Participating mothers were aged 34

Participating mothers were aged 34.03.9 years (no difference between groups). quartile ( 75th percentile) was larger in mothers of NGA-infants (43%) vs. those of SGA-infants (0%, p?=?0.032). Conclusions IgM anti-PC levels are low at birth, which suggests that these antibodies do not play a housekeeping role in immune function during fetal life/development, but arise SKF 82958 predominately on exposure to external antigens after birth. Furthermore, low maternal IgM anti-PC levels may play a role in placental insufficiency, contributing to ZPK poor fetal growth and a small-for-date baby. This preliminary observation may have implications for the future risk of atherosclerosis/cardiovascular disease development in pregnant women and their offspring. Introduction Atherosclerosis, the major cause of cardiovascular disease (CVD), is usually a chronic inflammatory condition characterized by the presence of activated immune qualified cells, such as T-cells and monocytes/macrophages, in atherosclerotic plaques [1]. Phospholipids are highly diversified molecular species ubiquitously expressed in cellular membranes, circulating lipoproteins such as low-density lipoproteins (LDL), and certain pathogens. Phosphorylcholine (PC) has been long recognized as the dominant oxidation-related phospholipid neo-epitope, and is an integral part of the pro-inflammatory phospholipid moiety on oxidized LDL (OxLDL). Interestingly, PC is also present in certain microbial pathogens, thus being a dual danger and pathogen-associated molecular pattern (DAMP/PAMP). Several impartial studies have consistently linked low IgM anti-PC levels to the development of adult atherosclerosis and CVD [2]. Recently, we reported that low IgM anti-PC levels independently predict death and co-morbidity in acute coronary syndrome [3]. The CVD-protective mechanisms of anti-PC have been shown in mice to include anti-inflammatory [4] and anti-atheroslerotic properties [5], as well as perhaps inhibition of OxLDL uptake by macrophages [6], [7] and inhibition of cell-death [8]. Finally, anti-PC antibodies have long been known to be anti-infectious [9]. Based on animal data, IgM anti-PC SKF 82958 antibodies are postulated to be a a part of innate natural antibody pool. They are generated constitutively, without antigenic stimulation, and are non-redundant for efficient clearance of apoptotic debris/cells. Infants given birth to low birth weight, especially those given birth SKF 82958 to small for gestational age (SGA), are at increased life-long risk of developing CVD [10], [11]. Endothelial dysfunction C a key early marker of accelerated atherosclerosis C has been demonstrated in subjects given birth to small, and persists throughout childhood into adult life. Therefore, endothelial dysfunction that begins could be a contributing factor to accelerated vascular ageing [12]C[14]. Studies of animals and monozygous twins indicate that early-onset endothelial dysfunction may result from adverse environmental circumstances before birth e.g. malnutrition, especially late in pregnancy. [15] However, the exact cause of l endothelial SKF 82958 dysfunction in infants given birth to small at term is usually unknown. In this study, we hypothesized that low levels of IgM antibodies against phosphorylcholine during pregnancy could contribute to early-onset endothelial dysfunction, hence play a potential role in mechanisms underlying the increased CVD risk observed in people given birth to small. Subjects and Methods Ethics Statement The study was approved by the Ethics Committee at Karolinska Instututet, Stockholm, Sweden and conformed with the principles of the Helsinki Declaration. Written, informed consent was obtained from all mothers. Participants were 23 mother-infant pairs; 16 mothers delivered a normal birth weight for gestational age infant (NGA; birth weight 3652[504] g) and 7 delivered a small for gestational age infant (SGA; birth weight: 2715[255] g, i.e., more than 2SD below the Swedish mean for normal fetal growth). The mothers were aged 34.0[3.9] years, with no difference between groups. Fourteen neonates were males and seven were girls. All (primi- and multiparous) mothers were healthy, non-smokers, who were not on any special diet and took no medications. Those with manifest (blood pressure; BP 140/90 mm Hg) or borderline hypertension (diastolic BP 85 mm Hg) before pregnancy, insulin-dependent diabetes mellitus, or with indicators of glucose intolerance during pregnancy, were excluded. Gestational age (GA) was determined by.