Human primary hepatocyte transcriptome analysis upon treatment with rosuvastatin and implication on cardiac Atrial Natriuretic Peptides level

Abstract

The relationship between rosuvastatin and cardiac Atrial Natriuretic Peptides (ANP) levels has been explored in previous studies, while, the exact mechanisms underlying the modulation of ANP levels by rosuvastatin are not fully understood. Therefore, the aim of this study is to investigate the likely mechanism associated with changes in ANP levels following treatment with rosuvastatin. The study used 42 male Wistar rats, weighing 120-140 g, divided into six groups, to investigate the impact of Multidrug resistance 1 (MDR1) mutations and high-fat diet on serum lipid profiles. Rats were acclimatized for 2 weeks, given different diets, and treated with Rosuvastatin. The experiment lasted for 12 weeks, and serum NT-pro ANP was measured using ELISA. Microarray datasets from the GEO database were analyzed for differentially expressed genes using R software and enriched for gene ontology and KEGG pathways. There was a significant increase in ANP levels in the high-fat diet group treated with rosuvastatin in the evening compared to all other groups (P < 0.05). Similar trend was observed in the normal diet group treated with rosuvastatin either in the morning or evening (p-value < 0.05). After 48-hour treatment with rosuvastatin, the gene MVK displayed upregulation with a log²(fold change) of 1.291, CYB5B exhibited upregulation with a log²(fold change) of 2.477, FDFT1 showed upregulation with a log²(fold change) of 2.292, and SFN exhibited upregulation with a log²(fold change) of 3.8. While these findings provide insights into the potential mechanisms underlying the enhancement of cardiac ANP secretion, further research is necessary to confirm the functional relevance of these genes and the clinical significance of their effects on ANP levels in humans.