Transcriptome Profiling of Heart Ageing Reveals Distinct Pathological Gene Network
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE200741 | GEO | 2025/01/29
REPOSITORIES: GEO
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2025-01-23 | GSE283273 | GEO
Project description:Cardiovascular diseases (CVDs) remain the primary cause of global mortality. Nutritional interventions hold promise to reduce CVD risks in an increasingly aging population. However, few nutritional interventions are proven to support heart health and act mostly on blood lipid homeostasis rather than at cardiac cell level. Here, we show that mitochondrial quality and dysfunction are a common hallmark in human cardiomyocytes upon heart aging and in chronic conditions. Preclinically, the post-biotic and mitophagy activator, Urolithin A (UA), reduced both systolic and diastolic cardiac dysfunction in models of natural aging and heart failure. At a cellular level, this was associated with a recovery of mitochondrial ultrastructural defects and mitophagy. In humans, UA supplementation for 4 months in healthy older adults significantly reduced plasma ceramides clinically validated to predict CVD risks. These findings extend and translate UA’s benefits to heart health, making UA a promising nutritional intervention to support cardiovascular function as we age.
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Project description:Cardiac hypertrophy can lead to heart failure, and is induced either by physiological stimuli eg postnatal development, chronic exrcise training or pathological stimuli eg pressure or volume overload. This data set looks at microRNA profiles in mouse models to examine whether phosphoinositide 3-kinase (p110 alpha isoform) activity is critical for the maintenance of cardiac function and long term survival in a seeting of heart failure (myocardial infarction). The significance and expected outcome are to recognise genes involved in models of heart failure and attempt to examine underlying regulator pathways involved in possible cardica maintenance in the PI3K mouse model. The matching mRNA gene expression profile (GSE7487) is examined to look for mRNA and microRNA interactions. miRNA expression correlates directly with cardiac function. PI3K regulon ameliorates cardiac stress. Keywords: microRNA profiling, regulatory pathway discovery, genotype comparison Ntg (non-transgenics), dnPI3K (cardiac-specific transgenic model with reduced PI3K activity) and caPI3K (transgenic mice with increased PI3K activity) mice at 3-4 months of age were used. Mice were then subjected to myocardial infarction (occlusion of the left anterior descending aorta) and sham (open heart surgery) for 8 weeks. Left ventricles were harvested. The resulting 6 experimental models were profiled accordingly. The assignment of the mouse models is as follows: caPI3K Sham, Ntg Sham, dnPI3K Sham, caPI3K MI (myocardial infarction), Ntg MI and dnPI3K MI with n = 4 in each group.
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