Project description:Severe forms of hypertension are characterized by high blood pressure combined with end-organ damage. Through the development and refinement of a transgenic rat model of malignant hypertension (MH) incorporating the mouse renin gene, we previously identified a quantitative trait locus (QTL) on chromosome 10, which affects malignant hypertension severity and morbidity. We next generated an inducible MH model where the timing, severity and duration of hypertension was placed under the control of the researcher, allowing development of and recovery from end-organ damage to be investigated. We have now generated novel consomic Lewis (L) and Fischer (F) rat strains with inducible hypertension, and additional strains, which are reciprocally congenic for the refined chromosome 10 QTL – FL (Fischer with a Lewis congenic region and LF (Lewis with a Fischer congenic region). We have captured a modifier of end-organ damage within the QTL and, using a range of bioinformatic, biochemical and molecular biological techniques, have identified Angiotensin converting enzyme (Ace) as the modifier of tissue microvascular injury. This SuperSeries is composed of the SubSeries listed below.
Project description:High blood pressure or Primary Hypertension is associated with target organ damage (TOD) in both adults and youth, where TOD predicts the adverse cardiovscular (CV) events. The mechanisms involved in blood pressure mediated TOD are limitedly understood in onset of TOD. To understand this, first using RNA sequencing, we identified candidate differentially expressed genes in circulating PBMCs of study participants with and without hypertension and elevated left ventrivlar mass index . Next, through miRNA and whole genome bisulphite sequencing of circulating PBMCs we determined the epigenetic regulators of TOD. Also, using LCMS, serum proteomics, the key circulatory protein involved in advancing CV- TOD events was identified. In conclusion, multiomics approach was utilized to define the circulatory regulators involved in BP mediated CV-TOD.
Project description:High blood pressure or Primary Hypertension is associated with target organ damage (TOD) in both adults and youth, where TOD predicts the adverse cardiovscular (CV) events. The mechanisms involved in blood pressure mediated TOD are limitedly understood in onset of TOD. To understand this, first using RNA sequencing, we identified candidate differentially expressed genes in circulating PBMCs of study participants with and without hypertension and elevated left ventrivlar mass index . Next, through miRNA and whole genome bisulphite sequencing of circulating PBMCs we determined the epigenetic regulators of TOD. Also, using LCMS, serum proteomics, the key circulatory protein involved in advancing CV- TOD events was identified. In conclusion, multiomics approach was utilized to define the circulatory regulators involved in BP mediated CV-TOD.
Project description:High blood pressure or Primary Hypertension is associated with target organ damage (TOD) in both adults and youth, where TOD predicts the adverse cardiovscular (CV) events. The mechanisms involved in blood pressure mediated TOD are limitedly understood in onset of TOD. To understand this, first using RNA sequencing, we identified candidate differentially expressed genes in circulating PBMCs of study participants with and without hypertension and elevated left ventrivlar mass index . Next, through miRNA and whole genome bisulphite sequencing of circulating PBMCs we determined the epigenetic regulators of TOD. Also, using LCMS, serum proteomics, the key circulatory protein involved in advancing CV- TOD events was identified. In conclusion, multiomics approach was utilized to define the circulatory regulators involved in BP mediated CV-TOD.
Project description:High blood pressure or Primary Hypertension is associated with target organ damage (TOD) in both adults and youth, where TOD predicts the adverse cardiovscular (CV) events. The mechanisms involved in blood pressure mediated TOD are limitedly understood in onset of TOD. To understand this, first using RNA sequencing, we identified candidate differentially expressed genes in circulating PBMCs of study participants with and without hypertension and elevated left ventrivlar mass index . Next, through miRNA and whole genome bisulphite sequencing of circulating PBMCs we determined the epigenetic regulators of TOD. Also, using LCMS, serum proteomics, the key circulatory protein involved in advancing CV- TOD events was identified. In conclusion, multiomics approach was utilized to define the circulatory regulators involved in BP mediated CV-TOD.
Project description:High blood pressure or Primary Hypertension is associated with target organ damage (TOD) in both adults and youth, where TOD predicts the adverse cardiovscular (CV) events. The mechanisms involved in blood pressure mediated TOD are limitedly understood in onset of TOD. To understand this, first using RNA sequencing, we identified candidate differentially expressed genes in circulating PBMCs of study participants with and without hypertension and elevated left ventrivlar mass index . Next, through miRNA and whole genome bisulphite sequencing of circulating PBMCs we determined the epigenetic regulators of TOD. Also, using LCMS, serum proteomics, the key circulatory protein involved in advancing CV- TOD events was identified. In conclusion, multiomics approach was utilized to define the circulatory regulators involved in BP mediated CV-TOD.
Project description:High blood pressure or Primary Hypertension is associated with target organ damage (TOD) in both adults and youth, where TOD predicts the adverse cardiovscular (CV) events. The mechanisms involved in blood pressure mediated TOD are limitedly understood in onset of TOD. To understand this, first using RNA sequencing, we identified candidate differentially expressed genes in circulating PBMCs of study participants with and without hypertension and elevated left ventrivlar mass index . Next, through miRNA and whole genome bisulphite sequencing of circulating PBMCs we determined the epigenetic regulators of TOD. Also, using LCMS, serum proteomics, the key circulatory protein involved in advancing CV- TOD events was identified. In conclusion, multiomics approach was utilized to define the circulatory regulators involved in BP mediated CV-TOD.