The role and mechanisms of methylation modifications in the development and progression of hypertension

Hypertension is a globally prevalent cardiovascular disorder with a multifactorial etiology involving genetic variations, environmental cues, aging and their complex interactions. Despite extensive research, the precise molecular mechanisms by which these factors drive hypertension remain incompletely elucidated. Traditional research has focused on classic pathological pathways, including renin-angiotensin-aldosterone system (RAAS) activation, endothelial dysfunction, oxidative stress, chronic inflammation, and sympathetic nervous system (SNS) overactivation, but emerging epigenetic evidence indicates that aberrant methylation patterns mediate the upstream dysregulation of these pathways. As pivotal regulatory bridges integrating genetic susceptibility and environmental signals, methylation modifications directly influence essential hypertensive processes, including RAAS hyperactivation, SNS overactivity, impaired renal sodium handling, and pathological vascular remodeling. This review comprehensively summarizes current advances in methylation-related mechanisms underlying hypertension pathogenesis, and clarifies how genetic variants, environmental risk factors and aging synergistically induce methylation abnormalities to promote disease progression. By integrating mechanistic insights with translational potential, this work provides a foundation for precision medicine approaches, enabling the development of methylation-based early diagnostic biomarkers, risk stratification strategies, and targeted epigenetic therapies aimed at improving clinical outcomes in hypertension.