Project description:This study examined the renal gene expression profiles between spontaneously-hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at a pre-hypertensive stage (3 weeks of age) and hypertensive stage (9 weeks of age). In addition, age-related changes in gene expression patterns were examined from 3 to 9 weeks in both WKY and SHR. Five to six individual kidney samples of the same experimental group were pooled together and quadruplicate hybridizations were performed on the NIEHS Rat v2.1, 2.2 and 3.0 arrays. Keywords: other
Project description:This study examined the renal gene expression profiles between spontaneously-hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at a pre-hypertensive stage (3 weeks of age) and hypertensive stage (9 weeks of age). In addition, age-related changes in gene expression patterns were examined from 3 to 9 weeks in both WKY and SHR. Five to six individual kidney samples of the same experimental group were pooled together and quadruplicate hybridizations were performed on the NIEHS Rat v2.1, 2.2 and 3.0 arrays.
Project description:Genome wide DNA methylation profiling of hypertensive, pre-hypertensive, and healthy control samples. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles. Samples included 44 hypertensive samples, 44 pre-hypertensive samples, and 44 healthy controls.
Project description:To determine if there exists a consistent gene signature associated with vascular hypertrophy among different rat hypertensive models: treated and untreated Wistar Kyoto (WKY) rats and treated and untreated Spontaneous Hypertensive Rat (SHR) rats. Keywords: strain comparison, treatment vs control
Project description:We have used Affymetrix microarray-driven gene profiling to comprehensively describe the expression of mRNAs in the nucleus tractus solitarii (NTS) in the adult male spontaneously hypertensive rat (SHR) as compared to its normotensive parental Wistar-Kyoto (WKY) strain. Keywords: Gene expression
Project description:Hypertension remains a poorly understood condition, and the understanding of the sympathetic nervous systems role in this disease remains even more limited. In this study, RNA-sequencing is used to identify transcriptomal differences in the sympathetic stellate ganglia between the 16-week-old normotensive wistar strain and the spontaneously hypertensive rat strain.This dataset should allow for further molecular characterisation of hypertensive changes in a cardiac-innervating sympathetic ganglion.
Project description:Animals. Male Sprague–Dawley rats (Charles River Laboratories, Wilmington, MA) weighing about 250g were used. The study was approved by the Thomas Jefferson University Institutional Animal Care and Use Committee and was conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. The animals were housed in Thomas Jefferson University's animal care facilities. Animals were anesthetized with isoflurane dissolved in O2 (5% induction; 1% maintenance) and one femoral artery and vein were cannulated (PE-50 tubing) via a small medial incision for measurement of arterial pressure and infusion of drugs, respectively. The cannulae were run subcutaneously to an exit incision between the scapulae. The leg wound was sutured and topical anesthetic (lidocaine) was applied to both skin incisions. Following surgery, after one hour of stable and normal resting blood pressure and heart rate, intravenous infusion was initiated of approximately 1 mL saline, as a control, or phenylephrine (200 µg/mL; 1 mL/hr), to induce hypertension. We followed standard methods in the use of phenylephrine (PE) to elevate blood pressure. PE does not cross the blood brain barrier and the elevated blood pressure it produces has been shown to cause molecular effects in the NTS principally via increased baroreceptor afferent drive by both pharmacological and sinoaortic denervation studies. We titered the PE dose to maintain intermediate levels of elevated blood pressure 25 mmHg above resting blood pressure. Keywords: Hypertension, time series
Project description:Using transcriptomic we looked for changes in large-scale gene expression profiling of leukocytes of hypertensive patients with left ventricular remodeling compared to hypertensive patients without left ventricular remodeling and to control and whether these changes reflect metabolic pathway regulation already shown by positron emission tomography. Genes encoding for glycolytic enzymes were found over-expressed in the group of hypertensive patients with left ventricular remodeling. Expression of master genes involved in fatty acids β-oxidation was unchanged.
Project description:We have used Affymetrix microarray-driven gene profiling to comprehensively describe the expression of mRNAs in the nucleus tractus solitarii (NTS) in the adult male spontaneously hypertensive rat (SHR) as compared to its normotensive parental Wistar-Kyoto (WKY) strain. Keywords: Gene expression NTS was dissected from hypertensive (SHR) and normotensive (WKY) strains of rat. For each structure, 10 independent Affymetrix Genechip 230 2.0 experiments were performed (5 SHR, 5 WKY), with each chip representing an independent biological replication (n=5).
Project description:RATIONALE: Hypertension can lead to podocyte damage and subsequent apoptosis, eventually resulting in glomerulosclerosis. Although alleviating podocyte apoptosis has clinical significance for the treatment of hypertensive nephropathy, an effective therapeutic target has not yet been identified. The function of Septin4, a pro-apoptotic protein and an important marker of organ damage, is regulated by post-translational modification (PTM). However, the exact role of Septin4 in regulating podocyte apoptosis and its connection to hypertensive renal damage remains unclear. OBJECTIVE: We investigated the function and underlying mechanism of Septin4 in AngII-induced hypertensive nephropathy to discover a theoretical basis for targeted treatment. METHODS AND RESULTS: Using transgenic Septin4-K174Q mutant mice treated with the antioxidant Tempol, we found that hyperacetylation of the K174 site of Septin4 exacerbates AngII induced hypertensive renal injury resulting from oxidative stress. Proteomics and western blotting assays indicated that Septin4-K174Q activates the cleaved-PARP1-cleaved-Caspase3 pathway. In Septin4-knockdown human renal podocytes, Septin4-K174R, which mimics deacetylation at K174, rescues podocyte apoptosis induced by AngII. We conclude that Septin4, when activated through acetylation of K174 (K174Q), promotes hypertensive renal injury. Immunoprecipitation and mass spectrometry analyses identified SIRT2 as a deacetylase that interacts with the Septin4 GTPase domain and deacetylates Septin4-K174. In Sirt2-deficient mice and SIRT2-knockdown renal podocytes, Septin4-K174 remains hyperacetylated and exacerbates hypertensive renal injury. By contrast, in Rosa26-Sirt2-Flag (SIRT2-TG) mice and SIRT2-knockdown renal podocytes re-expressing wild-type SIRT2, Septin4-K174 is hypoacetylated and mitigates hypertensive renal injury. CONCLUSION: Septin4-K174R, which mimics deacetylation by SIRT2, inhibits the cleaved-PARP1-cleaved-Caspase3 pathway. Septin4-K174R acts as a renal protective factor, mitigating AngII-induced hypertensive renal injury. These findings indicate that Septin4-K174 is a potential therapeutic target for the treatment of hypertensive renal injury.