The effect of Sulfonulyrea short form (SUR2A-55) overexpression on cardiac gene expression
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE245038 | GEO | 2023/10/16
REPOSITORIES: GEO
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Project description:Background: Demographic studies have shown that the mean age of patients requiring coronary artery bypass surgery (CABG) is 68 years with approximately 44% of these patients being female . In recent studies, women have been shown to have a significantly greater operative risk as compared to men and that women have worse outcomes after cardiac surgery. Recently we have shown that cardioprotection afforded by cardioplegia is modulated by RNA and protein dependent mechanisms and is significantly decreased with age and in particular is significantly decreased in the aged female. Methods: The mechanisms through which cardioplegia affords cardioprotection are complex and can not be investigated as a single entity but rather must be investigated using a systems approach. To meet these needs we have used microarray and proteomic analysis. The combined use of these two techniques allows for the identification of functionally related gene groups and protein biomarkers. Mature 15 to 20 weeks; 3 to 4 kg) and aged (not senescent, >32 months; 5 to 6 kg) male and female New Zealand White rabbits were used for in situ blood perfused cardiopulmonary bypass. Control hearts received 30 minutes sham ischemia and 120 minutes sham reperfusion. Global ischemia (GI) hearts received 30 minutes of global ischemia. GI was achieved by crossclamping of the aorta. Cardioplegia hearts received cold blood cardioplegia (Deaconess Surgical Associates (DSA) solution (containing 50 uM diazoxide) prior to GI. Following 30 minutes of GI the crossclamp was released, the cardiopulmonary bypass was ceased and the hearts were reperfused for 120 minutes. The hearts were removed flushed of blood and then quick frozen in liquid nitrogen prior to isolation of RNA and protein. Microarray and high throughput proteomic analysis was performed as previously described. Results: Our studies demonstrate that the cardioprotection afforded by cardioplegia is modulated by RNA and protein dependent mechanisms. Our data also show that there are significant differences in the proteins expressed in the mature and aged. Principal component analysis indicated that in the mature male, mature female, and aged male the proteins expressed in control, global ischemia, and cardioplegia were diverse and clustered for individual treatments suggesting that the proteins had different expression levels in each treatment. In contrast, in the aged female the proteins expressed in global ischemia and in cardioplegia were clustered together, suggesting there was no difference in the proteins expressed during global ischemia and with cardioplegia. Glycolysis/gluconeogensis was a significant functional pathway for the aged male but not the mature male or female. Glycolytic and gluconeogenic proteins were significantly up-regulated in the aged male compared to the female and significantly up-regulated in the aged male with cardioplegia as compared to global ischemia. In the aged female 9 unique mitochondrial proteins were up-regulated with cardioplegia. These proteins were associated with oxidative phosphorylation, the electron transport chain, the formation of pyruvate, and the tricarboxylic acid (TCA) cycle, but not glycolysis nor gluconeogenesis. Conclusions: Our study demonstrates that the mitochondrion plays a key role in age and gender specific cardioprotection. The identification of these specific pathways and biomarkers should allow for the development of age and gender specific cardioprotection and significantly decrease morbidity and mortality in the aged female. Rabbit heart (atria and ventricles):control vs. global ischemia; control vs. cardioplegia; cardioplegia vs. global ischemia
2011-06-28 | E-GEOD-30261 | biostudies-arrayexpress
Project description:Background: Demographic studies have shown that the mean age of patients requiring coronary artery bypass surgery (CABG) is 68 years with approximately 44% of these patients being female . In recent studies, women have been shown to have a significantly greater operative risk as compared to men and that women have worse outcomes after cardiac surgery. Recently we have shown that cardioprotection afforded by cardioplegia is modulated by RNA and protein dependent mechanisms and is significantly decreased with age and in particular is significantly decreased in the aged female. Methods: The mechanisms through which cardioplegia affords cardioprotection are complex and can not be investigated as a single entity but rather must be investigated using a systems approach. To meet these needs we have used microarray and proteomic analysis. The combined use of these two techniques allows for the identification of functionally related gene groups and protein biomarkers. Mature 15 to 20 weeks; 3 to 4 kg) and aged (not senescent, >32 months; 5 to 6 kg) male and female New Zealand White rabbits were used for in situ blood perfused cardiopulmonary bypass. Control hearts received 30 minutes sham ischemia and 120 minutes sham reperfusion. Global ischemia (GI) hearts received 30 minutes of global ischemia. GI was achieved by crossclamping of the aorta. Cardioplegia hearts received cold blood cardioplegia (Deaconess Surgical Associates (DSA) solution (containing 50 uM diazoxide) prior to GI. Following 30 minutes of GI the crossclamp was released, the cardiopulmonary bypass was ceased and the hearts were reperfused for 120 minutes. The hearts were removed flushed of blood and then quick frozen in liquid nitrogen prior to isolation of RNA and protein. Microarray and high throughput proteomic analysis was performed as previously described. Results: Our studies demonstrate that the cardioprotection afforded by cardioplegia is modulated by RNA and protein dependent mechanisms. Our data also show that there are significant differences in the proteins expressed in the mature and aged. Principal component analysis indicated that in the mature male, mature female, and aged male the proteins expressed in control, global ischemia, and cardioplegia were diverse and clustered for individual treatments suggesting that the proteins had different expression levels in each treatment. In contrast, in the aged female the proteins expressed in global ischemia and in cardioplegia were clustered together, suggesting there was no difference in the proteins expressed during global ischemia and with cardioplegia. Glycolysis/gluconeogensis was a significant functional pathway for the aged male but not the mature male or female. Glycolytic and gluconeogenic proteins were significantly up-regulated in the aged male compared to the female and significantly up-regulated in the aged male with cardioplegia as compared to global ischemia. In the aged female 9 unique mitochondrial proteins were up-regulated with cardioplegia. These proteins were associated with oxidative phosphorylation, the electron transport chain, the formation of pyruvate, and the tricarboxylic acid (TCA) cycle, but not glycolysis nor gluconeogenesis. Conclusions: Our study demonstrates that the mitochondrion plays a key role in age and gender specific cardioprotection. The identification of these specific pathways and biomarkers should allow for the development of age and gender specific cardioprotection and significantly decrease morbidity and mortality in the aged female.
2011-06-28 | GSE30261 | GEO
Project description:Simple Markov model.
There are 3 disease states: Healthy, Sick, and Dead, where the Dead state is terminal.
The yearly transition probabilities are:
Healthy to Dead: 0.01; Healthy to Sick: 0.2 for Male and 0.1 for Female; Sick to Healthy: 0.1; Sick to Dead: 0.3.
The transition probability now depends on the cohort (Male or Female) and can be expressed as a function of a Boolean covariate Male.
Initial conditions: Healthy = (50 Male, 50 Female), Sick = (0,0) and Dead = (0,0).
Output: Number of men and women in each disease state for years 1-10.
2019-01-30 | MODEL1803120004 | BioModels
Project description:Hearts were collected from Pcyt2+/- male and female mice at 8 months of age The microarray approach allows the investigation of gene expression changes of all genes in Pcyt2+/- male and female hearts.
2017-02-17 | GSE95010 | GEO
Project description:Hearts were collected from Pcyt2+/- male and female mice at 8 months of age The microarray approach allows the investigation of gene expression changes of all genes in Pcyt2+/- male and female hearts.
2022-02-08 | GSE166342 | GEO
Project description:Recent data from our group, demonstrate that infusion of myelin oligodendrocyte glycoprotein (MOG35-55) peptide, leads to induction of MOG35-55-specific Tregs and subsequent suppression of Experimental Autoimmune Encephalomyelitis (EAE), the mouse model of multiple sclerosis. Amelioration of EAE was accompanied by reduced MOG-specific Th1 and Th17 responses in the draining lymph nodes (dLNs). Phenotypic analysis of the dLNs of MOG-infused mice revealed a significant Treg-mediated reduction in the recruitment of 7AAD-CD3-CD19-CD11c+CD11bhighGr-1+ iDCs compared to non-infused control immunized mice. Focusing on the delineation of novel molecules/genes that are involved in the MOG-specific Treg-mediated suppression of autoimmune responses, we have isolated highly purified iDCs from MOG infused and non-infused control immunized mice.
2015-04-20 | GSE47210 | GEO
Project description:Analysis of the effects of aging on the development of dilated cardiomyopathy by characterizing both changes in ejection fraction (EF) and gene expression profile in 3 groups of male mice: Control (Cont or WT, n=11) and transgenic (Tg or KO) mice with either high EF (KO-H or Tg-H, n=7) or low EF (KO-L or Tg-L, n=6). We previously produced a line of transgenic mice (Tg) on a mixed genetic background where cardiac-specific overexpression of Cre recombinase reduced expression of the EP4 receptor gene. There were no obvious phenotypes in 10-12-week-old male Tg mice. To determine if a cardiac phenotype developed in aged mice, we assessed cardiac structure and function by echocardiography, histology and gene expression in 23-33-week-old male Tg and littermates (Cont). After echocardiography, hearts were removed to assess hypertrophy (MCSA), fibrosis (ICF) and macrophage infiltration by histological methods and for extraction of total RNA and protein. Cont mice had a normal EF of 80±0.6% (n=70), whereas Tg mice had a lower EF (60±2.7%, n=55, p<0.001) coupled with left ventricular dilatation. The distribution of EFs in the Tg mice was large, ranging from normal to below 30%. MCSA and infiltrating macrophages were not different between groups, but ICF increased by 35% in Tg mice. Cre protein levels in heart lysates did not correlate with either age or EF. In contrast to male Tg mice, female Tg mice had no cardiac dysfunction assessed by echocardiography from 12 to 28 weeks of age. To understand gene expression differences between Cont and Tg mice, whole genome gene expression profiling (Illumina BeadChips) on hearts of 30-32 week old male mice was done. Data indicated that 595 genes were overexpressed in the Tg hearts, 156 of which changed more than 2-fold, including genes involved in remodeling, inflammation, and oxidative stress. 512 genes were downregulated in the Cont hearts, 79 of which changed more than 2-fold, including genes involved with calcium handling, K+ channels, and fatty acid transport and metabolism. In conclusion, Cre overexpression and EP4 knock down in cardiac myocytes in aged male but not female Tg mice are in part associated with increased fibrosis, reduced EF and dilated cardiomyopathy; however, Cre protein itself does not seem to be responsible for the cardiomyopathy. The absence of cardiac dysfunction in female mice suggests a sexual dimorphism in the phenotype. Creation of the cardiac-myocyte specific EP4 KO mouse and littermate controls was described in JY Qian et al, Hypertension 2008: 51(pt 2):560-566. Total RNA extracted from left ventricle of control (Cont or WT, n =11) and cardiac-specific EP4 KO (Tg or KO, n=13) male mice (mean age 31 weeks).
2010-04-13 | E-GEOD-16909 | biostudies-arrayexpress
Project description:Dysregulation of ER has been linked with increased metabolic and cardiovascular disease risk. Uncovering the impact of ERα deficiency in specific tissues has implications for understanding the role of ERα in normal physiology and disease, the increased disease risk in postmenopausal women, and the design of tissue-specific ERα-based therapies for a range of pathologies including cardiac disease and cancer. Cardiac myocyte-specific ER knockout mice (ERHKO) were generated to assess the role of ERα in the heart. Female ERHKO mice displayed a mild cardiac phenotype, but unexpectedly, the most striking phenotype was obesity in female ERHKO but not male ERHKO mice. We identified mild cardiac dysfunction, metabolic and lipid dysregulation in hearts of female ERHKO mice. We also show that extracellular vesicles (EVs) collected from the perfusate from Langendorff-isolated hearts from female ERHKO mice have a distinct proteome compared to male ERHKO; enriched for functions associated with muscle, metabolic and fatty acid dysregulation.
2023-01-15 | PXD033078 | Pride
Project description:Dysregulation of ERalpha has been linked with increased metabolic and cardiovascular disease risk. Uncovering the impact of ERα deficiency in specific tissues has implications for understanding the role of ERα in normal physiology and disease, the increased disease risk in postmenopausal women, and the design of tissue-specific ERα-based therapies for a range of pathologies including cardiac disease and cancer. Cardiac myocyte-specific ER knockout mice (ERalphaHKO) were generated to assess the role of ERα in the heart. Female ERHKO mice displayed a mild cardiac phenotype, but unexpectedly, the most striking phenotype was obesity in female ERHKO but not male ERHKO mice. We identified mild cardiac dysfunction, metabolic and lipid dysregulation in hearts of female ERHKO mice. We also show that extracellular vesicles (EVs) collected from the perfusate from Langendorff-isolated hearts from female ERHKO mice have a distinct proteome compared to male ERHKO; enriched for functions associated with muscle, metabolic and fatty acid dysregulation.
2023-01-15 | PXD038482 | Pride
Project description:Analysis of the effects of aging on the development of dilated cardiomyopathy by characterizing both changes in ejection fraction (EF) and gene expression profile in 3 groups of male mice: Control (Cont or WT, n=11) and transgenic (Tg or KO) mice with either high EF (KO-H or Tg-H, n=7) or low EF (KO-L or Tg-L, n=6). We previously produced a line of transgenic mice (Tg) on a mixed genetic background where cardiac-specific overexpression of Cre recombinase reduced expression of the EP4 receptor gene. There were no obvious phenotypes in 10-12-week-old male Tg mice. To determine if a cardiac phenotype developed in aged mice, we assessed cardiac structure and function by echocardiography, histology and gene expression in 23-33-week-old male Tg and littermates (Cont). After echocardiography, hearts were removed to assess hypertrophy (MCSA), fibrosis (ICF) and macrophage infiltration by histological methods and for extraction of total RNA and protein. Cont mice had a normal EF of 80±0.6% (n=70), whereas Tg mice had a lower EF (60±2.7%, n=55, p<0.001) coupled with left ventricular dilatation. The distribution of EFs in the Tg mice was large, ranging from normal to below 30%. MCSA and infiltrating macrophages were not different between groups, but ICF increased by 35% in Tg mice. Cre protein levels in heart lysates did not correlate with either age or EF. In contrast to male Tg mice, female Tg mice had no cardiac dysfunction assessed by echocardiography from 12 to 28 weeks of age. To understand gene expression differences between Cont and Tg mice, whole genome gene expression profiling (Illumina BeadChips) on hearts of 30-32 week old male mice was done. Data indicated that 595 genes were overexpressed in the Tg hearts, 156 of which changed more than 2-fold, including genes involved in remodeling, inflammation, and oxidative stress. 512 genes were downregulated in the Cont hearts, 79 of which changed more than 2-fold, including genes involved with calcium handling, K+ channels, and fatty acid transport and metabolism. In conclusion, Cre overexpression and EP4 knock down in cardiac myocytes in aged male but not female Tg mice are in part associated with increased fibrosis, reduced EF and dilated cardiomyopathy; however, Cre protein itself does not seem to be responsible for the cardiomyopathy. The absence of cardiac dysfunction in female mice suggests a sexual dimorphism in the phenotype. Creation of the cardiac-myocyte specific EP4 KO mouse and littermate controls was described in JY Qian et al, Hypertension 2008: 51(pt 2):560-566.
2010-03-31 | GSE16909 | GEO