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

You-Lin Tain1,2,3, Chien-Ning Hsu4,5

  • 1Division of Pediatric Nephrology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.

International Journal of Molecular Sciences
|March 28, 2024
PubMed

Insights

Prenatal exposure to renin-angiotensin system (RAS) dysregulation can program offspring for cardiovascular-kidney-metabolic (CKM) syndrome. Targeting the RAS may offer a strategy to prevent CKM traits and improve long-term health outcomes.

Area of Science:

  • Reproductive biology
  • Developmental origins of health and disease
  • Cardiovascular and metabolic research

Background:

  • Cardiovascular-kidney-metabolic (CKM) syndrome links metabolic, kidney, and cardiovascular disorders.
  • Prenatal factors are increasingly recognized as contributors to CKM syndrome development.
  • The renin-angiotensin system (RAS) is vital for maternal-fetal health and organ homeostasis.

Purpose of the Study:

  • To review preclinical evidence on RAS dysregulation during pregnancy/lactation and its impact on offspring CKM traits.
  • To elucidate the mechanisms by which RAS influences fetal programming and CKM development.
  • To explore RAS-targeted interventions for preventing early-life CKM syndrome.

Main Methods:

  • Systematic review of preclinical studies on RAS, pregnancy, lactation, and offspring CKM characteristics.
  • Analysis of molecular and physiological mechanisms linking maternal RAS to fetal programming.
  • Literature synthesis on interventions targeting the RAS for CKM trait prevention.

Main Results:

  • Dysregulation of the RAS during critical developmental periods can lead to CKM syndrome characteristics in offspring.
  • The RAS exerts multi-organ effects, influencing fetal programming and establishing CKM traits.
  • Preclinical data supports the RAS as a key mediator in the early-life origins of CKM syndrome.

Conclusions:

  • The RAS plays a significant role in the prenatal programming of CKM syndrome.
  • Targeting the RAS presents a potential strategy for early intervention and prevention of CKM traits.
  • Further research is needed to translate these findings into clinical applications for cardiovascular-kidney-metabolic health.

Keywords:
angiotensin-converting enzymecardiovascular diseasechronic kidney diseasedevelopmental origins of health and disease (DOHaD)hypertensionmetabolic syndromeobesityrenin–angiotensin system

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