Gene expression profiles of hexadecyl-4-124I-iodobenzoate(124I-HIB)-labeled adipose-derived stem cells (ADSCs) in vitro and in vivo
ABSTRACT:  Microarray analysis in the rat myocardial tissue: 124I-HIB transplanted MI model Vs. phosphate buffered saline (PBS) injected myocardial infarction (MI) model Vs. Sham operated model  Microarray analysis in the rat adipose derived stem cells: 124I-HIB-labeled ADSCs Vs. Unlabeled ADSCs  We investigated the change of gene expression profile in sham operated-, PBS injected- and 124I-HIB-labeled ADSCs transplanted myocardium in rat myocaridial infarction (MI) model.  We compared gene expression profile with 124I-HIB labeled ADSCs and unlabeled ADSCs in vitro.
Project description:The use of cDNA microarrays has made it possible to analyze expression of thousands of genes simultaneously. We employed microarray gene expression profiling of porcine cDNA to compare myocardial gene expression in infarct core and remote myocardium at 1 week (n=3), 4 weeks (n=3), and 6 weeks (n=3) after surgically induced myocardial infarction (MI) and in sham-operated controls (n=3). More than 8,000 cDNA sequences were identified in myocardium that showed differential expression in response to MI. Different temporal and spatial patterns of gene expression were recognized in the infarct core tissue within this large set of data. Microarray gene profiling revealed candidate genes, some of them described for the first time, which elucidate changes in biological processes at different stages after MI. We evaluated temporal gene expression in a porcine model of myocardial infarction by microarray technology. Nine female pigs (Sus scrofa crossbreed Landrace x Large White) weighing 30-40 kg were subjected to experimental MI by a double-ligation of the first marginal branch of the circumflex artery. Animals were randomly sacrificed at 1 week (n=3), 4 weeks (n=3), or 6 weeks (n=3) after MI. Three paired myocardial samples from the infarct core and remote myocardium were analyzed at each time point. Myocardial samples from sham-operated animals (open-chest cardiac exposure without coronary artery ligation; n=3) were included as physiological controls.
Project description:Myocardial Infarction Model: Sixty nine animals (252 ± 2 g) were randomized to either myocardial infraction (MI) or sham operation. MI were produced by partial ligation of the left coronary artery as described in detail by Loennechen et al. (Loennechen JP, Stoylen A, Beisvag V, Wisloff U, Ellingsen O: Regional expression of endothelin-1, ANP, IGF-1, and LV wall stress in the infarcted rat heart. Am J Physiol Heart Circ Physiol 2001, 280: H2902-H2910.). Animals with large infarctions (45 ± 2% of LV) were euthanized on one of the following days: day 1 (n = 6), 3(n = 5), 7 (n = 6), 14 (n = 6), 42 (n =6) and 91 (n = 4); and sham-operated animals were euthanized on one of the following days: 1 (n = 6), 3(n = 6), 7 (n = 6), 14 (n = 6), 42 (n =6) and 91 (n = 6). After sacrifice, heart tissue was removed, weighted and scored for size of the healed infarction. Infarct size was measured and the left ventricular myocardium stored on -80°C for preparation of RNA.
Project description:Myocardial infarction (MI) often results in left ventricular (LV) remodeling followed by heart failure (HF). It is of great clinical importance to understand the molecular mechanisms that trigger transition from compensated LV injury to HF and to identify relevant diagnostic biomarkers. In this study, we performed transcriptional profiling of LVs in rats with a wide range of experimentally induced infarct sizes and of peripheral blood mononuclear cells (PBMCs) in animals that developed HF. We used microarrays to investigate gene expression in the left ventricle (LV) accompanying myocardial infarction and concomitant heart failure (HF) in a well validated model of post-infarcted heart failure and to evaluate their reflection in peripheral blood mononuclear cells (PBMCs) Myocardial infarction (MI) was induced in male Wistar rats by ligation of the proximal left coronary artery. The sham-operated group (control group) was subjected to the same protocol, except that the suture was not tied around the proximal left coronary artery. Sham-operated rats (n=6) and rats with small (n=6), moderate (n=6), and large (n=5) MI size were included into the experiment two months after the operation. Then, left ventricules and blood samples were obtained for RNA extraction and hybridization on Affymetrix microarrays. Microarrays were used to compare the LV and PBMCs transcriptomes of control and experimental animals. The development of heart failure was estimated by echocardiography and catheterization.
Project description:In order to examine the mechanism of TPO on cardiac protection against myocardial infarction damage (MI), we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to delineate the TPO cardioprotective mechanism against infarction. MI and TPO induced gene expressions in rat heart were measured at week 4. Two biological replicates were performed for each treatment group.
Project description:In order to examine the mechanism of TPO on cardiac protection against myocardial infarction damage (MI), we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to delineate the TPO cardioprotective mechanism against infarction. Overall design: MI and TPO induced gene expressions in rat heart were measured at week 4. Two biological replicates were performed for each treatment group.
Project description:A microarray-based screening was conducted in rat hearts 24 hours after myocardial infarction (MI) with the aim to discover yet unknown molecules that might have an impact on cardiac pathophysiology.
Project description:We have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to influence the pathogenesis after myocardial infarction. Male mice (8 weeks old) were anesthetized and subjected to permanent occlusion of the left coronary artery [Myocardial infarction (MI) model]. Overall design: Gene expression in wild-type mouse heart was measured at 3 days after the MI-surgery.
Project description:Comparison of both LncRNAs and mRNAs expression in the border zone of the myocardial infarction rats and the sham operation rats Border zone (BZ) of the myocardial infarction is critical to patients. Current treatments of myocardial infarction are primarily aimed to save the dying myocardial cell in the border zone. During myocardial infarction, certain changes in BZ, e.g, apoptosis, fibrosis, inflammation, etc, played an important role in deciding the survival. Impairment and recovery of BZ has been linked to gene expression changes. The aim of our study was to obtain a global expression profile of lncRNAs and mRNAs of the border zone in Wistar rats myocardial infarction, and identify the changes during myocardial infarction. Overall design: 3 male rats were used to set up myocardial infarction model by ligation of LAD, and 3 rats were sham-operated. Border zone tissue of myocardial infarction was determined by TTC&EB double stain, then was send to further microarry analysis.
Project description:Thyroid hormone improves left ventricular remodeling and cardiac performance after myocardial infarction (MI), but the molecular basis is unknown. This study was designed to detect gene expression changes in left ventricular non-infarcted areas at 4 weeks following myocardial infarction with and without thyroid hormone treatment. The results suggest that altered expression of genes for molecular function and biological process may be involved in the beneficial effects of thyroid hormone treatment following myocardial infarction in rats. MI was produced by ligation of the left anterior descending coronary artery in female SD rats. Rats were divided into the following groups: (1) Sham MI, (2) MI, and (3) MI+T4 treatment (T4 pellet 3.3mg, 60 days release, implanted subcutaneously immediately following MI). Four weeks after surgery, total RNA was isolated from left ventricular non-infarcted areas for microarray analysis using the Illumina RatRef-12 Expression BeadChip Platform.
Project description:In this study, we used a cardiac-specific, inducible expression system to activate YAP in adult mouse heart. Activation of YAP in adult heart promoted cardiomyocyte proliferation and did not deleteriously affect heart function. Furthermore, YAP activation after myocardial infarction (MI) preserved heart function and reduced infarct size. Using adeno-associated virus subtype 9 (AAV9) as a delivery vector, we expressed human YAP in the murine myocardium immediately after MI. We found that AAV9:hYAP significantly improved cardiac function and mouse survival. AAV9:hYAP did not exert its salutary effects by reducing cardiomyocyte apoptosis. Rather, we found that AAV9:hYAP stimulated adult cardiomyocyte proliferation. Gene expression profiling indicated that AAV9:hYAP stimulated cell cycle gene expression, enhanced TGFβ-signaling, and activated of components of the inflammatory response.Cardiac specific YAP activation after MI mitigated myocardial injury after MI, improved cardiac function and mouse survival. These findings suggest that therapeutic activation of hYAP or its downstream targets, potentially through AAV-mediated gene therapy, may be a strategy to improve outcome after MI. Three groups were involved in this study: sham group, AAV9:Luci+MI group and AAV9-YAP+MI group. Each group contained three biological replicates. The sham group had neither myocardial infarction nor AAV injection. The AAV9:Luci +MI(L for brief) group had myocardial infarction and injected with AAV9:Luic. The AAV9:hYAP+MI(YAP for brief) group had myocardial infarction and injected with AAV9:hYAP. 5 days after MI and AAV injection, the heart apexes were collected and the total RNA were isolated for microarray analysis.