Skip to main content
Login | Suomeksi | På svenska | In English

Browsing by Subject "LDL"

Sort by: Order: Results:

  • Camelina sativa -öljyn vaikutus ihmisen veren LDL-partikkelien lipidikoostumukseen 
    Fredrikson, Linda (2019)
    The consumption of omega (n-) 3 polyunsaturated fatty acids (PUFA) from fish has been associated with lower rates of cardiovascular diseases with one mechanism being lowering LDL cholesterol levels in blood. When incorporated into LDL particle n-3 PUFAs can modify the lipid composition and reduce atherogenicity of the particle, e.g. by influencing inflammatory processes. The effects of n-3 PUFA of plant origin are less studied. This study investigated the effects of Camelina sativa oil (CSO), a rich source of alpha-linolenic acid (ALA), on lipid species of human LDL including phosphatidylcholines (PC), lysophosphatidylcholines (LPC), sphingomyelin (SM), triacylglycerols (TAG) and cholesterol esters (CE). A total of 38 subjects with a history of impaired fasting glucose, were randomly divided into two groups; CSO (ALA 10 g/day) and the control group (limited fish and ALA intake) for 12 weeks. Blood samples were collected from the subjects at the beginning and at the end of the experiment after 12 weeks. LDL particles were isolated from blood and the lipids were analyzed by mass spectrometry. The CSO affected more the LDL core lipids (TAG and CE) than lipid species of the shell (PC, LPC, SM). CSO is high in ALA and linoleic acid (LA). Thus, the diet reduced mole fractions of lipid species containing saturated acyl chains while acyl chains in the core lipids with ALA, LA and EPA, that is formed in the body from ALA, were increased. Based on the results, having CSO in the diet changed the LDL particle lipid composition in a favorable direction for cardiovascular health.
  • Large-scale Generation and Characterization of LDLRAP1 Variants in Hypercholesterolemia 
    Erten, Nehir Birke (2024)
    Hypercholesterolemia is characterized by elevated levels of low-density lipoprotein (LDL) cholesterol in the bloodstream and contributes substantially to the global burden of atherosclerotic cardiovascular disease (ASCVD). Low-density lipoprotein receptor adaptor protein 1 (LDLRAP1) is an endocytic adaptor protein which assists LDL internalization by promoting LDLR localization in clathrin-coated pits and mutations in LDLRAP1 are associated with autosomal recessive hypercholesterolemia. However, the clinical relevance of many LDLRAP1 variants is yet to be fully determined. The aim of this master’s thesis is to adopt an analysis pipeline for bulk generation and functional characterization of such LDLRAP1 variants. To accomplish this goal, a cell model with impaired LDLR internalization is validated and the activity of LDLRAP1 and LDLRAP1 variants are evaluated within this system. This involves implementing a semi-automated variant generation pipeline to produce LDLRAP1 variants in large-scale, and LDLRAP1 variants are introduced into this cell system. The main finding of this thesis is that impaired LDLRAP1 function results in LDL-LDLR complexes to be retained on plasma membrane. The expression of LDLRAP1-GFP in internalization deficient cells reduced LDL and LDLR accumulation on plasma membrane. These features were evaluated for variant characterization, revealing three variants that may have impaired LDLRAP1 functionality. In conclusion, the findings of this thesis underscore the imperative for large-scale variant generation efforts and highlight the pivotal role of LDLRAP1 functionality in LDL internalization.
  • Mass Spectrometry-Based Lipidomics Indicates that Consumption of Fatty Fish Alters the lipid species Profile of Human LDL 
    Bhalke, Monika (2020)
    Lipoproteins are biochemical carriers of the insoluble lipids. They are complexes combining lipids and proteins for the transport of lipids. Amongst the type of lipoproteins are low-density lipoproteins (LDL) which are prevalent in various diseases such as obesity, diabetes, atherosclerosis, and other cardiovascular diseases (CVD). Omega-3 fatty acids are polyunsaturated fatty acids (PUFA) that are essential components of lipid metabolism and play a significant role in the human diet. Omega-3 PUFAs such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are derived from fish and are necessary for proper cardiovascular functioning. Because the human body is unable to produce enough quantities of some omega-3, diet is an important source for its availability. When a diet is rich in saturated fats, the above-mentioned diseases transpire. This study investigated how consumption of two fish diets, Lean fish and Fatty fish, influence the lipid species of human LDL particles. The lipid species analysed in this study are phospholipids such as phosphatidylcholine (PC), sphingomyelin (SM), and lysophosphatidylcholine (LPC), and cholesteryl esters (CE), and triacylglycerols (TAG). A total of 42 volunteers with a history of impaired fasting glucose had randomly been divided into two groups: fatty fish (4 fish meals/week) and lean fish (4 fish meals/week) for 12 weeks. Blood samples had been collected from the volunteers before and after consumption of the fish meals and LDL particles had been isolated from the blood samples by ultracentrifugation. In this study, the lipids were extracted by Folch method, and the extracted lipids were analysed using Triple quadrupole mass spectrometry. The lipid class profile did not change due to the two fish type diets. However, the consumption of fatty fish diet increased the levels of lipid species of PC, LPC, and CE containing EPA and DHA acyl chains, while decreasing levels of several TAG species. Lean fish induced minor changes in the lipid composition of LDL particles. Based on these results, fatty fish diet alters the plasma LDL lipidome profile with changes induced to both the surface and the core composition of the LDL particles in a positive way regarding cardiovascular health.

Yhteystiedot

HELSINGIN YLIOPISTO