| 1. |
- Tabassum, R, et al.
(författare)
-
Genetic architecture of human plasma lipidome and its link to cardiovascular disease
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4329-
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD.
|
|
| 2. |
- Ruuth, M., et al.
(författare)
-
Susceptibility of low-density lipoprotein particles to aggregate depends on particle lipidome, ismodifiable, and associates with future cardiovascular deaths
- 2018
-
Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 39:27
-
Tidskriftsartikel (refereegranskat)abstract
- Aims Low-density lipoprotein (LDL) particles cause atherosclerotic cardiovascular disease (ASCVD) through their retention, modification, and accumulation within the arterial intima. High plasma concentrations of LDL drive this disease, but LDL quality may also contribute. Here, we focused on the intrinsic propensity of LDL to aggregate upon modification. We examined whether inter-individual differences in this quality are linked with LDL lipid composition and coronary artery disease (CAD) death, and basic mechanisms for plaque growth and destabilization. Methods and results We developed a novel, reproducible method to assess the susceptibility of LDL particles to aggregate during lipolysis induced ex vivo by human recombinant secretory sphingomyelinase. Among patients with an established CAD, we found that the presence of aggregation-prone LDL was predictive of future cardiovascular deaths, independently of conventional risk factors. Aggregation-prone LDL contained more sphingolipids and less phosphatidylcholines than did aggregation-resistant LDL. Three interventions in animal models to rationally alter LDL composition lowered its susceptibility to aggregate and slowed atherosclerosis. Similar compositional changes induced in humans by PCSK9 inhibition or healthy diet also lowered LDL aggregation susceptibility. Aggregated LDL in vitro activated macrophages and T cells, two key cell types involved in plaque progression and rupture. Conclusion Our results identify the susceptibility of LDL to aggregate as a novel measurable and modifiable factor in the progression of human ASCVD.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- O'Dwyer, J, et al.
(författare)
-
Methanesulfonic acid in a Svalbard ice core as an indicator of ocean climate
- 2000
-
Ingår i: GEOPHYSICAL RESEARCH LETTERS. - 0094-8276. ; 27:8, s. 1159-1162
-
Tidskriftsartikel (refereegranskat)abstract
- Methanesulfonic acid (MSA) is an atmospheric oxidation product of dimethyl sulfide, produced by marine biota. MSA preserved in a Svalbard glacier between 1920 and 1996 is compared with the sea surface temperature (SST) and sea-ice extent of the surrounding ocean over the same period. On decadal timescales high MSA concentrations are found to be associated with warm SST and reduced sea-ice extent. MSA appears to be influenced by climatic changes related to variations in the import of warm Atlantic Water to the Barents Sea. Atlantic Water plays an important role in the Arctic climate system, therefore MSA concentrations may indirectly reflect larger-scale changes in the region and may be useful as a proxy for past climate.
|
|
| 9. |
- Pohjola, V, et al.
(författare)
-
Effect of periodic melting on geochemical and isotopic signals in an ice core from Lomonosovfonna, Svalbard
- 2002
-
Ingår i: J.Geophys.Res.. ; 107:D4, s. ACL 1-14
-
Tidskriftsartikel (refereegranskat)abstract
- In this work we examine the quality of the atmospherically deposited signals in an ice core taken from a periodically melting ice field, Lomonosovfonna on central Spitsbergen, Svalbard. The aim is to investigate how much the atmospheric deposited signals in the stratigraphy of ice pack are changed by periodic melting of the ice. To determine the impact of this melting on the stratigraphy found in the ice core, we use three diagnostics: 1) Association between peak values in the ice chemical and isotopic record and ice facies type; 2) Number of “annual” cycles in these records compared with independently-determined number of years represented in the ice core; 3) Statistical comparison between the isotopic record in the ice core and the isotope records from coastal stations from the same region. We find that during warm summers as much as 50% of the annual accumulation may melt and percolate into the firn, and in a median year this decreases to ca. 25 %. As a consequence of percolation the most mobile acids show upto 50 % higher concentrations in bubble poor ice facies compared with facies that are less affected by melt. Most of the other chemical species are less affected than the strong acids, and the stable water isotopes show little evidence of mobility Annual, or bi-annual cycles are detected in most parameters, and the water isotope record has a comparable statistical distribution to isotopic records from coastal stations. We conclude that ice cores from sites like Lomonosovfonna preserve an useful environmental record despite melt events and percolation, where most parameters displays an annual, or in poor cases a bi-annual atmospheric signal.
|
|
| 10. |
- Pussinen, PJ, et al.
(författare)
-
Periodontitis decreases the antiatherogenic potency of high density lipoprotein.
- 2004
-
Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 45:1, s. 139-147
-
Tidskriftsartikel (refereegranskat)abstract
- Periodontitis, a consequence of persistent bacterial infection and chronic inflammation, has been suggested to predict coronary heart disease (CHD). The aim of this study was to investigate the impact of periodontitis on HDL structure and antiatherogenic function in cholesterol efflux in vitro. HDL was isolated from 30 patients (age 43.6 +/- 6.1 years, mean +/- SD) with periodontitis before and after (3.2 +/- 1.4 months) periodontal treatment. The capacity of HDL for cholesterol efflux from macrophages (RAW 264.7), HDL composition, and key proteins of HDL metabolism were determined. After periodontal treatment, phospholipid transfer protein (PLTP) activity was 6.2% (P<0.05) lower, and serum HDL cholesterol concentration, PLTP mass, and cholesteryl ester transfer protein activity were 10.7% (P<0.001), 7.1% (P=0.078), and 19.4% (P<0.001) higher, respectively. The mean HDL2/HDL3 ratio increased from 2.16 +/- 0.87 to 3.56 +/- 0.48 (P<0.05). HDL total phospholipid mass and sphingomyelin-phosphatidylcholine ratio were 7.4% (P<0.05) and 36.8% (P<0.001) higher, respectively. The HDL-mediated cholesterol efflux tended to be higher after periodontal treatment; interestingly, this increase was significant (P<0.05) among patients whose C-reactive protein decreased (53.7% reduction, P=0.015) and who were positive by PCR for Actinobacillus actinomycetemcomitans. These results suggest that periodontitis causes similar, but milder, changes in HDL metabolism than those that occur during the acute-phase response and that periodontitis may diminish the antiatherogenic potency of HDL, thus increasing the risk for CHD.
|
|
