Welcome to the EAS 2022 Interactive Program
The congress will officially run on CET time zone (Central European Time, Milano)
Dietary components and patterns as determinants of cardiovascular risk
Exercise and cardiovascular disease in 2022: When,who and how ?
WESTERN-TYPE DIET OVERRULES THE PROTECTIVE EFFECT OF COMMENSAL BACTERIA IN ATHEROGENESIS
Background and Aims
Studies have shown that atherosclerosis is associated with an altered gut microbiota composition (dysbiosis). However, studies have shown contradictory findings and the mechanistic effects are lacking.
To study the role of gut microbiota in atherosclerosis, male and female germ-free (GF) low-density lipoprotein knockout (Ldlr-/-) mice were conventionalized (CONV) with fecal microbiota from sex-matched Ldlr-/- donor mice or remained GF. Mice (n=12/group) were fed a chow or western-type diet (WD) for 12 weeks.
Atherosclerotic plaque size was significantly reduced in chow-fed CONV mice compared to GF mice, with females displaying larger plaque sizes than males (p<0.05). In males, this athero-protective effect was independent of plasma cholesterol and systemic inflammation, whereas plasma cholesterol was reduced in female CONV mice compared to their GF counterparts (p<0.05). In contrast, the athero-protective effect was lost in WD-fed mice as plaque size was similar in CONV and GF mice, independent of gender. To investigate whether the microbiota could explain this atherosclerosis phenotype, we analyzed gut microbiota composition and function. 16S rRNA sequencing revealed a different microbial composition between chow-fed male and female mice, however, a sex difference was not found in WD-fed mice. Moreover, an increase in the Firmicutes:Bacteroidetes ratio was observed in WD-fed mice compared to chow-fed mice, indicative of microbial dysbiosis. Cecal SCFAs and plasma BA were similarly affected by chow and WD in CONV compared to GF mice, excluding an athero-protective role of these metabolites.
WD overrules the protective effect of commensal bacteria in atherogenesis, which is independent of BA- and SCFA metabolism.
EARLY LIFE INFECTION IS ASSOCIATED WITH PROINFLAMMATORY, ATHEROGENIC, AND DIABETOGENIC METABOLOMIC AND LIPIDOMIC PROFILES AT 12 MONTHS OF AGE
Background and Aims
Infection is linked to later cardiometabolic disease, but the mechanisms are poorly understood, particularly in early life when most infection occurs. We investigated the relationship of infectious burden (from birth to 12 months) with NMR metabolomic and LC/MS lipidomic profiles at 12 months of age, and whether inflammation mediated these effects.
Plasma metabolomics and lipidomics were quantified in 12-month plasma from 555 infants in the Barwon Infant Study who had complete data on parent-reported infections in the first year of life. In linear regression models adjusted for confounders, the exposure was total number of infections as a continuous variable, and outcomes were 12-month metabolomic and lipidomic measures. We investigated whether inflammation (glycoprotein acetyls (GlycA) and high-sensitivity C-reactive protein (hsCRP)) mediated effects using structural-equation modeling.
More infections were associated with higher inflammation markers and phenylalanine; and with lower high-density lipoprotein cholesterol, apolipoprotein A1, and docosahexaenoic acid. In lipidomic analysis, more infections were associated with higher phosphatidylethanolamines and lower plasmalogens; and lower ceramide and hexosylceramides species. Higher 12-month GlycA was associated with similar, more pronounced profiles. GlycA mediated a substantial proportion of the associations between infections and metabolomic and lipidomic measures (9.2-39.9%). hsCRP showed little evidence of mediating the relationship between infections and metabolomic or lipidomic measures. differences.
Higher infectious burden in infancy is associated with pro-inflammatory, pro-atherogenic, and diabetogenic metabolomic and lipidomic profiles. Inflammation may partly mediate the metabolic effects of infection. These findings suggest potentially modifiable pathways linking early life infection, inflammation, and cardiometabolic risk.
MICROPLASTIC PARTICLES INDUCE ENDOTHELIAL ACTIVATION
Background and Aims
Although microplastics being omnipresent in our environment and already detected in various organisms, less is known about the effects of microplastics on vascular biology in particular. Here we investigated the effects of carboxylated polystyrene (PS) microplastic particles (1 µm) on murine endothelial and immune cells, which are both crucially involved in vascular inflammation.
Murine monocytic J774A.1 cells and endothelial MyEND cells were stimulated with PS particles (3/6 hrs, n=7-10). mRNA and protein levels were analyzed using real-time PCR and ELISA. Adhesion assays were performed incubating confluent MyEND cells with PS particles and Calcein-AM labelled J774A.1 (static/flow). Adherent J774A.1 were detected by fluorescence microscopy (n=6). C57BL/6J mice were injected with TRITC-conjugated PS i.v. (n=6/group). PS particles were localized in blood and liver using IHC staining.
In J774A.1 cells, PS particles induced Il1-β and Tnf-α expression and TNF-α release. In MyEND cells, PS particles up-regulated Icam-1 and Vcam-1 levels and sVCAM-1 release. PS particles induced adhesion of J774A.1 cells on endothelial monolayers under static as well as under flow conditions. In vivo, PS particles taken up by neutrophiles (Ly6G-positive) in the peripheral blood. PS particles accumulated in the liver, accompanied by a strong up-regulation of the acute phase proteins Saa1, Saa2 and Saa3. Moreover, Aortic tissue from mice injected with PS particles showed enhanced Il-1β and Vcam-1 expression.
PS particles are able to activate the endothelium with subsequent monocyte adhesion, representing a hallmark of vascular inflammation. Thus, microplastics need to be evaluated as a potential novel environmental risk factor for endothelial inflammation.