Project description:We used transverse aortic constraction pressure overload hypertrophy mouse hearts as a model of cardiovascular disease to study the genetic changes between TAC and SHAM (normal) mouse hearts and over 1 circadian cycle (24h). This is one approach to identify diurnal genetic biomarkers of cardiovascular disease. The micorarray approach allowed to see the gene expression in all genes in cardiovascular disease and sham hearts. There are 36 samples of cardiovascular disease (TAC) and normal SHAM hearts. For TAC: There were 3 mice sacrificed at each time point as biological replicates, for 6 timepoints over 24 hrs. For SHAM: There were 3 mice sacrificed at each time point as biological replicates, for 6 timepoints over 24 hrs.
Project description:We used transverse aortic constraction pressure overload hypertrophy mouse hearts as a model of cardiovascular disease to study the genetic changes between TAC and SHAM (normal) mouse hearts and over 1 circadian cycle (24h). This is one approach to identify diurnal genetic biomarkers of cardiovascular disease. The micorarray approach allowed to see the gene expression in all genes in cardiovascular disease and sham hearts.
Project description:Environmental stressors present in the modern world can have a fundamental effect on the physiology and health of humans. Exposure to stressors like air pollution, heat and traffic noise has been linked to a pronounced increase in non-communicable diseases. Specifically, aircraft noise has been identified as a risk factor for cardiovascular and metabolic diseases, such as arteriosclerosis, heart failure, stroke and diabetes. Noise stress leads to neuronal activation with subsequent stress hormone release that ultimately leads to activation of the renin-angiotensin-aldosterone system, increasing inflammation and oxidative stress, with dramatic effects on the cardiovascular system. However, despite the epidemiological evidence of a link between noise stress and metabolic dysfunction, the consequences of exposure at the molecular, metabolic level of the cardiovascular system are largely unknown. Here we use a murine model system of aircraft noise exposure to show that noise stress profoundly alters heart metabolism. Within days of exposing animals to aircraft noise the heart has a reduced potential for utilising fatty-acid beta-oxidation, the tricarboxylic acid cycle, and the electron transport chain for generating ATP. This is compensated by shifting energy production towards glycolysis. Intriguingly, the metabolic shift is reminiscent of what is observed in failing and ischaemic hearts. Our results demonstrate that within a relatively short exposure time, the cardiovascular system undergoes a fundamental metabolic shift that bears the hallmarks of cardiovascular disease. Overall, aircraft noise induces rapid, detrimental metabolic shifts in the heart, resembling patterns seen in cardiovascular diseases. These findings underscore the urgent need to comprehend molecular consequences of environmental stressors, paving the way for targeted interventions aiming mitigating health risks associated with chronic noise exposure in our modern, noisy environments.
Project description:Smoking is one of the major modifiable risk factors in the development and progression of chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD). Modified-risk tobacco products (MRTP) are being developed to provide substitute products for smokers who are unable or unwilling to quit, to lessen the smoking-related health risks. In this study, the ApoE-/- mouse model was used to investigate the impact of cigarette smoke (CS) from the reference cigarette 3R4F, or aerosol from two potential MRTPs based on the heat-not-burn principle, carbon-heated tobacco product 1.2 (CHTP 1.2) and tobacco heating system 2.2 (THS 2.2), on the cardiovascular and respiratory system over a 6-month period. In addition to chronic exposure, cessation or switching to CHTP1.2 after 3 months of CS exposure was assessed. A systems toxicology approach combining physiology, histology and molecular measurements (transcriptomics and proteomics) was used to evaluate the impact of MRTP aerosols in comparison to CS. The current data represent the lung transcriptomics analysis. Note that the animal identifier (CAN) can be used for sample matching across different sample types and data modalities.
Project description:Smoking is one of the major modifiable risk factors in the development and progression of chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD). Modified-risk tobacco products (MRTP) are being developed to provide substitute products for smokers who are unable or unwilling to quit, to lessen the smoking-related health risks. In this study, the ApoE-/- mouse model was used to investigate the impact of cigarette smoke (CS) from the reference cigarette 3R4F, or aerosol from two potential MRTPs based on the heat-not-burn principle, carbon-heated tobacco product 1.2 (CHTP 1.2) and tobacco heating system 2.2 (THS 2.2), on the cardiovascular and respiratory system over a 6-month period. In addition to chronic exposure, cessation or switching to CHTP1.2 after 3 months of CS exposure was assessed. A systems toxicology approach combining physiology, histology and molecular measurements (transcriptomics and proteomics) was used to evaluate the impact of MRTP aerosols in comparison to CS. The current data represent the lung transcriptomics analysis. Note that the animal identifier (CAN) can be used for sample matching across different sample types and data modalities.
Project description:We sought to characterize cellular composition across the cardiovascular system of the healthy Wistar rat, an important model in preclinical cardiovascular research. We performed snRNA-seq in 78 samples in 10 distinct regions including the four chambers of the heart, ventricular septum, sinoatrial node, atrioventricular node, aorta, pulmonary artery, and pulmonary veins, which produced 505,835 nuclei. We identified 26 distinct cell types and additional subtypes, with different cellular composition across cardiac regions and tissue-specific transcription for each cell type. Several cell subtypes were region-specific, including a subtype of vascular smooth muscle cells enriched in the large vasculature. We observed tissue-enriched cellular communication networks, including heightened Nppa - Npr1/2/3 signaling in the sinoatrial node. The existence of tissue-restricted cell types suggests regional regulation of cardiovascular physiology. Our detailed transcriptional characterization of each cell type offers the potential to identify novel therapeutic targets and improve preclinical models of cardiovascular disease.