Katariina Oörni

Katariina Oörni
Wihuri Research Institute | wri · Atherosclerosis Research Laboratory

Ph.D.

About

154
Publications
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4,818
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Additional affiliations
September 1992 - present
Wihuri Research Institute
Position
  • Group Leader

Publications

Publications (154)
Article
Full-text available
Circulating apolipoprotein B-containing lipoproteins, notably the low-density lipoproteins, enter the inner layer of the arterial wall, the intima, where a fraction of them is retained and modified by proteases, lipases, and oxidizing agents and enzymes. The modified lipoproteins and various modification products, such as fatty acids, ceramides, ly...
Article
Background 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 chi...
Article
Objective We recently showed that measurement of the susceptibility of LDL (low-density lipoprotein) to aggregation is an independent predictor of cardiovascular events. We now wished to compare effects of overfeeding different dietary macronutrients on LDL aggregation, proteoglycan-binding of plasma lipoproteins, and on the concentration of oxidiz...
Article
Background There is little knowledge on the effects of alpha-linolenic acid (ALA) and n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) on the LDL lipidome and aggregation of LDL particles. Objective We examined if consumption of Camelina sativa oil (CSO) as a source of ALA, fatty fish (FF) as a source of n-3 LCPUFA and lean fish (LF) as a s...
Article
Full-text available
Objectives: The NLRP3 inflammasome plays a key role in arterial wall inflammation. In this study, we elucidated the role of serum lipoproteins in the regulation of NLRP3 inflammasome activation by serum amyloid A (SAA) and other inflammasome activators. Methods: The effect of lipoproteins on the NLRP3 inflammasome activation was studied in prima...
Article
Background and aims Secretory phospholipase A2 (PLA2) hydrolyzes LDL phospholipids generating modified LDL particles (PLA2-LDL) with increased atherogenic properties. Exocytosis of Weibel–Palade bodies (WPB) releases angiopoietin 2 (Ang2) and externalizes P-selectin, which both play important roles in vascular inflammation. Here, we investigated th...
Article
Full-text available
High density lipoproteins (HDL) are a group of different subpopulations of sialylated particles that have an essential role in the reverse cholesterol transport (RCT) pathway. Importantly, changes in the protein and lipid composition of HDL may lead to the formation of particles with reduced atheroprotective properties. Here, we show that Streptoco...
Article
Full-text available
Circulating low-density lipoprotein (LDL) particles enter the arterial intima where they bind to the extracellular matrix and become modified by lipases, proteases, and oxidizing enzymes and agents. The modified LDL particles aggregate and fuse into larger matrix-bound lipid droplets and, upon generation of unesterified cholesterol, cholesterol cry...
Article
Full-text available
Plasma cholesterol and triglyceride levels are twice as high in hibernating brown bears (Ursus arctos) than healthy humans. Yet, bears display no signs of early-stage atherosclerosis development when adult. To explore this apparent paradox, we analysed plasma lipoproteins from the same ten bears in winter (hibernation) and in summer using size excl...
Article
Background and aims Peripheral artery disease (PAD) is a systemic manifestation of atherosclerosis that is associated with a high risk of major adverse cardiovascular events (MACE). LDL aggregation contributes to atherosclerotic plaque progression and may contribute to plaque instability. We aimed to determine if LDL aggregation is associated with...
Preprint
Background 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 chi...
Article
Background and aims In focal areas of advanced human atherosclerotic lesions, the intimal fluid is acidic. An acidic medium impairs the ABCA1-mediated cholesterol efflux from macrophages, so tending to increase their content of free cholesterol, which is then available for esterification by the macrophage enzyme ACAT1. Here we investigated whether...
Article
Objective: Plant stanol ester supplementation (2-3 g plant stanols/d) reduces plasma LDL (low-density lipoprotein) cholesterol concentration by 9% to 12% and is, therefore, recommended as part of prevention and treatment of atherosclerotic cardiovascular disease. In addition to plasma LDL-cholesterol concentration, also qualitative properties of L...
Article
Full-text available
Background and aims: Genetically modified mice have been used extensively to study human disease. However, the data gained are not always translatable to humans because of major species differences. Liver-humanized mice (LHM) are considered a promising model to study human hepatic and systemic metabolism. Therefore, we aimed to further explore the...
Data
Supporting Information from Minniti et al., Insights From Liver-Humanized Mice on Cholesterol Lipoprotein Metabolism and LXR-Agonist Pharmacodynamics in Humans, Hepatology (2019).
Article
Full-text available
Background: South Asians are more prone to develop atherosclerotic cardiovascular disease (ASCVD) compared with white Caucasians, which is not fully explained by classical risk factors. We recently reported that the presence of aggregation-prone low-density lipoprotein (LDL) in the circulation is associated with increased ASCVD mortality. Objecti...
Article
Full-text available
Low-density lipoprotein (LDL) is considered the major risk factor for the development of atherosclerotic cardiovascular diseases (ASCVDs). A novel and rapid method for the isolation of LDL from human plasma was developed utilising affinity chromatography with monolithic stationary supports. The isolation method consisted of two polymeric monolithic...
Conference Paper
Full-text available
Background and Aims: The strategy to decrease atherosclerosis by stimulating liver X receptor (LXR) originated in mouse models. However, the first human trial testing an LXR agonist was prematurely terminated principally because of severe hyperlipidemia. We therefore investigated whether liver-humanized mice (LHM), i.e. mice repopulated with human...
Article
Atherosclerosis is characterized by low-grade, chronic inflammation, and the balance between pro-inflammatory and inflammation-resolving mechanisms dictates the clinical outcomes. This Review discusses the specific causes of inflammation and the mechanisms underlying the impaired resolution of inflammation that characterize clinically dangerous ath...
Article
Full-text available
Background In randomized trials (SHARP [Study of Heart and Renal Protection], IMPROVE‐IT [Improved Reduction of Outcomes: Vytorin Efficacy International Trial]), combination of statin and ezetimibe resulted in additional reduction of cardiovascular events. The reduction was greater in patients with type 2 diabetes mellitus (T2DM), where elevated re...
Article
Full-text available
Background The focus of studies on high-density lipoproteins (HDL) has shifted from HDL-cholesterol (HDL-C) to HDL function. We recently demonstrated that low USF1 expression in mice and humans associates with high plasma HDL-C and low triglyceride levels, as well as protection against obesity, insulin resistance, and atherosclerosis. Here, we stud...
Data
Data S1. Supplemental methods. Table S1. Lipid Contribution in Lipoprotein Fractions Used in Figure 2 Table S2. Contribution of Different Subclasses for Their Respective Fraction Baseline Table S3. Correlation of Percentage Changes of Proteoglycan (PG) Binding and Lipoprotein Particle Number and Composition Table S4. Safety Assessment Analyses
Article
Background and aims: Omega-3 fatty acids are known to have several cardioprotective effects. Our aim was to investigate the effects of intakes of fish and Camelina sativa oil (CSO), rich in alpha-linolenic acid, on the atherogenic and anti-atherogenic functions of LDL and HDL particles. Methods: Altogether, 88 volunteers with impaired glucose me...
Article
Simvastatin and ezetimibe reduce plasma lipoprotein binding to human arterial proteoglycans in gallstone diseased patients. Ahmed O1,2#, Littmann K1#, Gustafsson U3, Pramfalk C1,4, Öörni K5, Larsson L1, Sahlin S3, Camejo G1, Parini P1,4,6, Eriksson M6 1 Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, Sto...
Conference Paper
Aim: Humans transport plasma cholesterol mainly in LDL, whilst mice are HDL-animals. However, the physiology underlying such difference is still debated. Liver-humanized mice (LHM) carry most of cholesterol in LDL-particles, and uniquely allow to study human liver metabolism and species’ differences. Thus, we aimed to further understand why humans...
Article
Full-text available
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 modifi...
Article
Apolipoprotein B -containing lipoproteins include triglyceride-rich lipoproteins (chylomicrons and their remnants, and very low density lipoproteins and their remnants) and cholesterol-rich low-density lipoprotein particles. Of these, lipoproteins having sizes below 70-80 nm may enter the arterial wall, where they accumulate and induce the formatio...
Article
Background and aims: Subendothelial interaction of LDL with extracellular matrix drives atherogenesis. This interaction can be strengthened by proteolytic modification of LDL. Mast cells (MCs) are present in atherosclerotic lesions, and upon activation, they degranulate and release a variety of neutral proteases. Here we studied the ability of MC...
Article
Background and aims: While inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) is known to result in dramatic lowering of LDL-cholesterol (LDL-C), it is poorly understood how it affects other lipid species and their metabolism. The aim of this study was to characterize the alterations in the lipidome of plasma and lipoprotein parti...
Article
Lipid accumulation is a key characteristic of advancing atherosclerotic lesions. Here we analyzed the ultrastructure of the accumulated lipids in endarterectomized human carotid atherosclerotic plaques using three-dimensional (3D) electron microscopy, a method never used in this context before. 3D-electron microscopy revealed intracellular lipid dr...
Article
Two complementary instrumental techniques were used, and the data generated was processed with advanced numerical tools to investigate the interactions between anti-human apoB-100 monoclonal antibody (anti-apoB-100 Mab) and apoB-100 containing lipoproteins. Partial Filling Affinity Capillary Electrophoresis (PF-ACE) combined with Adsorption Energy...
Data
Two complementary instrumental techniques were used, and the data generated was processed with advanced numerical tools to investigate the interactions between anti-human apoB-100 monoclonal antibody (anti-apoB-100 Mab) and apoB-100 containing lipoproteins. Partial Filling Affinity Capillary Electrophoresis (PF-ACE) combined with Adsorption Energy...
Data
Immunoaffinity procedure was developed for isolation of low density lipoprotein (LDL) from biological samples by using silica-derived immunoaffinity sorbent. Sorbent was prepared by immobilization of monoclonal anti-apoB-100 antibody onto macroporous silica particles, using carefully optimized binding chemistry. Binding capacity of the sorbent towa...
Article
Immunoaffinity procedure was developed for isolation of low density lipoprotein (LDL) from biological samples by using silica-derived immunoaffinity sorbent. Sorbent was prepared by immobilization of monoclonal anti-apoB-100 antibody onto macroporous silica particles, using carefully optimized binding chemistry. Binding capacity of the sorbent towa...
Article
Objective: Activation of the inflammasome pathway in macrophages results in the secretion of 2 potent proinflammatory and proatherogenic cytokines, interleukin (IL)-1β, and IL-18. Atherosclerotic lesions are characterized by the presence of various endogenous activators of the NLR family pyrin domain containing 3 (NLRP3) inflammasome, including ch...
Article
Full-text available
Objective: Apolipoprotein A-I (apoA-I) has been shown to possess several atheroprotective functions, including inhibition of inflammation. Protease-secreting activated mast cells reside in human atherosclerotic lesions. Here we investigated the effects of the neutral proteases released by activated mast cells on the anti-inflammatory properties of...
Poster
Full-text available
To clarify the interactions between monoclonal human anti-apolipoprotein B antibody (anti-apoB) and apoB-containing lipoproteins, neutral double hydrophilic block copolymer capillary coating [1] with partial filling affinity capillary electrophoresis (PF-ACE) was used. The binding processes were studied combined with adsorption energy distribution...
Article
Electronegative LDL (LDL(-)), a modified LDL fraction found in blood, induces the release of inflammatory mediators in endothelial cells and leukocytes. However, the inflammatory pathways activated by LDL(-) have not been fully defined. We aim to study whether LDL(-) induced release of the first-wave proinflammatory IL-1β in monocytes and monocyte-...
Conference Paper
Background: Electronegative LDL (LDL(−)), a modified LDL fraction found in blood, induces the release of inflam-matory mediators in endothelial cells and leukocytes. However, the inflammatory pathways activated by LDL(−) have not been fully defined. We aim to study whether LDL(−) induced release of the first-wave proinflammatory IL-1β in monocytes...
Article
Full-text available
Lipolytic modification of LDL particles by SMase generates LDL aggregates with a strong affinity for human arterial proteoglycans, and may so enhance LDL retention in the arterial wall. Here, we evaluated the effects of apoA-I mimetic peptide 4F on structural and functional properties of the SMase-modified LDL particles. LDL particles with and with...
Article
The accurate spatial distribution of various lipid species during atherogenesis has remained unexplored. Herein, we used time-of-flight secondary ion mass spectrometry (TOF-SIMS) to analyze the lipid distribution in human coronary artery cryosections. The images from the TOF-SIMS allowed visualization of ions derived from individual species of chol...
Article
Full-text available
Atherosclerotic lesions are often hypoxic and exhibit elevated lactate concentrations and local acidification of the extracellular fluids. The acidification may be a consequence of the abundant accumulation of lipid-scavenging macrophages in the lesions. Activated macrophages have a very high energy demand and they preferentially use glycolysis for...
Article
Full-text available
Objective Activated mast cells in atherosclerotic lesions degranulate and release bioactive compounds capable of regulating atherogenesis. Here we examined the ability of activated human primary mast cells to regulate the expression of the major scavenger receptors in cultured human primary monocyte-derived macrophages (HMDMs). Results Components...
Article
Cathepsin G (CatG), a serine protease present in mast cells and neutrophils, can produce angiotensin-II (Ang-II) and degrade elastin. Here we demonstrate increased CatG expression in smooth muscle cells (SMCs), endothelial cells (ECs), macrophages, and T cells from human atherosclerotic lesions. In low-density lipoprotein (LDL) receptor-deficient (...
Article
Objective: To clarify the potential mechanisms by which oxidized low-density lipoprotein (oxLDL) could contribute to the progression of aortic valve stenosis (AVS). Methods: We investigated a total of 46 stenotic and 20 control human aortic valves. The mRNA expression levels of scavenger receptor class A type 1 (SR-A1), CD36, Lectin-like oxidize...
Article
A rigorous processing of adsorption data from quartz crystal microbalance technology was successfully combined with the data obtained by partial filling affinity capillary electrophoresis and molecular dynamics for the clarification of the temperature effect on the interaction of a major glycosaminoglycan chain chondroitin-6-sulfate (C6S) of proteo...
Article
Full-text available
In aortic stenosis plasma lipoprotein-derived lipids accumulate in aortic valves. Here, we first compared the lipid compositions of stenotic aortic valves and atherosclerotic plaque cores. Both pathological tissues were found to be enriched in cholesteryl linoleate, a marker of extracellularly accumulated lipoproteins. In addition, a large proporti...
Article
Objective: Angiopoietin-like 3 (Angptl3) is a regulator of lipoprotein metabolism at least by inhibiting lipoprotein lipase activity. Loss-of-function mutations in ANGPTL3 cause familial combined hypolipidemia through an unknown mechanism. Approach and results: We compared lipolytic activities, lipoprotein composition, and other lipid-related en...
Article
Full-text available
Background: Local acidosis has been demonstrated in ischemic tissues and at inflammatory sites. Results: Acidic extracellular pH triggers NLRP3 inflammasome activation and interleukin-1β secretion in human macrophages. Conclusion: Acidic pH represents a novel danger signal alerting the innate immunity. Significance: Local acidosis may promot...
Article
The feasibility to attach plasma low-density lipoprotein (LDL) particles covalently onto 5μm silica particles and use them as stationary phase in nano-liquid chromatography (nano-LC) for interaction and oxidation studies was clarified. Before the immobilization, both epoxy silica and aldehyde-activated particles were synthesized, LDL was immobilize...