Project description:Hypertension is a condition with major cardiovascular and renal complications, affecting nearly a billion patients worldwide. Few validated gene targets are available for pharmacological intervention, so there is a need to identify new biological pathways regulating blood pressure and containing novel targets for treatment. The genetically hypertensive “blood pressure high” (BPH), normotensive “blood pressure normal” (BPN), and hypotensive "blood pressure low" (BPL) inbred mouse strains are an ideal system to study differences in gene expression patterns that may represent such biological pathways. We profiled gene expression in liver, heart, kidney, and aorta from BPH, BPN, and BPL mice and determined which biological processes are enriched in observed organ-specific gene signatures. As a result, we identified multiple biological pathways linked to blood pressure phenotype that could serve as a source of candidate genes causal for hypertension. In order to distinguish causal genes from responsive genes in the kidney gene signature we integrated phenotype associated genes into Genetic Bayesian networks, identifying several novel candidate genes causal for hypertension. The integration of data from gene expression profiling and genetics networks is a valuable approach to identify novel potential targets for the pharmacological treatment of hypertension.
Project description:Therefore, we extended our investigation into OSA patients with long-term continuous positive airway pressure (CPAP) treatment, hypertension, or excessive daytime sleepiness (EDS) by analyzing whole-genome gene expression profiles of PBMC in three comparisons: (1) treatment-naïve moderate to very severe OSA patients versus subjects with primary snoring; (2) moderate to very severe OSA patients with hypertension or EDS versus those without hypertension or EDS, respectively; (3) treatment-naïve very severe OSA patients versus those receiving at least one year of adequate CPAP treatment. We analyzed whole-genome gene expression profiles of peripheral blood mononuclear cells from 48 patients with sleep-disordered breathing stratified into four groups: primary snoring (PS), moderate to severe OSA (MSO), very severe OSA (VSO), and very severe OSA patients with long-term continuous positive airway pressure (CPAP) treatment (VSOC).
Project description:Ligand-mediated activation of the nuclear hormone receptor PPAR gamma lowers blood pressure and improves glucose tolerance in humans. Two naturally occurring mutations (P467L, V290M) in the ligand binding domain of PPAR gamma have been described in humans that lead to severe insulin resistance and hypertension. Experimental evidence suggests that these mutant versions of PPAR gamma act in a dominant negative fashion. To better understand the molecular mechanisms underlying PPAR gamma action in the vasculature, we determined the gene expression patterns in mouse aorta in response to activation or interference with the PPAR gamma signaling pathway. Keywords: time course, dose response
Project description:Ligand-mediated activation of the nuclear hormone receptor PPAR gamma lowers blood pressure and improves glucose tolerance in humans. Two naturally occurring mutations (P467L, V290M) in the ligand binding domain of PPAR gamma have been described in humans that lead to severe insulin resistance and hypertension. Experimental evidence suggests that these mutant versions of PPAR gamma act in a dominant negative fashion. To better understand the molecular mechanisms underlying PPAR gamma action in the vasculature, we determined the global gene expression profile in primary aortic endothelial cells in response to endothelial cell specific expression of a dominant negative isoform of PPAR gamma (V290M).
Project description:Long non-coding RNAs (LncRNAs) in hypertensives and their mechanisms in regulating blood pressure still remain unexplored. The aim of present study is to construct the profiles of LncRNAs in blood of patients with essential hypertension and healthy controls. Methods and results, LncRNA microarray identified up-regulated, anddown-regulated LncRNAs, in hypertensives compared to their healthy controls. Among them, one vascular smooth muscle (VSM)-specific LncRNA AK096656 (LncVSM) was quantitated in plasma of patients with hypertension and their healthy controls using the real-time qRT-PCR. LncVSM shows specific expression in human arterial vascular smooth muscle cells (HASMCs) and promote its proliferation and migration. Expression profiles and Ingenuity Pathway Analysis (IPA) revealed that LncVSM activated Renin-Angiotensin Signaling (RAS). the overexpression of LncVSM would result hypertension related complications. LncVSM (AK098656) transfection
Project description:Periodontitis and hypertension often occur as comorbidities. In the face of severe periodontitis patients with hypertension, periodontists often have to give priority to control the patient's blood pressure before surgical treatment, and how to use drugs also brings a lot of inconvenience for clinical treatment. In the stage of periodontal basic treatment, it is a problem that needs to be solved to treat periodontal inflammation and control blood pressure at the same time, so as to achieve “co-treatment of comorbidities”. To this issue, we proposed a controlled-release composite hydrogel approach with dual antibacterial and anti-inflammatory activities as a resolution for pathogen-originated periodontitis. Specifically, chitosan (CS) with inherent antibacterial properties was crosslinked with antimicrobial peptide (AMP) modified polyethylene glycol (PEG) to form the dual antibacterial hydrogel (CS-PA). Subsequently, curcumin nanoparticles (CNP) were encapsulated in the hydrogel to impart anti-inflammatory activities. In the mouse model of periodontitis complicated with hypertension, CS-PA/CNP was applied to gingival sulcus, found that it produced a perfect therapeutic effect on periodontitis and hypertension at the same time. The antibacterial experiments showed that CS-PA/CNP had an excellent inhibitory effect on a variety of periodontal pathogens, demonstrated the potential regulatory ability of the microbiota. In addition, cytological studies revealed the molecular mechanism that CS-PA/CNP enhanced antioxidant capacity of macrophages through the glutathione metabolism pathway, while enhancing their anti-inflammatory capacity. In conclusion, CS-PA/CNP has demonstrated its superior therapeutic effect and potential clinical translational value in the treatment of periodontitis and hypertension, which also serves as a drug delivery platform to provide combinatorial therapeutic options for periodontitis with complicated pathogenesis.
Project description:Long non-coding RNAs (LncRNAs) in hypertensives and their mechanisms in regulating blood pressure still remain unexplored. The aim of present study is to construct the profiles of LncRNAs in blood of patients with essential hypertension and healthy controls. Methods and results, LncRNA microarray identified up-regulated, anddown-regulated LncRNAs, in hypertensives compared to their healthy controls. Among them, one vascular smooth muscle (VSM)-specific LncRNA AK096656 (LncVSM) was quantitated in plasma of patients with hypertension and their healthy controls using the real-time qRT-PCR. LncVSM shows specific expression in human arterial vascular smooth muscle cells (HASMCs) and promote its proliferation and migration. Expression profiles and Ingenuity Pathway Analysis (IPA) revealed that LncVSM activated Renin-Angiotensin Signaling (RAS). the overexpression of LncVSM would result hypertension related complications.
Project description:This study aimed to analyze changes in gut microbiota composition in mice after transplantation of fecal microbiota (FMT, N = 6) from the feces of NSCLC patients by analyzing fecal content using 16S rRNA sequencing, 10 days after transplantation. Specific-pathogen-free (SPF) mice were used for each experiments (N=4) as controls.
Project description:Pharmacological activation of the transcription factor PPAR gamma lowers blood pressure and improves glucose tolerance in humans. In contrast, naturally occurring mutations (e.g., P467L, V290M) in the ligand binding domain of PPAR gamma in humans leads to severe insulin resistance and early-onset hypertension. Experimental evidence, including whole genome expression profiling, suggests that these mutant versions of PPAR gamma act in a dominant negative manner. Because PPAR gamma is expressed in a variety of cell types and tissues, we generated a transgenic mouse model (SP467L) specifically targeting dominant negative PPAR gamma to the vascular smooth muscle cells in order to determine the action of PPAR gamma in the blood vessel independent of its systemic metabolic actions. In the data set provided herein, we examined the gene expression profile in thoracic aorta from SP467L mice and their control littermates using the Affymetrix mouse exon 1.0 ST array.