RASopathies and Cardiac Complications: Insights into Mechanisms, Diagnosis, and Innovative Treatments.

RAS proteins are critical in cellular signal transduction, influencing cell proliferation, differentiation, and survival. While extensively studied for their role in cancer, RAS gene mutations also contribute significantly to cardiovascular diseases, such as hypertrophic cardiomyopathy, pulmonary valve stenosis, and atrial septal defects. Despite their similar primary structures, RAS proteins exhibit distinct functions in cardiac biology: H-RAS regulates cardiomyocyte size, K-RAS governs proliferation, and N-RAS, less associated with cardiac defects, is understudied in cardiac cells. Congenital RAS mutations, collectively known as RASopathies, include syndromes, like Noonan syndrome and cardio-facio-cutaneous syndrome, which often lead to severe cardiac complications, including heart failure. Genetic testing and imaging advances have improved the diagnosis and management of these conditions. Recent research has shown promise with MEK inhibitors and other targeted therapies, offering potential improvements in managing RAS-related cardiac conditions. This review explores the role of the RAS subfamily in heart disease, highlighting key concepts and potential therapeutic targets. PubMed database was searched using keywords, such as RASopathies, RAS gene mutations, cardiac hypertrophy, cardiovascular disease, RAS/MAPK pathway, congenital heart disease, and more. Relevant literature up to June 2024 was examined and summarized, consisting of data from various clinical trials, metaanalyses, retrospective/prospective cohort studies, and current guidelines.