The Renin–Angiotensin System and Cardiovascular–Kidney–Metabolic Syndrome: Focus on Early-Life Programming

Abstract

The identification of pathological links among metabolic disorders, kidney ailments, and cardiovascular conditions has given rise to the concept of cardiovascular–kidney–metabolic (CKM) syndrome. Emerging prenatal risk factors seem to increase the likelihood of CKM syndrome across an individual’s lifespan. The renin–angiotensin system (RAS) plays a crucial role in maternal–fetal health and maintaining homeostasis in cardiovascular, metabolic, and kidney functions. This review consolidates current preclinical evidence detailing how dysregulation of the RAS during pregnancy and lactation leads to CKM characteristics in offspring, elucidating the underlying mechanisms. The multi-organ effects of RAS, influencing fetal programming and triggering CKM traits in offspring, suggest it as a promising reprogramming strategy. Additionally, we present an overview of interventions targeting the RAS to prevent CKM traits. This comprehensive review of the potential role of the RAS in the early-life programming of CKM syndrome aims to expedite the clinical translation process, ultimately enhancing outcomes in cardiovascular–kidney–metabolic health.

The Impact of the Aryl Hydrocarbon Receptor on Antenatal Chemical Exposure-Induced Cardiovascular–Kidney–Metabolic Programming

“…The DOHaD theory establishes a connection between early life programming and various recognized facets of CKM syndrome, including cardiovascular disease (CVD) [6], metabolic disease [12], hypertension [13], CKD [14], and obesity [15]. Several molecular mechanisms linked to CKM programming have been discovered, such as an aberrant renin-angiotensin system (RAS), epigenetic dysregulation, deficient nitric oxide (NO), disturbances in nutrientsensing signals, oxidative stress, and gut microbiota dysbiosis [16][17][18][19][20][21]. Conversely, by targeting these pivotal mechanisms, there is a shift in focus from managing diseases during adulthood to intervening in disease processes before they clinically manifest, known as reprogramming, which holds promising potential as a preventive strategy.…”