Left ventricle transcriptomic analysis reveals the initial decline in VO2peak from its lifetime apex associates with connective tissue accumulation
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 2500
ORGANISM(S): Rattus norvegicus
SUBMITTER: Tom Childs
PROVIDER: E-MTAB-5223 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Purpose: Aerobic capacity is a strong predictor of cardiovascular mortality. To determine the relationship between inborn aerobic capacity and soleus gene expression we examined genome-wide gene expression in soleus muscle of rats artificially selected for high and low running capacity (HCR and LCR, respectively) over 16 generations. The artificial selection of LCR caused accumulation of risk factors of cardiovascular disease similar to the metabolic syndrome seen in man, whereas HCR had markedly better cardiac function. We also studied alterations in gene expression in response to exercise training in the two groups, since accumulating evidence indicates that exercise has profound beneficial effects on the metabolic syndrome. Methods:; Soleus gene expression of both sedentary and exercise trained HCR and LCR was characterized by microarray- and gene ontology analysis. Results: Although HCR and LCR had an inborn 347% difference in running capacity, only three genes were found differentially expressed in the soleus muscle between the two groups. Up-regulation of the mitochondrial enzyme leucyl-transferRNA synthetase (LARS2) was found in the sedentary LCR. Increased expression of LARS2 has been associated with a mitochondrial DNA mutation linked to maternally inherited diabetes and mitochondrial dysfunction. In line with our findings, a growing body of evidence suggests that LCR have compromised mitochondrial function. After exercise training, 58 genes were altered in the soleus muscle of HCR, in contrast to only one in the LCR group. This suggests that animals born with different levels of fitness respond different to the same type of exercise training. Adaptations to exercise in HCR seemed to be associated with increased lipid metabolism and fatty acid elongation in the mitochondria. Also, genes associated with the peroxisomes, seemed to be central in the adaptation to exercise. Conclusion: The results indicate that (i) LCR might have mitochondrial dysfunction, which may be a contributing factor of the low inborn aerobic capacity, (ii) animals born with different levels of fitness respond different to the same exercise program. Experiment Overall Design: There are 16 samples in this study.
2008-06-18 | E-GEOD-10527 | biostudies-arrayexpress
Project description:Dahl salt-sensitive (DS) rats were obtained from Harlan Sprague Dawley Laboratory at 5 weeks of age. At 6 weeks of age, physiologic cardiac hypertrophy was generated by a; vigorous daily exercise regimen for 6 weeks (e group). The exercise protocol is based on those described previously with modifications (Wisloff U et al., 2001; Jin H et al., 1994). Rats were exercised daily for 6 weeks on a rodent treadmill (Exer-6M; Columbus Instruments). The exercise program consisted of three weeks of progressively strenuous exercise regimens; followed by three weeks of maintenance period, during which the rats were exercised at 16 m/min at a 5o incline for 90 minutes/day. All rats completed the exercise protocol. Pathological cardiac hypertrophy was generated by feeding a 6% NaCl diet to DS rats at 6 weeks of age (h group) (Inoko M et al., 1994). Control rats (c group) were age matched and sedentary DS rats fed normal rat chow. Read more at http://cardiogenomics.med.harvard.edu/groups/proj1/pages/rat_home.html<br><br>Note that files GSM11886.txt and GSM12308.txt, and files GSM11887.txt and GSM12309.txt as downloaded from GEO contain identical data.
2007-10-11 | E-GEOD-776 | biostudies-arrayexpress
Project description:Gene expression data at rest and immediately post 30 min submaximal exercise in 3 month and 16 month old male rats, some of which were sedentary (SED), had access to a physical activity box twice weekly (PA) and some of which had daily access to a running wheel (EX). We used microarrays to detail global gene expression underlying select health-related phenotypes and identified differentially expressed genes among the three groups. Young (3 month) and old (16 month) male rats were separated into three different groups: Sedentary (SED), twice-weekly physical activity (PA), and regular exercise (EX). Animals were sacrificed either at rest or after 30 min of sub maximal exercise. Then, a portion of cardiac tissue was collected for RNA extraction and hybridization on Affymetrix microarrays.
2013-10-18 | E-GEOD-51380 | biostudies-arrayexpress
Project description:We used high density oligonucleotide arrays to measure the relative expression levels of ~27,000 probe sets in the left ventricles of inbred rat strains; DA (high performing), Copenhagen (COP, low performing), as well as F1(COPxDA) rats bred from these tw
2007-09-13 | E-GEOD-1795 | biostudies-arrayexpress
Project description:Exercise improves brain function enhancing neuronal plasticity and cognitive enhancement. For voluntary resistance wheel running (RWR) exercise, with a load of 30% of body weight, we reported enhancement of neurogenesis and spatial memory associated with hippocampal brain-derived neurotrophic factor (BDNF) signaling compared to wheel running (WR) without a load (Lee et al., 2012; Lee et al., 2013). Despite these new evidences, mechanisms for RWR-induced improvement of hippocampal function remained to be clarified. In the present study, we have utilized the high-throughput DNA microarray approach to gain deep insight into molecular mechanisms underlying these changes that could be novel targets of RWR-induced hippocampal plasticity. To do so, whole genome (4x44K) high-density oligonucleotide microarrays were used to monitor the expression level of gene transcripts in the hippocampus of rats voluntary running for 4 weeks in comparison with sedentary animals. These rats showed a significant decrease in average running distance although average work levels immensely increased 12-fold in the RWR group, resulting in muscular adaptation for the fast-twitch plantaris muscle. DNA microarray analysis revealed that 122 (sedentary x WR) and 157 (sedentary x RWR) genes were up-regulated (> 1.5-fold change) as compared with 97 (sedentary x WR) and 467 (sedentary x RWR) down-regulated genes (< 0.75-fold change). Functional categorization using the Ingenuity Pathway Analysis (IPA) revealed expression pattern changes in the major categories of disease and disorders, molecular functions and physiological system development and function. Among these, RWR up-regulated genes such as NFATc1, AVPR1A and FGFR4, which are crucial role for neuronal development and its functions. The down-regulated inflammatory cytokines (IL1B, IL10, IL2RA, TNF) and chemokines (CXCL1, CXCL9, CXCL10, CCL2, CCL13, CCR4) might be important to neuronal dysfunction and vulnerability. Taken together, these gene candidates are suggested to play a critical role in hippocampal plasticity. This is a first study presenting not only new information into the voluntary RWR influenced transcriptome in the rat hippocampus, but also provides a hypothesis for the RWR influenced enhancement in brain function. 10-week-old male Wistar rats were randomly allocated to three groups: (1) housed in standard cages and used as non-active controls (sedentary, n = 10), (2) wheel running with no resistance (WR, n = 8), and (3) housed in cages with resistance running wheels with an adjustable resistance (RWR, n = 8). Rats of both running wheel groups (WR and RWR) were housed individually and had free access to a specially designed running wheel apparatus for 24 h/day. Between 08:00 and 12:00 on the day after the final day of exercise, the animals were immediately decapitated using a guillotine. The hippocampi were rapidly dissected, snap frozen in liquid nitrogen and stored at —80°C prior to further analysis. The deep-frozen hippocampi were transferred to a precooled (in liquid nitrogen) mortar and ground with a pestle to a very fine powder with liquid nitrogen. Total RNA was extracted and validated followed by checking subsequently synthesized cDNA by RT-PCR. A rat 4x44K whole genome oligo DNA microarray chip was used for global gene expression analysis using the hippocampi. Fluorescently labeled targets of Sed, WR and RWR samples were hybridized to the same microarray slide with 60-mer probes. A flip labeling (dye swap or reverse labeling with Cy3 and Cy5 dyes) procedure was followed to nullify the dye bias associated with unequal incorporation of the two Cy dyes into cDNA. Briefly, to select differentially expressed genes, we identified genes that were up regulated in chip 1 (Cy3/Cy5 label for sedentary and WR, respectively) but down regulated in chip 2 (Cy3/Cy5 label for WR and sedentary, respectively) for the hippocampus. The same selection criteria were applied for chips 3-4 (sedentary and RWR). Hybridization and wash processes were performed according to the manufacturer’s instructions, and hybridized microarrays were scanned using an agilent microarray scanner. The functional and network analysis were generated through the use of IPA (Ingenuity® Systems, www.ingenuity.com). To validate gene changes in array data and test the BDNF signaling-related molecules and expression of select transcripts were determined by quantitative real-time RT-PCR.
2014-10-09 | E-GEOD-52516 | biostudies-arrayexpress
Project description:Seventy two rats were randomized to twelve independent groups of rats (n = 6 in all groups) where half of the rats were chosen for training (treadmill exercise training 1.5 hour 5 days a week, in 1, 4, 24, 48 days and for 4 and 8 weeks) or sedentary (no training) as described in detail by Wisloff et al. (Intensity-controlled treadmill running in rats: VO(2 max) and cardiac hypertrophy. Am J Physiol Heart Circ Physiol. 2001 Mar;280(3):H1301-10.) or Kemi et al.(Aerobic fitness is associated with cardiomyocyte contractile capacity and endothelial function in exercise training and detraining. Circulation. 2004 Jun 15;109(23):2897-904. Epub 2004 Jun 1.). The rats were scarified one hour after training (1, 4, 24 and 48 days) or 24 hours after training (4 and 8 weeks). Biopsies form left ventricle was taken form all rats and stored on -80°C for preparation of RNA. The same procedures were performed for the control/sedentary rats which were sacrificed at the same time as the exercised rats.
2006-11-10 | E-TABM-166 | biostudies-arrayexpress
Project description:substantial number of people at risk to develop type 2 diabetes could not improve insulin sensitivity by physical training intervention. We studied the mechanisms of this impaired exercise response in 20 middle-aged individuals who performed a controlled eight weeks cycling and walking training at 80 % individual VO2max. Participants identified as non-responders in insulin sensitivity (based on Matsuda index) did not differ in pre-intervention parameters compared to high responders. The failure to increase insulin sensitivity after training correlates with impaired up-regulation of mitochondrial fuel oxidation genes in skeletal muscle, and with the suppression of the upstream regulators PGC1α and AMPKα2. The muscle transcriptome of the non-responders is further characterized by an activation of TGFβ and TGFβ target genes, which is associated with increases in inflammatory and macrophage markers. TGFβ1 as inhibitor of mitochondrial regulators and insulin signaling is validated in human skeletal muscle cells. Activated TGFβ1 signaling down-regulates the abundance of PGC1α, AMPKα2, mitochondrial transcription factor TFAM, and of mitochondrial enzymes. Thus, increased TGFβ activity in skeletal muscle can attenuate the improvement of mitochondrial fuel oxidation after training and contribute to the failure to increase insulin sensitivity. We performed gene expression microarray analysis on muscle biopsies from humans before and after an eight weeks endurance training intervention
2016-06-29 | E-GEOD-72462 | biostudies-arrayexpress
Project description:Many studies have reported on beneficial aspects of running to improve hippocampus-related spatial memory and promote neuroplastic changes like adult hippocampal neurogenesis (AHN). Such research has also revealed molecular factors associated with molecular signaling by BDNF and IGF-I leading to CREB activation. However, the optimum exercise intensity for genome-wide beneficial effects remains unclear. We thus investigate the whole spectrum of hippocampal molecular change by exercise using DNA microarray-based transcript profiling in two different intensity groups. Lactate threshold (LT), at which lactate starts to accumulate in the blood, defined the intensity: mild- (ME, <LT) or intense-exercise (IE, >LT). Rats were subjected to 6 weeks of training or sedentary (CONT) regimes. After 6 weeks, spatial memory using Morris Water Maze (MWM), AHN, and hippocampal gene expressions were assessed. The functional relationships among the differentially expressed genes were generated using Ingenuity Pathway Analysis and QIAGEN-based pathway analysis. Results revealed that ME, but not IE, improved the performance on probe trial in MWM and increased newborn mature neurons (BrdU+/NeuN+ cells) compared with CONT. Transcript profiling by comparison with CONT postulated that ME regulated protein synthesis through IRS-dependent pathway (e.g. PI3K-Akt signaling cascade), cholesterol trafficking and perisynaptic environment, while IE induced dysfunction of these process and cell death. The comparison of the expression between each intensity also supported these tendencies. Collectively, our findings indicate mild exercise should be beneficial in the development of both enhanced AHN and spatial memory, and several genes related to protein synthesis and lipid-metabolism may be critical those neuroplastic changes. This study is the first step to identify the potential triggers of exercise-induced cognitive gain. Eleven-week-old male Wistar rats (220-270 g; SLC, Saitama, Japan) were housed in polycarbonate steel cages with a 12-h light/dark schedule (lights on at 7:00 a.m.) and given ad libitum access to food and water. A total of 98 rats were used in this study to assess the influence of exercise intensity on physiological states (training effect of skeletal muscle and stress level) (n= 22), MWM (n= 32), AHN (n= 22), and global gene expression profiles of hippocampal by microarray (n= 22). All animal care and experimental procedures were performed in accordance with protocols approved by the University of Tsukuba Animal Experiment Committee, based on the National Institute of Health (NIH) Guidelines for the Care and Use of Laboratory Animals (NIH publication, revised 1996). All efforts were made to minimize animal suffering and to reduce the number of animals used in this study. To adapt the rearing environment and remove any unintended stress effects, animals underwent a week of preliminary rearing to ambient conditions in groups housing conditions (2-3 rats/cage). After the preliminary rearing, the animals were randomized into three groups based on the LT of treadmill running: Sedentary control (CONT, rest on treadmill), Mild Exercise (ME, below LT, 15 m/min) or Intense Exercise (IE, above LT, 40 m/min). Exercise group was habituated to run on a treadmill (KN-73, Natsume Ltd., Tokyo, Japan) for 1 (for ME) or 4 (for IE) weeks. Within a given test period, rats were able to run on the above-mentioned running speeds. After this running habituation, rats were entered into the exercise training session for 6 weeks in total. The running duration was 60 min/day and frequency was 5 times/week. Exercise training was performed between 19:00 and 22:00 (during dark phase). Rat’s body weight and physical condition were monitored until the end of training. If rats could not perform well running on each determined speed and showed poor health, those were eliminated from the study. Based on the criteria, a total of 13 rats were eliminated (bad runner - 4 rats; poor health - 7 rats). Twenty-four or thirty-six hours after the last training, rats were processed to the next step. In the microarray group, the whole brain of each animal was rapidly removed, and hippocampus was separated on ice according to the method of Glowinski and Iversen (1966), with minor modifications. Hippocampi were immediately flash-frozen in liquid nitrogen. The deep-frozen hippocampi were transferred to a pre-chilled (in liquid nitrogen) mortar and pestle, and ground to a very fine powder with liquid nitrogen. The powdered samples were stored in aliquots at -80ºC till used for further analysis. Total RNA was extracted from each sample powder (~50 mg) using the QIAGEN RNeasy Mini Kit (QIAGEN, Maryland, USA). To verify the quality of this RNA, the yield and purity were determined spectrophotometrically (NanoPhotomaterTM, IMPLEN, Munich, Germany) and visually confirmed using formaldehyde gel electrophoresis. We used the sample with a ratio of spectrophotometric absorbance at 260 nm to that at 230 (A260/A230) or 280 nm (A260/A280) above 1.8. An equal amount of RNA (1000 ng) from the five rats, randomly picked up from each exercise group (n = 5), was pooled and used for microarray analysis. In this study, we performed three combinations of comparison analysis of gene expression change. First, we compared the difference between CONT and ME (combination 1) or IE (combination 2) to confirm the exercise-intensity-dependent gene expression change. Subsequently, we made a comparison of ME with IE (combination 3) to elucidate a ME-based difference of IE inducible gene. In all combinations, total RNA (1000 ng) was labeled with either Cy3 or Cy5 dye using an Agilent Low RNA Input Fluorescent Linear Amplification Kit (Agilent Technologies Inc., CA, USA). Fluorescently labeled targets of control as well as treated samples were hybridized to the same microarray slide with 60-mer probes (4 x 44K (41,090 gene probes), rat whole genome, Agilent). A flip labelling (dye-swap or reverse labelling with Cy3 and Cy5 dyes) procedure was followed to nullify the dye bias associated with unequal incorporation of the two Cy dyes into cDNA. Hybridization and wash processes were performed according to the manufacturer’s instructions, and hybridized microarrays were scanned using an Agilent Microarray scanner. For the detection of significantly differentially expressed genes between control and exercise samples each slide image was processed by Agilent Feature Extraction software (version 9.5.3.1).
2014-04-05 | E-GEOD-45813 | biostudies-arrayexpress
Project description:n total, 16 7-week-old male F344 rats were subjected to model regular exercise and sedentary lifestyle. In the second week after arrival and acclimatization to the reversed light/dark cycle, rats were introduced to the forced running wheel without a specific running mode. It was followed by a 12-day training phase for all 16 experimental animals (started at 9 weeks of age) by gradually increasing the running speed and duration. During the training phase, 8 best performers were selected for the runner group while the remaining 8 rats were assigned to the sedentary group. The regular forced running exercise phase for the runner group lasted for 5 weeks in total, including 4 weeks of regular running. After 4 weeks of regular exercise, rats underwent brief anesthesia and of blood from the tail vein were taken. This step was repeated for the same animals immediately after 1h of running. On the same day, a blood sample was collected from the sedentary rats following the same protocol. Plasma was collected and immediately frozen for further EV isolation. EVs were isolated from rat plasma by size exclusion chromatography. RNA libraries were constructed using CleanTag® Small RNA Library Prep Kit (Trilink Biotechnologies, USA) and sequenced on Illumina NextSeq500 instrument using NextSeq 500/550 Mid Output Kit v2.5 (150 cycles).
2021-12-28 | E-MTAB-11020 | biostudies-arrayexpress
Project description:This analysis was done to determine which muscle group has the most skeletal muscle transcriptional reponses to wheel running activity. Seven male mice with C57BL/6 genetic background were placed individually in cages with running wheels and allowed free access to the wheels 24 hr per day. Access to running wheels began when the mice were 6 months old, and continued for 12 weeks. The morning after the night of running, the mice were euthanized and several muscle groups were snap froze in liquid nitrogen to preserve RNA. The same muscle groups were collected from three age-matched "sedentary" mice that were housed in ordinary cages that did not permit sustained running. For each muscle group, separate pools of polyadenylated RNA from the sedentary and wheel-running mice were prepared for deep sequencing of cDNA with the SOLiD 3 platform. Four muscle groups were examined (quadriceps femoris; gastrocnemius/plantaris; tibialis anterior; triceps brachii). For each muscle, RNA was pooled from 3 sedentary or 7 wheel-running mice (8 pools total).
2011-09-03 | E-GEOD-31843 | biostudies-arrayexpress