase (ERK) activation. Our data provide a new mechanistic insight into the role of HIP-55 in ß-AR-induced cardiac fibroblast proliferation and suggest a new treatment strategy for proliferative disorders.


Subject(s)
Heart Injuries/pathology , Microfilament Proteins/metabolism , Proteomics/methods , Receptors, Adrenergic, beta/metabolism , Animals , Animals, Newborn , Cell Proliferation , Cells, Cultured , Fibroblasts/metabolism , Fibrosis/chemically induced , Gene Expression Regulation/drug effects , Heart Injuries/chemically induced , Isoproterenol/adverse effects , MAP Kinase Signaling System/drug effects , Microfilament Proteins/genetics , Rats , Rats, Sprague-Dawley , src Homology Domains/genetics
14.
Mol Biosyst ; 10(6): 1393-9, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24668193

ABSTRACT

HIP-55 (hematopoietic progenitor kinase 1 [HPK1]-interacting protein of 55 kDa) is the mammalian homologue of the yeast Abp1p. It contains a C-terminal Src homology 3 domain and an N-terminal actin depolymerization factor (ADF-H/C) domain. HIP-55 appears to be critical for organ development and immune response and is important for the regulation of the actin cytoskeleton through its interactions with F-actin and various cytoskeletal and cell signaling proteins. However, the function of HIP-55 in tumors remains unknown. Here, we found that HIP-55 is up-regulated or down-regulated in several types of tumor tissues in patients. Of these, lung cancer tissues had the highest expression of HIP-55. To gain full insight into the function of HIP-55 in lung cancer, microarray assay was performed using Affymetrix U133 Plus 2.0 expression arrays in both HIP-55 knockdown and scramble control A549 cells. The ingenuity pathway analysis tool was utilized to construct biological networks and analyze functions that might be associated with HIP-55. Functional analysis strongly suggested that HIP-55 may be involved in cancer cell survival and cell death, which was then confirmed by further experimentation. Experimental results showed that downregulation of HIP-55 decreased the viability and increased the apoptosis of A549 cells treated with the anticancer agent etoposide. Our data suggested that HIP-55 may be a newly discovered regulatory node in the growth signaling network and a new target for therapeutic interventions in proliferative disorders.


Subject(s)
Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Microfilament Proteins/metabolism , Signal Transduction , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Carcinoma, Non-Small-Cell Lung/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Etoposide/pharmacology , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Humans , Lung Neoplasms/metabolism , Protein Array Analysis , Signal Transduction/drug effects , Tissue Array Analysis , src Homology Domains
15.
Toxicol Lett ; 222(2): 197-203, 2013 Oct 24.
Article in English | MEDLINE | ID: mdl-23906719

ABSTRACT

In this study, we investigated the cardiac biodistribution of polyethylene glycol (PEG)-coated AuNPs and their effects on cardiac function, structure and inflammation in both normal and cardiac remodeling mice. The model of cardiac remodeling was induced by subcutaneously injection of isoproterenol (ISO), a non-selective beta-adrenergic agonist, for 7 days. After AuNPs were injected intravenously in mice for 7 consecutive days, Au content in different organs was determined quantitatively by inductively coupled plasma mass spectrometry (ICP-MS), cardiac function and structure were measured by echocardiography, cardiac fibrosis was examined with picrosirius red staining, the morphology of cardiomyocytes was observed with hematoxylin and eosin (H & E) staining. The accumulation of AuNPs in hearts did not affect cardiac function or induce cardiac hypertrophy, cardiac fibrosis and cardiac inflammation under normal physiological condition. Cardiac AuNPs content was 6-fold higher in the cardiac remodeling mouse than normal mice. However, the increased accumulation of AuNPs in the heart did not aggravate ISO-induced cardiac hypertrophy, cardiac fibrosis or cardiac inflammation. These observations suggest that PEG-coated AuNPs possess excellent biocompatibility under both physiological and pathological conditions. Thus, AuNPs may be safe for cardiac patients and hold great promise for further development for various biomedical applications.


Subject(s)
Gold/adverse effects , Heart Ventricles/drug effects , Metal Nanoparticles/adverse effects , Ventricular Function/drug effects , Adrenergic beta-Agonists , Animals , Cardiomegaly/chemically induced , Cardiomegaly/immunology , Cardiomegaly/pathology , Cardiomegaly/physiopathology , Cardiotoxins/adverse effects , Disease Models, Animal , Drug Delivery Systems , Fibrosis , Gold/analysis , Gold/pharmacokinetics , Heart Ventricles/cytology , Heart Ventricles/immunology , Heart Ventricles/pathology , Isoproterenol , Male , Metal Nanoparticles/chemistry , Metal Nanoparticles/ultrastructure , Mice , Mice, Inbred BALB C , Polyethylene Glycols/adverse effects , Random Allocation , Surface Properties , Tissue Distribution , Ventricular Remodeling/drug effects
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