| 1. |
- Correa M., Yubexi Y.
(författare)
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Role of lipoprotein structure and dynamics in disease development : from atherosclerosis to Covid-19
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lipoproteins play a crucial role in lipid metabolism, serving as carriers for lipids such as cholesterol and triglycerides in the bloodstream. Atherosclerosis is a complex cardiovascular disease characterized by the accumulation of cholesterol-rich plaques in arterial walls, leading to narrowed and hardened arteries. Recently, the spike protein from the SARS-CoV-2 virus, responsible for COVID-19, has been the subject of research concerning its potential impact on lipid metabolism and its association with cardiovascular disease. Understanding the interaction between lipoproteins and the spike protein influence on lipid metabolism could have implications for our knowledge of cardiovascular health.In this research, we investigated the ultrastructure of HDL from individuals with different lipid profiles as well as the interaction of mature HDL and model of nascent HDL with model membranes. Understanding these differences will help create novel rHDL particles with superior lipid-removing and CVD-treating properties. Finally, the interaction between the spike protein and HDL in model cell membranes to study potential imbalances in lipid metabolism. To achieve the different objectives, lipid deposition, exchange and removal were followed by techniques such as Neutron reflection and attenuated total reflection Fourier transformation infrared spectroscopy while, the ultrastructure was unravelled by small-angle X-ray scattering.
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| 2. |
- Correa, Yubexi, et al.
(författare)
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High-Density Lipoprotein function is modulated by the SARS-CoV-2 spike protein in a lipid-type dependent manner
- 2023
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier. - 0021-9797 .- 1095-7103. ; 645, s. 627-638
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Tidskriftsartikel (refereegranskat)abstract
- There is a close relationship between the SARS-CoV-2 virus and lipoproteins, in particular high-density lipoprotein (HDL). The severity of the coronavirus disease 2019 (COVID-19) is inversely correlated with HDL plasma levels. It is known that the SARS-CoV-2 spike (S) protein binds the HDL particle, probably depleting it of lipids and altering HDL function. Based on neutron reflectometry (NR) and the ability of HDL to efflux cholesterol from macrophages, we confirm these observations and further identify the preference of the S protein for specific lipids and the consequent effects on HDL function on lipid exchange ability. Moreover, the effect of the S protein on HDL function differs depending on the individuals lipid serum profile. Contrasting trends were observed for individuals presenting low triglycerides/high cholesterol serum levels (LTHC) compared to high triglycerides/high cholesterol (HTHC) or low triglycerides/low cholesterol serum levels (LTLC). Collectively, these results suggest that the S protein interacts with the HDL particle and, depending on the lipid profile of the infected individual, it impairs its function during COVID-19 infection, causing an imbalance in lipid metabolism.
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| 3. |
- Correa, Yubexi, et al.
(författare)
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Lipid exchange of apolipoprotein A-I amyloidogenic variants in reconstituted high-density lipoprotein with artificial membranes
- 2024
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Ingår i: Protein Science. - : John Wiley & Sons. - 0961-8368 .- 1469-896X. ; 33:5
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Tidskriftsartikel (refereegranskat)abstract
- High-density lipoproteins (HDLs) are responsible for removing cholesterol from arterial walls, through a process known as reverse cholesterol transport. The main protein in HDL, apolipoprotein A-I (ApoA-I), is essential to this process, and changes in its sequence significantly alter HDL structure and functions. ApoA-I amyloidogenic variants, associated with a particular hereditary degenerative disease, are particularly effective at facilitating cholesterol removal, thus protecting carriers from cardiovascular disease. Thus, it is conceivable that reconstituted HDL (rHDL) formulations containing ApoA-I proteins with functional/structural features similar to those of amyloidogenic variants hold potential as a promising therapeutic approach. Here we explored the effect of protein cargo and lipid composition on the function of rHDL containing one of the ApoA-I amyloidogenic variants G26R or L174S by Fourier transformed infrared spectroscopy and neutron reflectometry. Moreover, small-angle x-ray scattering uncovered the structural and functional differences between rHDL particles, which could help to comprehend higher cholesterol efflux activity and apparent lower phospholipid (PL) affinity. Our findings indicate distinct trends in lipid exchange (removal vs. deposition) capacities of various rHDL particles, with the rHDL containing the ApoA-I amyloidogenic variants showing a markedly lower ability to remove lipids from artificial membranes compared to the rHDL containing the native protein. This effect strongly depends on the level of PL unsaturation and on the particles' ultrastructure. The study highlights the importance of the protein cargo, along with lipid composition, in shaping rHDL structure, contributing to our understanding of lipid–protein interactions and their behavior.
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| 4. |
- Correa, Yubexi
(författare)
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Receptor-Independent Lipid Exchange of ApoA-I Amyloidogenic Variants in Reconstituted High-Density Lipoprotein
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- High-density lipoproteins (HDLs) are responsible for removing cholesterol from arterial walls, through a process known as reverse cholesterol transport. The main protein in HDL, apolipoprotein A-I (ApoAI), is essential to this process, and changes in its sequence significantly alter HDL structure and functionality. ApoA-I amyloidogenic variants, associated with a hereditary degenerative disease, are particularly effective at facilitating cholesterol removal, thus protecting carriers from cardiovascular disease. Thus, it is conceivable that reconstituted HDL (rHDL) formulations containing ApoA-I proteins with functional/structural features of amyloidogenic variants hold potential as a promising therapeutic approach. In this work, we explored the effect of protein cargo and lipid composition on the function of rHDL containing either the native ApoA-I or the amyloidogenic variants G26R and L174S. Moreover, we uncovered the structural and functional differences between rHDL particles to comprehend structural features that cause a rise in cholesterol efflux activity despite an apparent lower phospholipid (PL)affinity. Our findings indicate distinct trends in lipid exchange (removal versus deposition) capacities of various rHDL particles depending on protein cargo and PL unsaturation. Notably, the choice of lipid cargo influenced rHDL structure, resulting in smaller and more elliptical particles when POPC was used instead of DMPC. The study highlights the importance of the protein cargo, along with lipid composition, in shaping rHDL structure, contributing to our understanding of lipid-protein interactions and their behaviour.
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| 5. |
- Correa, Yubexi, et al.
(författare)
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SARS-CoV-2 spike protein removes lipids from model membranes and interferes with the capacity of high density lipoprotein to exchange lipids
- 2021
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier. - 0021-9797 .- 1095-7103. ; 602, s. 732-739
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Tidskriftsartikel (refereegranskat)abstract
- Cholesterol has been shown to affect the extent of coronavirus binding and fusion to cellular membranes. The severity of Covid-19 infection is also known to be correlated with lipid disorders. Furthermore, the levels of both serum cholesterol and high-density lipoprotein (HDL) decrease with Covid-19 severity, with normal levels resuming once the infection has passed. Here we demonstrate that the SARS-CoV-2 spike (S) protein interferes with the function of lipoproteins, and that this is dependent on cholesterol. In particular, the ability of HDL to exchange lipids from model cellular membranes is altered when co-incubated with the spike protein. Additionally, the S protein removes lipids and cholesterol from model membranes. We propose that the S protein affects HDL function by removing lipids from it and remodelling its composition/structure.
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| 6. |
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| 7. |
- Correa, Yubexi
(författare)
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Structure of Total High-Density Lipoproteins and Subfractions as a function of lipid serum profile : A Small-Angle X-Ray Scattering study
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- High-density lipoproteins (HDL), also known as "good cholesterol," are essential for preserving cardiovascular health. Understanding the different functions and how each HDL subfraction contributes to general health requires a comprehension of the structural complexity of HDL subfractions. Subpopulations of HDL particles with distinctive lipid and protein contents include HDL2b, HDL2a, and HDL3. These subfractions have various affinities for lipids and cholesterol, which affects how well they mediate reverse cholesterol transport (RCT) and how effective they might be at preventing a therosclerosis. Clarifying these subfractions' unique functions in cholesterol metabolism and cardiovascular prevention requires a thorough investigation of their structural characteristics. Here, we reveal structural details of total HDL fraction and its subfractions by Small-Angle X-ray Scattering (SAXS), a powerful technique to determine particle size, shape, and internal structure without the need for freezing. This property makes SAXS very attractive for analysing the dynamic properties in HDL. Briefly, we found remarkable differences between total HDL (HDLT) and the subpopulations HDL3, HDL2a and HDL2b regarding their biochemical composition and structural characteristics when comparing between individuals presenting a high or low risk of developing cardiovascular disease(CVD).
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