Project description:Analysis of kidneys from 12 week BPH/2J hypertensive and age matched normotensive BPN/3J controls - males and females. The results provide insights into the genes that are involved in hypertension in both males and females, as well as highlight mechanisms that underlye sex differences in hypertension. We show that female data can be used to refine candidate genes and pathways, as well as highlight potential mechanisms to explain the differences in prevalence and severity of disease between the sexes. Male and female kidneys from 12 week old hypertensive (BPH/2J) and normotensive (BPN/3J) mice were collected for RNA extraction and hybridization on Affymetrix microarrays. We used data obtained from male and female kidneys to identify common genes that are involved in the development of hypertension in males and females
Project description:Analysis of kidneys from 12 week BPH/2J hypertensive and age matched normotensive BPN/3J controls - males and females. The results provide insights into the genes that are involved in hypertension in both males and females, as well as highlight mechanisms that underlye sex differences in hypertension. We show that female data can be used to refine candidate genes and pathways, as well as highlight potential mechanisms to explain the differences in prevalence and severity of disease between the sexes.
Project description:Identification of hypothalamic genes whose expression differs between high blood pressure (BPH/2J) and normal blood pressure (BPN/3J) Schlager mouse strains at age 6 weeks (young) and 26 weeks (mature) using Affymetrix GeneChip® Mouse Gene 1.0 ST Arrays. The whole hypothalamus was removed from young (6-week-old) and adult (26-week-old) BPH/2J hypertensive mice and age-matched normotensive BPN/2J mice (n=6/group) at peak of 24 h blood pressure. No pooling was performed. After extraction of RNA, cRNA was prepared and arrays performed using Affymetrix GeneChip® Mouse Gene 1.0 ST Arrays at the Ramaciotti Gene Function Analysis facility, University of New South Wales in Sydney, Australia.
Project description:Aims: Hypertension poses a significant challenge to vasculature homeostasis and stands as the most common cardiovascular disease in the world. Its effects are especially profound on vasculature-lining endothelial cells that are directly exposed to the effects of excess pressure. Here, we characterize the in vivo transcriptomic response of cardiac endothelial cells to hypertension using the spontaneous hypertension mouse model BPH/2J. Methods and results: Verification of defective endothelial function in the BPH/2J hypertensive mouse strain was followed by acute isolation of cardiac endothelial cells and transcriptional profiling using RNA sequencing. Gene profiles from normotensive BPN/3J mice were compared to hypertensive animals. We observed over 3000 transcriptional differences between groups including pathways consistent with the cardiac fibrosis found in hypertensive animals. Importantly, many of the fibrosis-linked genes also differ between juvenile pre-hypertensive and adult hypertensive BPH/2J mice, suggesting that these transcriptional differences are hypertension-related. We also show that blood pressure normalization with amlodipine resulted in a subset of genes reversing their expression pattern, supporting the hypertension-dependency of altered gene expression. Yet, other transcripts were recalcitrant to therapeutic intervention illuminating the possibility that hypertension may irreversibly alter some endothelial transcriptional patterns. Conclusions: Hypertension has a profound effect on both function and transcription of endothelial cells, the latter of which was only partially restored with normalization of blood pressure. This study represents one of the first to quantify how endothelial cells are reprogrammed at the molecular level in cardiovascular pathology and advances our understanding of the transcriptional events associated with endothelial dysfunction.
Project description:Identification of hypothalamic genes whose expression differs between active (peak of blood pressure) and inactive periods in the high blood pressure (BPH/2J) Schlager mouse, adjusted by their age- and activity-matched normal blood pressure (BPN/3J) controls using Affymetrix GeneChip® Mouse Gene 1.0 ST Arrays. The whole hypothalamus was removed from BPH/2J and age-matched BPN/2J (n=3/group, 19 week old, ‘trough’ blood pressure) in the inactive period, when the blood pressure levels of the BPH/2J and BPN/3J models are similar. Hypothalamus of BPH/2J and age-matched BPN/2J (n=6/group, 26 week old, ‘peak’ blood pressure) were collected on the same way at the peak of the circadian variation, when there blood pressure difference between the strains was maximal. No pooling was performed. After extraction of RNA, cRNA was prepared and arrays performed using Affymetrix GeneChip® Mouse Gene 1.0 ST Arrays performed at the Ramaciotti Gene Function Analysis facility, University of New South Wales in Sydney, Australia.
Project description:Identification of hypothalamic genes whose expression differs between high blood pressure (BPH/2J) and normal blood pressure (BPN/3J) Schlager mouse strains at age 6 weeks (young) and 26 weeks (mature) using Affymetrix GeneChip® Mouse Gene 1.0 ST Arrays.
Project description:Identification of hypothalamic genes whose expression differs between active (peak of blood pressure) and inactive periods in the high blood pressure (BPH/2J) Schlager mouse, adjusted by their age- and activity-matched normal blood pressure (BPN/3J) controls using Affymetrix GeneChip® Mouse Gene 1.0 ST Arrays.
Project description:The microbiome plays a significant role in gut brain communication and is linked to several animal and human diseases. Hypertension is characterized by gut dysbiosis, and this study aimed to determine how the gut microbiome differed between male and female normotensive and hypertensive rodents. WKY is a genetic control for spontaneous hypertensive rats or SHR which is well documented to have elevated blood pressure at approximately 8 to 10 weeks. We compared the microbiome of normotensive and hypertensive rodents using a meta-genomics approach.
Project description:We examined gene expression profiles in the rat kidneys using genome-wide microarray technology, and determined gene expression profiles in 3 rat strains: normotensive WKY, spontaneously hypertensive rats (SHR), and stroke-prone SHR (SHRSP). To identify candidate genes involved in the genesis of hypertension in the SHR strains, we compared the gene expression levels at 3 and 6 weeks of age, isolated 407 genes showing a more than 4-fold increase or a less than 1/4-fold decrease. The rat kidneys derived from normotensive WKY, spontaneously hypertensive rats (SHR), and stroke-prone SHR (SHRSP) were examined. Each strain was run in triplicate.