Lactation Effects on Postnatal Endothelial Function and Vascular Inflammation

Research project

Description

Mothers who do not breastfeed their infants and those who wean early are at increased risk for cardiovascular disease (CVD) compared with mothers who do breastfeed. There is a dose-dependent inverse relationship between the number of months a woman lactates during her lifetime and cardiovascular events that manifest decades later. Identification of biological mechanisms underlying this association is critical to public health because CVD is the #1 cause of death in U.S. women, killing more than the next five causes combined.

One likely mechanism contributing to increased CVD risk in non-lactating mothers is vascular endothelial dysfunction, which is an early causal factor in the pathogenesis of atherogenic and hypertensive disease The transition from pregnancy to early postpartum is characterized by a ‘perfect storm’ of potent contributors to endothelial damage, including increased systemic and local inflammatory mediators, circulating lipids, visceral fat, and insulin resistance, coupled with reduced levels of protective factors (anti-inflammatory cytokines, cortisol, estrogen). Oxytocin (OT) is one of multiple lactation factors that may influence and protect vascular endothelial function during the high pro-inflammatory postpartum period. OT binds to receptors on vascular endothelium promoting local nitric oxide-dependant vasodilatory and anti-inflammatory activity, and binds to receptors on multiple immune cell sub-types to inhibit acute or prolonged inflammation. Lactation may also protect endothelial function by ‘resetting’ maternal metabolism, reducing pregnancy-induced hyperlipidemia, central fat accumulation and insulin resistance contributing to endothelial damage.

Our central hypothesis is that lactation reduces cardiovascular risk through its salutary effects on endothelial function during the critical first year postpartum. Enhanced or unopposed systemic and local endothelial inflammatory mediators injure vascular endothelium, potentiating chronic disease risk. Lactation mitigates this risk by anti-inflammatory effects at the vascular endothelial surface, regulatory effects on immune cell cytokine production, and metabolic effects on lipid, insulin, glucose, and visceral fat levels that enhance endothelial dysfunction. Our hypothesis is based on our preliminary data showing: (1) More favorable inflammatory (CRP, cell adhesion molecule (CAM)), adrenergic28, glucocorticoid, blood pressure and BMI profiles in breast-feeding compared with formula-feeding mothers; (2) inverse relationships between endothelial adhesion molecules and both FMD and plasma oxytocin. The rationale for the proposed research is that determining the mechanisms through which lactation reduces cardiovascular risk will identify new therapeutic targets for reduction of CVD among parous women. We propose to test our central hypothesis using a longitudinal design to quantify the influence of salient lactation characteristics and associated metabolic changes on biomarkers of endothelial function and inflammation in the first year postpartum by pursuing the following three Specific Aims:

1. To determine the effect of lactation on endothelial function, indexed by brachial artery flow-mediated dilation (FMD) assessed at 2, 6 and 12 months postpartum. We hypothesize that greater breast feeding duration and intensity will predict: 1) Greater FMD response at all time points; 2) Greater FMD increase in response to infant-feeding; 3) Smaller reduction in FMD from 2 to 6 to 12 month assessments. Secondary hypothesis: 4) Plasma OT will partially mediate lactation effects on FMD.

2. To quantify the effect of lactation on systemic and vascular inflammation, assessed at in 3rd trimester and at 2, 6 and 12 months postpartum. We hypothesize that greater breast feeding duration and intensity will predict: 1) Lower levels of vasoconstrictive (endothelin-1) and adhesion (e-selectin, s-VCAM) endothelial products, lower systemic pro-inflammatory facto
StatusFinished
Effective start/end date8/9/135/31/17

Funding

  • NIH National Heart, Lung, and Blood Institute (NHLBI)

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Lactation
Blood Vessels
Inflammation
Postpartum Period
Dilatation
Mothers
Oxytocin
Cardiovascular Diseases
Breast Feeding
Anti-Inflammatory Agents
Intra-Abdominal Fat
Vascular Endothelium
Insulin Resistance
Cytokines
Lipids
Pregnancy
Lactates
Selectins
Brachial Artery
Cell Adhesion Molecules