Unraveling the complexities of cardiorenal syndrome: epigenetic and post-translational modification perspectives

Cardiorenal syndrome (CRS) is a complex condition where heart and kidney dysfunctions interact, leading to high morbidity and mortality. It presents significant challenges in cardiovascular and renal medicine due to its prevalence and severe outcomes. Traditional models focus on hemodynamic issues, renin–angiotensin–aldosterone system activation, oxidative stress, and inflammation but fall short in explaining CRS's chronic and varied nature. Recent research in epigenomics and proteomics highlights the importance of epigenetic regulation and post-translational modifications (PTMs) in CRS development. Epigenetics provides stable, long-term gene regulation related to diseases without changing the DNA sequence, mainly through DNA methylation, histone modification, and non-coding RNA regulation. In contrast, PTMs quickly alter protein function and signaling via ubiquitination, phosphorylation, acetylation, and newer processes like lactoylation and carbamylation. Both play key roles in CRS by affecting inflammation, fibrosis, and mitochondrial dysfunction, and are linked through a complex regulatory network. This review details the mechanisms and interactions between epigenetics and PTMs in CRS, emphasizing their potential as biomarkers and therapeutic targets, and discusses research limitations and future directions to advance understanding.