Mechanisms underlying developmental programming of elevated blood pressure and vascular dysfunction: evidence from human studies and experimental animal models

Clin Sci (Lond). 2008 Jan;114(1):1-17. doi: 10.1042/CS20070113.

Abstract

Cardiovascular-related diseases are the leading cause of death in the world in both men and women. In addition to the environmental and genetic factors, early life conditions are now also considered important contributing elements to these pathologies. The concept of 'fetal' or 'developmental' origins of adult diseases has received increased recognition over the last decade, yet the mechanism by which altered perinatal environment can lead to dysfunction mostly apparent in the adult are incompletely understood. This review will focus on the mechanisms and pathways that epidemiological studies and experimental models have revealed underlying the adult cardiovascular phenotype dictated by the perinatal experience, as well as the probable key causal or triggering elements. Programmed elevated blood pressure in the adult human or animal is characterized by vascular dysfunction and microvascular rarefaction. Developmental mechanisms that have been more extensively studied include glucocorticoid exposure, the role of the kidneys and the renin-angiotensin system. Other pathophysiological pathways have been explored, such as the role of the brain and the sympathetic nervous system, oxidative stress and epigenetic changes. As with many complex diseases, a unifying hypothesis linking the perinatal environment to elevated blood pressure and vascular dysfunction in later life cannot be presumed, and a better understanding of those mechanisms is critical before clinical trials of preventive or 'deprogramming' measures can be designed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Animals
  • Cardiovascular Diseases / embryology
  • Cardiovascular Diseases / etiology*
  • Disease Models, Animal
  • Female
  • Fetal Development
  • Humans
  • Hypertension / embryology
  • Hypertension / etiology
  • Infant Nutritional Physiological Phenomena
  • Infant, Newborn
  • Oxidative Stress
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Vascular Diseases / embryology
  • Vascular Diseases / etiology