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Clin Sci (Lond). 2019 May 30;133(10):1185-1196. doi: 10.1042/CS20190141. Print 2019 May 31.

Postnatal inflammation following intrauterine inflammation exacerbates the development of atherosclerosis in ApoE-/- mice.

Author information

1
Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
2
Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia.
3
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Australia.
4
Fakultas Kedokteran, Universitas Indonesia, Indonesia.
5
Department of Paediatrics, University of Melbourne, Parkville, Australia.
6
Department of Paediatrics, Monash University, Clayton, Australia.
7
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Australia tim.moss@monash.edu.
8
Department of Obstetrics and Gynaecology, Monash University, Clayton, Australia.

Abstract

Atherosclerosis is a chronic inflammatory disease that has its origins in early life. Postnatal inflammation exacerbates atherosclerosis, but the possible effect of intrauterine inflammation is largely unexplored. Exposure to inflammation in utero is common, especially in infants born preterm, who have increased cardiovascular risk in adulthood. We hypothesised that exposure to inflammation before birth would accelerate the development of atherosclerosis, with the most severe atherosclerosis following exposure to both pre- and postnatal inflammation. Here we studied the effect of prenatal and postnatal inflammation on the development of atherosclerosis by combining established techniques for modelling histological chorioamnionitis and atherosclerosis using apolipoprotein E (ApoE) knockout mice. A single intra-amniotic (IA) injection of lipopolysaccharide (LPS) caused intrauterine inflammation, and increased atherosclerosis at 13 weeks of postnatal age. In mice exposed to postnatal LPS, chorioamnionitis modulated subsequent responses; atherosclerotic lesion size, number and severity were greatest for mice exposed to both intrauterine and postnatal inflammation, with a concomitant decrease in collagen content and increased inflammation of the atherosclerotic plaque. In conclusion, pre- and postnatal inflammation have additive and deleterious effects on the development of atherosclerosis in ApoE knockout mice. The findings are particularly relevant to preterm human infants, whose gestations are frequently complicated by chorioamnionitis and who are particularly susceptible to repeated postnatal infections. Human and mechanistic studies are warranted to guide preventative strategies.

KEYWORDS:

Chorioamnionitis; Pediatrics; cardiovascular disease; inflammation; pregnancy

PMID:
31088858
DOI:
10.1042/CS20190141

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