ABSTRACT: This dataset is a time series (1 hour [h], 4 hours, 24 hours, 48 hours, 1 week [w], and 8 weeks) intended to compare normal functioning left ventricles [lv + lv2] with infarcted [ilv] and non-infarcted left ventricles [nilv]. Ilv samples are taken from the region between the LAD artery and the apex on a mouse with myocardial infarction. Lv2 samples are from the same region in a sham operated mouse. Nilv samples are taken from the region above the infartion and the left ventricle [lv] samples mimic that region in a sham mouse. The lv and lv2 samples can be compared as both are from normal functioning hearts. For more information visit http://cardiogenomics.med.harvard.edu/groups/proj1/pages/mi_home.html Keywords: other
Project description:This dataset is a time series (1 hour [h], 4 hours, 24 hours, 48 hours, 1 week [w], and 8 weeks) intended to compare normal functioning left ventricles [lv + lv2] with infarcted [ilv] and non-infarcted left ventricles [nilv]. ilv samples are taken from the region between the LAD artery and the apex on a mouse with myocardial infarction. Lv2 samples are from the same region in a sham operated mouse. Nilv samples are taken from the region above the infartion and the left ventricle [lv] samples mimic that region in a sham mouse. The lv and lv2 samples can be compared as both are from normal functioning hearts. For more information visit http://cardiogenomics.med.harvard.edu/groups/proj1/pages/mi_home.html
Project description:We analyzed time dependent global proteomic adaptations during heart failure (HF) progression in a mouse model, suffering from left ventricular pressure overload due to transverse aortic constriction (TAC), to gain deeper insights in the disease development and identify new biomarker candidates. The hearts from TAC and sham mice were examined by cardiac MRI on either day 4, 14, 21, 28, 42, and 56 after surgery (n=6 group/time point). At each time point, proteomes of the left (LV) and right ventricles (RV) of TAC and sham mice were analyzed by mass spectrometry (MS).
Project description:Myocardial infarction (MI) is the leading cause for hear failure (HF). Following MI, the non-infarcted region of left ventricle (LV) is critical for maintaining heart function, and disruption of the LV contributes greatly to post-MI HF. Transcriptomic profiling by high-throughput sequencing was performed in a chronic HF pig model, to explore the molecular changes in the post-MI LV related to cardiovascular deterioration. Samples were taken from heart tissue of MI-induced pigs and from control pigs not subjected to MI. Regions of the heart where samples were taken included the site of ischemia (LV ischemia), area bordering ischemia (LV border), area remote to ischemia (LV remote) and the right ventricle (RV).
Project description:We created a fetal lamb model of hypoplastic left heart syndrome (HLHS), by implanting coils in the left atrium in mid-gestation. We performed bulk RNA sequencing of left ventricles (LV), right ventricles (RV), ascending aortae (AAo) and pulmonary arteries (PA). Single nucleus RNA sequencing was performed on LV free wall tissue (n = 4 coiled samples, n = 3 controls).
Project description:We created a fetal lamb model of hypoplastic left heart syndrome (HLHS), by implanting coils in the left atrium in mid-gestation. We performed bulk RNA sequencing of left ventricles (LV), right ventricles (RV), ascending aortae (AAo) and pulmonary arteries (PA). Single nucleus RNA sequencing was performed on LV free wall tissue (n = 4 coiled samples, n = 3 controls).
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:We compare microarray data from homogenized left ventricles of the heart at 24 hours after sham surgey vs 8-min potassium chloride induced sudden cardiac arrest and resuscitation
Project description:We report a genome-wide survey of early responses of the mouse heart transcriptome to acute myocardial infarction (AMI). For three regions of the left ventricle (LV), namely ischemic/infarcted tissue (IF), the surviving LV free wall (FW) and the interventricular septum (IVS), 36,899 transcripts were assayed at six time points from 15 min to 48 h post-AMI in both AMI and sham surgery mice. For each transcript, temporal expression patterns were systematically compared between AMI and sham groups, which identified 515 AMI-responsive genes in IF tissue, 35 in the FW, 7 in the IVS, with three genes induced in all three regions. Using the literature, we assigned functional annotations to all 519 nonredundant AMI-induced genes and present two testable models for central signaling pathways induced early post-AMI. First, the early induction of 15 genes involved in assembly and activation of the activator protein-1 (AP-1) family of transcription factors implicates AP-1 as a dominant regulator of earliest post-ischemic molecular events. Second, dramatic increases in transcripts for arginase 1 (ARG1), the enzymes of polyamine biosynthesis and protein inhibitor of nitric oxide synthase (NOS) activity indicates that NO production may be regulated, in part, by inhibition of NOS and coordinate depletion of the NOS substrate, L-arginine. ARG1 was the single most highly induced transcript in the database (121-fold in IF region) and its induction in heart has not been previously reported. Keywords: heart attack, mouse, time course, regional responses We report temporal and regional changes in steady state mRNA levels in the mouse LV following a surgically-induced AMI. Three regions of the infarcted LV were surveyed: IF, FW and IVS. For each region, mRNA levels were assayed at t=0 and six time points after occlusion of the left anterior descending coronary artery (t = 15 min, 1 h, 4 h, 12 h, 24 h, 48 h). As control, an identical time course was carried out in the mouse LV after sham surgery in which the suture was passed under the artery, but not ligated. For sham surgical mice and naïve mice (t=0), the IVS and the LV free wall were harvested and assayed. The AMI and sham time courses were repeated for a total of two independent repetitions of the experiment. For each repetition, 96 GeneChips were hybridized. Thus, for two repetitions, 192 GeneChips (2 x 96) were hybridized. In addition, the naïve time point was assayed a second time during Repetition 1 for six additional GeneChips (two tissues x three chips). The overall total number of samples is 198 GeneChips (192 + 6). Total RNA was isolated from each individual tissue sample. Equal weights of total RNA from 4-10 mice were combined for each LV region, time point and treatment. Copy RNA mixtures were synthesized from each total RNA pool and hybridized to the Affymetrix GeneChip set MG U74 v2 (A, B, and C) that carries 36,899 probe sets. The global normalization of fluorescence emissions for the 198 GeneChips used in this study and their conversion to relative transcript concentrations measured in relative fluorescence units (RFU) was conducted using Robust Multi-array Averaging (RMA; www.bioconductor.org). Each of the 198 Accessions is titled as follows: time point / treatment / tissue, repetition, GeneChip. The additional assays of naïve mice in Repetition 1 are labeled “Naive2”.
Project description:We analyzed global proteomic adaptations during heart failure (HF) progression in a mouse model, suffering from left ventricular pressure overload due to transverse aortic constriction (TAC) and in response to riociguat (RIO) treatment, to gain deeper insights in beneficial effects due to sGC stimulation on cardiac remodeling and HF. TAC and sham animals were treated with either riociguat (RIO; 3 mg/kg/day) or vehicle (VEH; Transcutol®/Cremophor®/water: 10%/20%/70%) for five weeks, starting three weeks post-op when cardiac hypertrophy was established, resulting in four treatment groups ( n=5-6 per group). At the end of the study, hearts were dissected and proteomes of the left ventricles (LV) were analyzed by mass spectrometry (MS).
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.