Programming of Cardiovascular Dysfunction by Postnatal Overfeeding in Rodents

Abstract

Nutritional environment in the perinatal period has a great influence on health and diseases in adulthood. In rodents, litter size reduction reproduces the effects of postnatal overnutrition in infants and reveals that postnatal overfeeding (PNOF) not only permanently increases body weight but also affects the cardiovascular function in the short- and long-term. In addition to increased adiposity, the metabolic status of PNOF rodents is altered, with increased plasma insulin and leptin levels, associated with resistance to these hormones, changed profiles and levels of circulating lipids. PNOF animals present elevated arterial blood pressure with altered vascular responsiveness to vasoactive substances. The hearts of overfed rodents exhibit hypertrophy and elevated collagen content. PNOF also induces a disturbance of cardiac mitochondrial respiration and produces an imbalance between oxidants and antioxidants. A modification of the expression of crucial genes and epigenetic alterations is reported in hearts of PNOF animals. In vivo, a decreased ventricular contractile function is observed during adulthood in PNOF hearts. All these alterations ultimately lead to an increased sensitivity to cardiac pathologic challenges such as ischemia-reperfusion injury. Nevertheless, caloric restriction and physical exercise were shown to improve PNOF-induced cardiac dysfunction and metabolic abnormalities, drawing a path to the potential therapeutic correction of early nutritional programming.

Keywords: arteries; cardiovascular dysfunction; heart; ischemia; perinatal programming; postnatal overfeeding; rodents.

Figure 1

Cardiac and vascular consequences of neonatal programming by postnatal overfeeding (PNOF) in rodents. PNOF can be induced by litter size reduction, a situation that increases milk consumption during the 24 days after birth and leads to early and long-lasting obesity. Additionally, the expression of several genes is modified in many organs, leading to structural and metabolic alterations. Cardiovascular consequences appear later in life, including altered vasoreactivity and increased arterial blood pressure, ventricular remodelling, cardiac oxidative stress and inflammation, and impaired cardiac contractility and architecture. Altogether, these modifications are responsible for an increased sensitivity to ischemia-reperfusion injury and cardiovascular dysfunction in adulthood.