Project description:In hypertension, abnormal regulation of microcirculation and endothelial dysfunction enhances vulnerability to hypertensive brain damage. In addition to lowering blood pressure, blockade of Angiotensin II AT1 receptors protects against stroke and stress in different animal models and this treatment may be of therapeutic advantage. We studied gene expression using Affymetrix Rat Genome U34A arrays from brain microvessels of spontaneously hypertensive rats (SHR) and their normotensive Wistar Kyoto controls (WKY) rats treated with an AT1 antagonist (candesartan, 0.3 mg/kg/day) or vehicle via osmotic minipumps for 4 weeks. Experiment Overall Design: brain microvessels from hypertensive and normotensive rats treated with candesartan and vehicle were analyzed
Project description:In hypertension, abnormal regulation of microcirculation and endothelial dysfunction enhances vulnerability to hypertensive brain damage. In addition to lowering blood pressure, blockade of Angiotensin II AT1 receptors protects against stroke and stress in different animal models and this treatment may be of therapeutic advantage. We studied gene expression using Affymetrix Rat Genome U34A arrays from brain microvessels of spontaneously hypertensive rats (SHR) and their normotensive Wistar Kyoto controls (WKY) rats treated with an AT1 antagonist (candesartan, 0.3 mg/kg/day) or vehicle via osmotic minipumps for 4 weeks. Keywords: other
Project description:Hypertension is a risk factor for brain damage. Here we tested whether protection of the brain depends on the type of antihypertensive medication. We compared normotensive rats to untreated hypertensive rats and hypertensive rats treated with either amlodipine or atenolol. After one year treatment we sampled CSF for broad screening of brain damage markers using proteomic analysis. The hypothesis is that the drug amlodipine (a vasodilator) is more protective for the brain than atenolol (a beta-blocker that mainly acts on the heart) and this would show up in CSF protein profiles. Both systolic and diastolic blood pressure were increased in hypertensive rats in comparison to their normotensive controls, and both medications lowered blood pressure as compared to untreated SHR rats. The analysis of the CSF proteome revealed that hypertension resulted in alterations to processes associated with the development of the central nervous system, as well as with inflammation and blood coagulation. The latter included proteins such as YKL-40, KNG1, DAG1, and members of the Serpin family. Amlodipine treatment resulted in changes to proteins involved in gas transport (including CA2, HBB, and HBA1), whereas atenolol treatment had no significant effect on any biological pathway. A comparison of the two antihypertensive treatments revealed alterations in pathways associated with cell adhesion, central nervous system development, and vascular development.
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: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:Knee osteoarthritis (KOA), as a degenerative multifactorial disease, affects the quality of life and mental health of patients, and also brings a huge socioeconomic burden. Treating synovitis have shown promise as anti-inflammatory therapeutics in mitigating OA symptoms and disease progression. Here, by analysing synovial single-cell sequencing (scRNA-seq) data from KOA, we found that synovial fibroblasts (FLS) in OA synovium showed a distinct pro-inflammatory phenotype. We collected synovial tissue from patients with clinical OA as well as from healthy donors, and histological examination was consistent with findings in scRNA-seq. Inspired by recent cross-tissue fibroblast lineage studies, we identified by sequencing that healthy FLS in synovial tissues share transcriptome-level similarities with dermal fibroblasts (DFb). Subsequently, we revealed the local as well as systemic distribution of intra-articular injected DFbs by constructing/extracting two types of rat fibroblasts (luciferase DFbs as well as GFP DFbs). The results demonstrate that DFbs can be locally retained in the synovium for up to three weeks following targeted engrafting on it. And intra-articular injection does not result in DFbs migration to vital organs or the occurrence of histological changes in these organs. A rat model of KOA was constructed by anterior cruciate ligament transection (ACLT) in order to study the therapeutic effect of DFbs on KOA. After injection, the rats showed improvement in painful gait. In addition, histological as well as imaging results showed reduced synovitis and improvement in articular cartilage. Finally we verified the protective effect of DFbs on cytokine-stimulated chondrocytes in a co-culture system.
Project description:Left ventricle gene expression was analyzed in three models of hypertension in order to clarify the molecular mechanisms associated with left ventricular hypertrophy. Transgenic heterozygous TGR(mRen2)27 rats, overexpressing the mouse renin gene, and their littermate negative controls, spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY), and Lyon hypertensive rats (LH) and their normotensive controls (LL) were included in the study.