Project description:In order to better understand sex-related differences of heart failure with preserved ejection fraction (HFpEF), male and female kittens underwent aortic contriction surgery (banding) or sham surgery (normal). Slow progressive pressure overload was then compared between male and female kittens, analyzing structural and functional phenotypes. Transcriptional differences between male and female kittens were investigated via single nuclear RNA sequencing (snRNA-seq) within left ventricle tissue.
Project description:Objectives: Diseased animal models play a crucial role in understanding of the mechanisms and identifying therapeutic targets of human diseases. Left ventricular pressure overload (LVPO) is common in children with various types of cardiovascular diseases, such as aortic valve stenosis and hypertension. However, the current neonatal rat model of LVPO is limited in transverse aortic constriction (TAC) model, characterized by the fixed LVPO and rapid pathological progress of left ventricle, which are not in consistency with the progressive LVPO and relative slow pathological progress of left ventricle in the above pediatric cardiovascular diseases. The purpose of this study is to establish a neonatal rat model of progressive LVPO.
Project description:The goal of this study was to determine developmental differences in gene expression between left and right ventricle, and to assess the differential effect of altered hemodynamic loading on left and right ventricle. Chick ventricles from different developmental stages were isolated for assessment of normal developmental profiles. Conotruncal banding or partial ligation of the left atrial appendage was performed in ovo at embryonic day 4 and ventricles were isolated at embryonic day 5 (banding) or 8 (ligation) for assessment of altered loading effects.
Project description:Hearts(left ventricles) were harvested from control wildtype and ISG15 knockout mice and wildtype and ISG15 knockout mice 4 weeks after pressure overload induced by transverse aortic constriction. Nano LC-MS/MS analysis was performedon left ventricle tissue following protein extraction, trypsin digestion, peptide desalting, anti K-e-GG enrichment.
Project description:The goal of this study was to determine developmental differences in gene expression between left and right ventricle, and to assess the differential effect of altered hemodynamic loading on left and right ventricle. Chick ventricles from different developmental stages were isolated for assessment of normal developmental profiles. Conotruncal banding or partial ligation of the left atrial appendage was performed in ovo at embryonic day 4 and ventricles were isolated at embryonic day 5 (banding) or 8 (ligation) for assessment of altered loading effects. Normal heart and ventricle tissues were collected from chicks at embryonic day 4, 5, 6, 8, or 10 (Hamurger-Hamilton stages 29, 34, and 36). Conotruncal banding (CTB) or left atrial ligation (LCL) was performed for experimental groups in ovo at embryonic day 4 and tissues isolated at embryonic day 5 (CTB) or day 8 (LAL). For each sample type, tissues were carefully dissected, collected and stored in RNAlater, and then pooled for RNA isolation. Each sample contained 6 to 12 separate biological specimens. A single pooled RNA sample was generated for each normal and experimental condition. Following preparation of labeled samples for hybridization, samples were split and hybridized in duplicate to separate microarrays (i.e., technical replicates).
Project description:To investigate the changes in T-UCR (transcribed ultraconserved regions) transcription during aortic banding-induced cardiac hypertrophy, we performed lncRNA microarray analysis on the hearts of mice subjected to sham or aortic banding surgery.
Project description:Heart failure (HF) is the ultimate outcome of most cardiovascular disorders with high prevalence and poor prognosis. The transverse aortic constriction (TAC) method is currently the most widely utilized approach for investigating HF induced by left ventricle pressure overload. We explore potential genes with significant changes in HF through single-cell sequencing.
Project description:We have previously found that overexpression of CHF1/Hey2 in the myocardium prevents the development of phenylephrine-induced hypertrophy. To determine the role of CHF1/Hey2 in pressure overload hypertrophy, we performed ascending aortic banding on wild type and transgenic mice overexpressing CHF1/Hey2 in the myocardium. We found that both wild type and transgenic mice developed increased ventricular weight to body weight ratios one week after aortic banding. Wild type mice also developed decreased fractional shortening after one week when compared to preoperative echocardiograms and sham operated controls. Transgenic mice, in comparison, demonstrated preserved fractional shortening. Histological examination of explanted heart tissue demonstrated extensive fibrosis in wild type hearts, but minimal fibrosis in transgenic hearts. TUNEL staining demonstrated increased apoptosis in the wild type hearts but not in the transgenic hearts. Exposure of cultured neonatal myocytes from wild type and transgenic animals to hydrogen peroxide, a potent inducer of apoptosis, demonstrated increased apoptosis in the wild type cells. Gene Set Analysis of microarray data from wild type and transgenic hearts one week after banding revealed suppression and activation of multiple pathways involving apoptosis, cell signaling and biosynthesis. These findings demonstrate that CHF1/Hey2 promotes physiological over pathological hypertrophy in pressure overload through suppression of apoptosis and global regulation of multiple transcriptional pathways. Experiment Overall Design: Ascending aortic banding on four wild type and four transgenic mice were compared
Project description:Aortic banding is an excellent model system to evaluate the process of development of left ventricular hypertrophy in response to hemodynamic stress. The Affymetrix GeneChip MgU74Av1 was used to analyze expression profiles of mice at different time points after surgical intervention for pressure-overload induced hypertrophy. More information about this model may be obtained at http://cardiogenomics.med.harvard.edu/groups/proj1/pages/band_home.html
Project description:Aortic valve regurgitation (AR) imposes a severe volume overload to the left ventricle (LV) which results in dilation, eccentric hypertrophy and eventually loss of function. Little is known about the impact of AR on LV gene expression. We therefore conducted a gene expression profiling study in the LV of male Wistar rats with chronic (9 months) and severe AR. Five male Wistar rats had one or two aortic valve leaflets punctured with a catheter under echocardiographic guidance in order to induce severe regurgitation (>65% of blood regurgitating during diastole from the aorta to the left ventricle). Five additional rats were sham-operated. The animals were sacrificed 9 months after the procedure and their left ventricle collected for RNA extraction and microarray analysis.
