Gender differences in the cytokines and chemokines gene expression profiles within the medulla oblongata of SHRs
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ABSTRACT: Medulla oblongata is a region of the brain containing multiple blood pressure regulation centers, including the nucleus of the solitary tract (NTS), a pivotal region for regulating the set-point of arterial pressure. Our previous findings suggest that the NTS of male pre-hypertensive rats and spontaneously hypertensive rats (SHRs) exhibits abnormal inflammatory condition compared with that of normotensive Wistar-Kyoto (WKY) rats. Females of SHRs exhibit a lower blood pressure than their male counterpart but the molecular mechanism is not well described. To unveil the gender differences in the central regulation of blood pressure, we investigated the gene expression profile of cytokines and chemokines in the medulla oblongata of female SHRs compared to that of their male counterparts.
Project description:Arterial pressure (AP) is lower in pre-menopausal women than in men of similar age. Pre-menopausal women exhibit a lower sympathetic outflow and a greater baroreceptor reflex, however molecular mechanisms for the gender differences of AP regulation are still not well understood. Since the nucleus tractus solitarius (NTS), a pivotal region of the medulla oblongata for regulating the set-point of AP, is strongly associated with the AP level, we hypothesized that a different neuronal functions at the level of NTS between men and women could contribute to the gender difference in cardiovascular homeostasis. Since females Spontaneous Hypertensive Rats (SHRs) clearly exhibit lower AP levels than their male counterparts at similar age, we investigated whether the NTS of SHRs exhibit gender differences in gene expression by using microarray technique.
Project description:Arterial pressure (AP) is lower in pre-menopausal women than in men of similar age. Pre-menopausal women exhibit a lower sympathetic outflow and a greater baroreceptor reflex, however molecular mechanisms for the gender differences of AP regulation are still not well understood. Since the hypothalmus is strongly functionnaly connected to the nucleus tractus solitarius (NTS), a pivotal region of the medulla oblongata for regulating the set-point of AP, we hypothesized that a different neuronal functions at the level of hypothalamus between men and women could contribute to the gender difference in cardiovascular homeostasis. Since females Spontaneous Hypertensive Rats (SHRs) clearly exhibit lower AP levels than their male counterparts at similar age, we investigated whether the hypothalamus of SHRs exhibit gender differences in gene expression by using microarray technique.
Project description:Arterial pressure (AP) is lower in pre-menopausal women than in men of similar age. Pre-menopausal women exhibit a lower sympathetic outflow and a greater baroreceptor reflex, however molecular mechanisms for the gender differences of AP regulation are still not well understood. Since the nucleus tractus solitarius (NTS), a pivotal region of the medulla oblongata for regulating the set-point of AP is strongly associated with the AP level, we hypothesized that a different neuronal functions at the level of the NTS between men and women could contribute to the gender difference in cardiovascular homeostasis. Females Spontaneous Hypertensive Rats (SHRs) clearly exhibit lower AP levels than their male counterparts at similar age and their NTS is characterized by a specific gene expression profile. This gender dependence of AP level is less marked in the normotensive strain, Wistar Kyoto rats (WKY). In this study, we investigated the gender-dependent gene expression profile of the NTS of WKY by using microarray technique.
Project description:Arterial pressure (AP) is lower in pre-menopausal women than in men of similar age. Pre-menopausal women exhibit a lower sympathetic outflow and a greater baroreceptor reflex, however molecular mechanisms for the gender differences of AP regulation are still not well understood. Since the hypothalmus is strongly functionnaly connected to the nucleus tractus solitarius (NTS), a pivotal region of the medulla oblongata for regulating the set-point of AP, we hypothesized that a different neuronal functions at the level of hypothalamus between men and women could contribute to the gender difference in cardiovascular homeostasis. Females Spontaneous Hypertensive Rats (SHRs) clearly exhibit lower AP levels than their male counterparts at similar age and their hypothalamus is characterized by a specific gene expression profile. This gender dependence of AP level is less marked in the normotensive strain, Wistar Kyoto rats (WKY). In this study, we investigated the gender-dependent gene expression profile of the hypothalamus of WKY rats by using microarray technique.
Project description:Our previous findings suggest that the nucleus of the solitary tract (NTS), a pivotal region for regulating the set-point of arterial pressure, exhibits abnormal inflammation in pre-hypertensive and spontaneously hypertensive rats (SHRs) together with elevated anti-apoptotic and low apoptotic factor levels compared with that of normotensive Wistar–Kyoto (WKY) rats. Whether this chronic condition affects neuronal growth and plasticity in the NTS remains unknown. To unveil the characteristics of the neurodevelopmental environment in the NTS of hypertensive rats, we investigated the gene expression profile of neurotrophins and their receptors in SHRs compared to that of normotensive rat WKY.
Project description:Our previous findings suggest that the nucleus of the solitary tract (NTS), a pivotal region for regulating the set-point of arterial pressure, exhibits abnormal inflammation in pre-hypertensive and spontaneously hypertensive rats (SHRs) together with elevated anti-apoptotic and low apoptotic factor levels compared with that of normotensive Wistar–Kyoto (WKY) rats. Whether this chronic condition affects neuronal growth and plasticity in the NTS remains unknown. To unveil the characteristics of the neurodevelopmental environment in the NTS of hypertensive rats, we investigated the gene expression profile of neurotrophins and their receptors in SHRs compared to that of normotensive rat WKY. The NTS was dissected from the brain of 6 SHRs and 6 WKY rats and the total RNA was extracted. In both groups of rats (SHRs & WKY rats, n = 6 each), a total of 2 ug mRNA extracts from each NTS were pooled together, treated with RNase-free DNAse I (Invitrogen Life technologies) to remove any genomic contamination, and further purified using the RNeasy mini kit (Qiagen) according to the manufacturer’s instructions. Reverse transcription was subsequently performed on 1 ug total RNA using SuperArray’s RT2 First Strand Kit (SABiosciences); the resulting cDNA was submitted for real-time quantitative PCR reactions on RT2 ProfilerTM PCR array plates using Superarray RT2 SYBR Green qPCR Master Mix (SAbiosciences) and iCycler iQ thermal cycler (Bio-rad), following the manufacturer’s instructions. The experiment was performed in duplicate in each group.
Project description:We used spontaneously hypertensive rats (SHRs) as an animal model of hypertensive heart disease and treated them with allisartan orally. We continuously monitored the rats' blood pressure levels, measured their body and heart weights, and evaluated their cardiac structure and function using echocardiography. We performed proteome analysis using the tandem mass tag (TMT) technology.
Project description:Abstract Background: Long-term hypertension can lead to hypertensive heart disease, which ultimately progresses to heart failure. As an angiotensin receptor blocker (ARB) antihypertensive drug, allisartan can control blood pressure and improve cardiac remodeling and cardiac dysfunction caused by hypertension. The objective of this study is to investigate the protective effects of Allisartan on the heart of spontaneously hypertensive rats (SHRs) and the underlying mechanisms. Methods: We used spontaneously hypertensive rats (SHRs) as an animal model of hypertensive heart disease and treated them with allisartan orally at a dose of 25 mg/(Kg·day). We continuously monitored the rats' blood pressure levels, measured their body and heart weights, and evaluated their cardiac structure and function using echocardiography. WGA staining and Masson trichrome staining were employed to assess the morphology of the myocardial tissue. We performed transcriptome and proteome analysis using the Solexa/Illumina sequencing platform and tandem mass tag (TMT) technology, respectively. We used immunofluorescence co-localization to analyze Nrf2 nuclear translocation, and TUNEL to detect the level of cell apoptosis. The protein and mRNA levels were determined by Western blotting and qRT-PCR, respectively. Results: Allisartan lowered blood pressure, attenuated cardiac remodeling, and improved cardiac function. Allisartan alleviated cardiomyocyte hypertrophy and cardiac fibrosis. Allisartan significantly affected the pentose phosphate pathway, fatty acid elongation, valine, leucine and isoleucine degradation, glutathione metabolism, and amino sugar and nucleotide sugar metabolism pathways in the hearts of SHRs, and upregulated the expression level of GSTM2. Allisartan activated the PI3K-AKT-Nrf2 signaling pathway and inhibited cardiomyocyte apoptosis. Conclusions: Our study determined that allisartan effectively controls blood pressure in SHRs and improves cardiac remodeling and cardiac dysfunction. Allisartan upregulates the expression level of GSTM2 in the hearts of SHRs and significantly affects glutathione metabolism shown by transcriptomics and proteomics analysis. The cardioprotective effect of allisartan may be mediated through activation of the PI3K-AKT-Nrf2 signaling pathway, upregulation of GSTM2 expression, and reduction of SHRs cardiomyocyte apoptosis.
Project description:Hypertension is a multifactor disease that possibly involves alterations in gene expression in hypertensive relative to normotensive subjects that are largely unknown. In this study we used high-density oligoarrays to compare gene expression profiles in cultured neurons and glia from pons and medulla oblongata of newborn spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats, a widely documented animal model of hypertension. We found 358 genes differentially expressed between SHR and WKY brainstem cells that preferentially map to 24 metabolic/signaling pathways. Some of the pathways and regulated genes identified herein are obviously related to blood pressure regulation; however there are several genes differentially expressed in SHR not yet associated to hypertension or participating in blood pressure regulation. These constitute a rich resource for the identification and characterization of novel genes involved in hypertension development, or associated to phenotypical differences observed in SHR relative to WKI. In conclusion, this study describes for the first time the gene profiling pattern of brainstem cells from SHR and WKY rats, which opens up new possibilities and strategies of investigation and possible therapeutics to hypertension, as well as for the understanding of the brain contribution in this pathology. Keywords: Gene expression profiling of cultured cells from brainstem of spontaneously hypertensive and normotensive Wistar Kyoto rats
Project description:Left ventricular gene expression profiles from 12-, 16- and 20-months old spontaneously hypertensive rats (SHRs) were compared with left ventricular profiles seen in age-matched Wistar-Kyoto (WKY) rats [control rats] by screening Affymetrix U34A arrays (there are 4 samples in each timepoint except 3 samples of 20-months old WKYs).