Katariina Öörni (Finland)Wihuri Research Institute Atherosclerosis Research Laboratory
Author Of 5 Presentations
Introduction (ID 1523)
Introduction (ID 1584)
Live Q&A (ID 1386)
O053 - Lp(a) induces inflammasome activation in human macrophages (ID 474)
Background and Aims
Elevated Lp(a) serum levels are associated with increased risk for atherosclerotic coronary artery disease and stroke. Here, we analyzed the effect of plasma Lp(a) levels on caspase-1 and the pro-inflammatory cytokines it processes. We further directly compare the molecular composition of Lp(a) and LDL isolated from the same donors as well as their pro-atherogenic and pro-inflammatory potential.
Human plasmas with varying Lp(a) levels and isolated Lp(a) and LDL were incubated with THP-1 macrophages for three hours and caspase-1 activation and the release of pro-inflammatory cytokines IL-1β, IL-1α, and IL-18 was measured. Molecular composition of Lp(a) and LDL isolated from the same donors was determined by lipidomics and proteomics approaches.
Plasma Lp(a) levels ranging from 1.7 to 165.3 mg/dL correlated significantly with caspase-1 activity (r = 0.496), IL-18 (r = 0.496), and IL-1α (r = 0.447) in macrophages. IL-1β secretion correlated significantly with plasma triglycerides, and not with Lp(a) levels.
Lipidomics comparison of LDL and Lp(a) indicated that Lp(a) was significantly depleted of poly-unsaturated fatty acids in all lipid classes. Proteomics analyses revealed that Lp(a) is enriched in inflammation-associated proteins. Lp(a) from induced robust and dose-dependent caspase-1 activation and release of IL-1β and IL-18 compared to a mild induction upon incubation with LDL from the same donors.
Our data show that plasma Lp(a) levels directly correlate with inflammasome activation in macrophages, isolated Lp(a) induces stronger dose-dependent caspase-1 activation than LDL, and LDL and Lp(a) have clear structural differences additionally to apo(a).
O062 - Children with familial hypercholesterolemia display changes in LDL and HDL function: a cross-sectional study (ID 1406)
Background and Aims
The functional status of lipoprotein particles contributes to atherogenesis. The tendency of plasma LDL particles to aggregate and the ability of HDL particles to induce and mediate reverse cholesterol transport associate with high and low risk for cardiovascular disease in adult patients, respectively. However, it is unknown whether children with familial hypercholesterolemia (FH) display lipoprotein function alterations.
We hypothesized that FH children had disrupted lipoprotein function.
We analyzed LDL aggregation susceptibility and HDL-apoA-I exchange to apoA-I ratio (HAE/apoA-I ratio), and activity of four proteins that regulate lipoprotein metabolism (CETP, LCAT, PLTP and PON1) in plasma samples derived from children with FH (n = 47) and from healthy children (n = 56). Potential biological mechanisms behind any variation in lipoprotein functionalities were explored using an NMR-based metabolomics profiling approach.
LDL aggregation was higher and HAE/apoA-I ratio was lower in FH children than in healthy children. LDL aggregation associated positively with LDL-C and negatively with triglycerides, and HAE/apoA-I ratio associated negatively with LDL-C. Generally, the metabolomic profile for LDL aggregation was a mirror image of that for HAE/apoA-I ratio.
FH children displayed increased atherogenicity of LDL and disrupted HDL function. These newly observed functional alterations in LDL and HDL may help explain the risk for atherosclerotic cardiovascular disease in FH children.