Project description:Pulmonary artery banding (PAB) can restore left ventricular (LV) function in infants with end-stage LV dilated cardiomyopathy (LV-DCM), yet the underlying mechanisms remain unclear. Given the transient regenerative capacity of the neonatal heart, we investigated whether pressure overload in one ventricle activates adaptive and regenerative responses in the contralateral ventricle. We induced pressure overload in neonatal mice at postnatal day (P) 0-1 using pulmonary artery banding (nPAB) or transverse aortic constriction (nTAC). In both models, ventricular mass and wall thickness increased not only in the targeted ventricle but also in the contralateral ventricle. These changes were accompanied by cardiomyocyte hyperplasia, preserved systolic function, and enhanced angiogenesis without fibrosis. Bulk and single-nucleus RNA sequencing revealed coordinated activation of pro-proliferative and angiogenic gene programs in both ventricles, including expansion of a cycling cardiomyocyte subpopulation characterized by Ccnd2. In contrast, PAB at P7 resulted in maladaptive hypertrophy, fibrosis, loss of cardiomyocyte proliferation, and impaired biventricular function. These findings reveal an early-life window in which ventricular cross-talk enables a regenerative response to localized pressure overload, supporting the mechanistic rationale for clinical PAB in infants with LV-DCM.
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:Driven by clinical evidence of funcional recovery of the left ventricle (LV) in children with left ventricular dilated cardiomyopathy upon increased right ventricular (RV) pressure by pulmonary aretry banding (PAB) and considering the regenerative capacity of the neonatal mammalian heart, we have explored whether pressure overload in one ventricle could trigger regenerative mechanisms in the other ventricle. Using RNAseq, we identified 636 genes, that were upregulated following nPAB in both the LV and the RV compared to Sham controls. 1052 genes were upregulated in the RV alone, 191 in the LV alone. GO terms assicoated with genes that were upregulated in both ventricles include positive regulation of cell proliferation and angiogenesis. The here uploaded sequancing data supports echocardiographic and immunohistological evidence of an adaptive regulation of both the LV and the RV to an increased RV pressure.
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:Proteomics study of the anthracycline-induced cardiotoxicity in in pigs with pre-existing left ventricular (LV) pressure overload. Large White pigs (2-month-old males and females) were used to induce LV pressure overload via supravalvular aortic stenosis (or sham operation). After 4 months, animals were subsequently exposed to low-risk cumulative doses of anthracyclines (doxorubicin, 5 weekly 1 mg/kg intravenous injections) or vehicle. A total of 16 pigs were divided in four groups: (1) healthy controls (no LV overload or anthracyclines), (2) Doxorubicin (Dox, no LV overload but anthracyclines), (3) Banding (LV overload without anthracyclines), and (4) Banding+Doxorubicin (LV overload plus anthracyclines). A high-throughput quantitative proteomic analysis was performed in myocardial tissue.