Developmental conditioning of the vasculature

Clough, G. (2015) Developmental conditioning of the vasculature. Comprehensive Physiology, 5, 397-438. (doi:10.1002/cphy.c140037). (PMID:25589274)

Record type: Article

Abstract

There is increasing evidence from epidemiological and experimental animal studies that the early life environment, of which nutrition is a key component, acts through developmental adaptive responses to set the capacity of cardiovascular and metabolic pathways to respond to physiological and pathophysiological challenges in later life. One finding that is consistent to both population studies and animal models is the propensity for such effects to induce endothelial dysfunction throughout the vascular tree, including the microvasculature. Obesity, type 2 diabetes and hypertension are associated with changes in microvascular function affecting multiple tissues and organs. These changes may be detected early, often before the onset of macrovascular disease and the development of end organ damage. Suboptimal maternal nutrition and fetal growth result in reduced microvascular perfusion and functional dilator capacity in the offspring, which together with microvascular rarefaction and remodeling serve to limit capillary recruitment, reduce exchange capacity and increase diffusion distances of metabolic substrates; they also increase local and overall peripheral resistance. This article explores how a developmentally conditioned disadvantageous microvascular phenotype may represent an important and additional risk factor for increased susceptibility to the development of cardio-metabolic disease in adult life and considers the cell signaling pathways associated with microvascular dysfunction that may be “primed” by the maternal environment. As the microvasculature has been shown to be a potential target for early therapeutic and lifestyle intervention, this article also considers evidence for the efficacy of such strategies in humans and in animal models of the developmental origins of health and diseas

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