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Urolithin A Provides Cardioprotection and Mitochondrial Quality Enhancement Preclinically and Improves Cardiovascular Health Biomarkers in Humans

ABSTRACT: 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.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE283003 | GEO | 2025/01/23

REPOSITORIES: GEO

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Urolithin A Provides Cardioprotection and Mitochondrial Quality Enhancement Preclinically and Improves Cardiovascular Health Biomarkers in Humans [mouse_cardiac_aging]

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The impact of long term cigarette smoke, but not Tobacco Heating System 2.2 exposure on the genes involved in cardiac muscle structure and function in Apoe-/- mouse.

Project description:Cigarette smoking is a major risk factor for the development and progression of diseases such as cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD). Modified risk tobacco products (MRTP) are designed to reduce smoking-related health risks. Suitable animal models are important for understanding smoke-induced pathogenesis. Over an 8-month period, hallmarks of CVD were investigated in ApoE?/? mice exposed to conventional cigarette smoke (CS) or to an aerosol from a candidate RRP, the tobacco heating system (THS2.2). In addition to chronic exposure, cessation or switching to THS2.2 after 2 months of CS were investigated.ﾠ The aim of this study was to evaluate the transcriptomics response of mouse heart tissue after exposure to 3R4F and a potential reduced risk tobacco product, Tobacco Heating System 2.2 (THS2.2). The transcriptomic analysis of heart tissue, showed that cigarette smoke strongly impacted the differential expression of genes at long term of smoke exposure at 6 and 8 month, whereas the new THS2.2 not burning product donﾒt present any significant impact on the genes expression on cardiovascular tissue. In a similar manner, cessation and switching exposure donﾒt present any significant regulation of genes. Functional analysis of differentially expressed genes shown that 3R4F exposure strongly regulate the cytoskeleton organization and contraction and shown a down regulation of actin, actinin alpha 4, the main component of sarcomere structure. These preliminary results suggest that the conventional smoking product may favours the development of cardiomyopathy via a direct impact of the cardiomyocytes structure and that the inflammatory process could also be affected by the smoke exposure and could be responsible for the non-adaptive response of heart to a stress.

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