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Infection and Immunity Feb 2011Bacterial lipoproteins are a set of membrane proteins with many different functions. Due to this broad-ranging functionality, these proteins have a considerable... (Review)
Review
Bacterial lipoproteins are a set of membrane proteins with many different functions. Due to this broad-ranging functionality, these proteins have a considerable significance in many phenomena, from cellular physiology through cell division and virulence. Here we give a general overview of lipoprotein biogenesis and highlight examples of the roles of lipoproteins in bacterial disease caused by a selection of medically relevant Gram-negative and Gram-positive pathogens: Mycobacterium tuberculosis, Streptococcus pneumoniae, Borrelia burgdorferi, and Neisseria meningitidis. Lipoproteins have been shown to play key roles in adhesion to host cells, modulation of inflammatory processes, and translocation of virulence factors into host cells. As such, a number of lipoproteins have been shown to be potential vaccines. This review provides a summary of some of the reported roles of lipoproteins and of how this knowledge has been exploited in some cases for the generation of novel countermeasures to bacterial diseases.
Topics: Bacteria; Cell Membrane; Gene Expression Regulation, Bacterial; Lipoproteins; Virulence
PubMed: 20974828
DOI: 10.1128/IAI.00682-10 -
Progress in Lipid Research Jan 2024Lipoprotein metabolism is critical to inflammation. While the periphery and central nervous system (CNS) have separate yet connected lipoprotein systems, impaired... (Review)
Review
Lipoprotein metabolism is critical to inflammation. While the periphery and central nervous system (CNS) have separate yet connected lipoprotein systems, impaired lipoprotein metabolism is implicated in both cardiometabolic and neurological disorders. Despite the substantial investigation into the composition, structure and function of lipoproteins, the lipoprotein oxylipin profiles, their influence on lipoprotein functions, and their potential biological implications are unclear. Lipoproteins carry most of the circulating oxylipins. Importantly, lipoprotein-mediated oxylipin transport allows for endocrine signaling by these lipid mediators, long considered to have only autocrine and paracrine functions. Alterations in plasma lipoprotein oxylipin composition can directly impact inflammatory responses of lipoprotein metabolizing cells. Similar investigations of CNS lipoprotein oxylipins are non-existent to date. However, as APOE4 is associated with Alzheimer's disease-related microglia dysfunction and oxylipin dysregulation, ApoE4-dependent lipoprotein oxylipin modulation in neurological pathologies is suggested. Such investigations are crucial to bridge knowledge gaps linking oxylipin- and lipoprotein-related disorders in both periphery and CNS. Here, after providing a summary of existent literatures on lipoprotein oxylipin analysis methods, we emphasize the importance of lipoproteins in oxylipin transport and argue that understanding the compartmentalization and distribution of lipoprotein oxylipins may fundamentally alter our consideration of the roles of lipoprotein in cardiometabolic and neurological disorders.
Topics: Humans; Oxylipins; Apolipoprotein E4; Lipoproteins; Nervous System Diseases; Cardiovascular Diseases
PubMed: 37979798
DOI: 10.1016/j.plipres.2023.101265 -
EMBO Molecular Medicine Oct 2014The pathogenesis and progression of atherosclerosis are integrally connected to the concentration and function of lipoproteins in various classes. This review examines... (Review)
Review
The pathogenesis and progression of atherosclerosis are integrally connected to the concentration and function of lipoproteins in various classes. This review examines existing and emerging approaches to modify low-density lipoprotein and lipoprotein (a), triglyceride-rich lipoproteins, and high-density lipoproteins, emphasizing approaches that have progressed to clinical evaluation. Targeting of nuclear receptors and phospholipases is also discussed.
Topics: Anticholesteremic Agents; Arteriosclerosis; Humans; Lipid Metabolism; Lipoprotein(a); Lipoproteins; Lipoproteins, HDL; Lipoproteins, LDL; Models, Biological; Molecular Targeted Therapy; Triglycerides
PubMed: 25172365
DOI: 10.15252/emmm.201404000 -
Journal of the American Heart... Aug 2023Concern continues about whether the measurement of apolipoprotein B (apoB) is adequately standardized, and therefore, whether apoB should be applied widely in clinical... (Review)
Review
Concern continues about whether the measurement of apolipoprotein B (apoB) is adequately standardized, and therefore, whether apoB should be applied widely in clinical care. This concern is misplaced. Our objective is to explain why and what the term "standardization" means. To produce clinically valid results, a test must accurately, precisely, and selectively measure the marker of interest. That is, it must be standardized. Accuracy refers to how closely the result obtained with 1 method corresponds to the result obtained with the standard method, precision to how reproducible the result is on repeated testing, and selectivity to how susceptible the method is to error by inclusion of other classes of lipoprotein particles. Multiple expert groups have determined that the measurement of apoB is adequately standardized for clinical care, and that apoB can be measured inexpensively, using widely available automated methods, more accurately, precisely, and selectively than low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol. ApoB is a standard superior to low-density lipoprotein cholesterol and high-density lipoprotein cholesterol because it is a defined molecule, whereas the cholesterol markers are the mass of cholesterol within lipoprotein particles defined by their density, not by their molecular structure. Nevertheless, the standardization of apoB is being further improved by the application of mass spectrophotometric methods, whereas the limitations in the standardization and, therefore, the accurate, precise, and selective measurement of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol are unlikely to be overcome. We submit that greater accuracy, precision, and selectivity in measurement is a decisive advantage for apoB in the modern era of intensive lipid-lowering therapies.
Topics: Cholesterol, LDL; Cholesterol; Apolipoproteins B; Apolipoprotein B-100; Cholesterol, HDL; Lipoproteins; Apolipoprotein A-I
PubMed: 37489721
DOI: 10.1161/JAHA.123.030405 -
Menopause (New York, N.Y.) Aug 2022During midlife, women experience changes in lipoprotein profiles and deterioration in vascular health measures. We analyzed the associations of groups of lipoprotein...
OBJECTIVE
During midlife, women experience changes in lipoprotein profiles and deterioration in vascular health measures. We analyzed the associations of groups of lipoprotein subfractions as determined by principal component analysis (PCA) with subclinical vascular health measures in midlife women and tested if these associations were modified by menopause status.
METHODS
PCA was used to generate principal components (PCs) from 12 lipoprotein subfractions quantified among 545 midlife women. The associations of the identified PCs and concurrent vascular health measures were assessed using linear or logistic regressions among participants with carotid intima-media thickness (cIMT; n = 259), coronary artery calcium (n = 249), or aortic calcium (n = 248) scores.
RESULTS
PCA generated four PCs representing groups of (1) small, medium, and large very low-density lipoproteins subclasses-very low-density lipoprotein PC; (2) very small, small, and medium low-density lipoprotein (LDL) subclasses-small-medium LDL-PC; (3) large and small high-density lipoproteins subclasses and midzone particles-high-density lipoprotein PC; and (4) large LDL and small intermediate-density lipoproteins-large LDL-PC. Small-medium LDL-PC was positively associated with cIMT, coronary artery calcium, and aortic calcium in unadjusted but not in adjusted models. Menopause status modified the positive association of the small-medium LDL-PC with cIMT (interaction P = 0.02) such that this association was stronger after versus before menopause ( P = 0.01).
CONCLUSIONS
Carotid intimal medial thickening is positively and independently associated with small- and medium-sized LDL particles after menopause. Monitoring levels of specific lipoprotein fractions may have value in identifying midlife women at risk for developing atherosclerotic vascular disease.
Topics: Calcium; Carotid Intima-Media Thickness; Female; Humans; Lipoproteins; Lipoproteins, HDL; Lipoproteins, LDL; Menopause; Middle Aged
PubMed: 35819840
DOI: 10.1097/GME.0000000000001998 -
Microbiology (Reading, England) Mar 2007Lipoproteins are a functionally diverse class of secreted bacterial proteins characterized by an N-terminal lipid moiety. The lipid moiety serves to anchor these... (Review)
Review
Lipoproteins are a functionally diverse class of secreted bacterial proteins characterized by an N-terminal lipid moiety. The lipid moiety serves to anchor these proteins to the cell surface. Lipoproteins are synthesized as pre-prolipoproteins and mature by post-translational modifications. The post-translational modifications are directed by the lipobox motif located within the signal peptide. Enzymes involved in lipoprotein synthesis are essential in Gram-negative bacteria but not in Gram-positive bacteria. Inactivation of genes involved in lipoprotein synthesis attenuates a variety of Gram-positive pathogens, including Mycobacterium tuberculosis. The attenuated phenotype of these mutants indicates an important role of lipoproteins and lipoprotein synthesis in bacterial virulence. M. tuberculosis, the causative agent of tuberculosis, is one of the most devastating pathogens in the world. This article reviews recent findings on the synthesis, localization and function of lipoproteins in mycobacteria.
Topics: Lipoproteins; Mycobacterium
PubMed: 17322184
DOI: 10.1099/mic.0.2006/000216-0 -
Accounts of Chemical Research Oct 2011Over hundreds of millions of years, animals have evolved endogenous lipoprotein nanoparticles for shuttling hydrophobic molecules to different parts of the body. In the... (Review)
Review
Over hundreds of millions of years, animals have evolved endogenous lipoprotein nanoparticles for shuttling hydrophobic molecules to different parts of the body. In the last 70 years, scientists have developed an understanding of lipoprotein function, often in relationship to lipid transport and heart disease. Such biocompatible, lipid-protein complexes are also ideal for loading and delivering cancer therapeutic and diagnostic agents, which means that lipoprotein and lipoprotein-inspired nanoparticles also offer opportunities for cancer theranostics. By mimicking the endogenous shape and structure of lipoproteins, the nanocarrier can remain in circulation for an extended period of time, while largely evading the reticuloendothelial cells in the body's defenses. The small size (less than 30 nm) of the low-density (LDL) and high-density (HDL) classes of lipoproteins allows them to maneuver deeply into tumors. Furthermore, lipoproteins can be targeted to their endogenous receptors, when those are implicated in cancer, or to other cancer receptors. In this Account, we review the field of lipoprotein-inspired nanoparticles related to the delivery of cancer imaging and therapy agents. LDL has innate cancer targeting potential and has been used to incorporate diverse hydrophobic molecules and deliver them to tumors. Nature's method of rerouting LDL in atherosclerosis provides a strategy to extend the cancer targeting potential of lipoproteins beyond its narrow purview. Although LDL has shown promise as a drug nanocarrier for cancer imaging and therapy, increasing evidence indicates that HDL, the smallest lipoprotein, may also be of use for drug targeting and uptake into cancer cells. We also discuss how synthetic HDL-like nanoparticles, which do not include human or recombinant proteins, can deliver molecules directly to the cytoplasm of certain cancer cells, effectively bypassing the endosomal compartment. This strategy could allow HDL-like nanoparticles to be used to deliver drugs that have increased activity in the cytoplasm. Lipoprotein nanoparticles have evolved to be ideal delivery vehicles, and because of that specialized function, they have the potential to improve cancer theranostics.
Topics: Animals; Biological Transport; Biomimetics; Cell Line, Tumor; Humans; Lipoproteins; Molecular Targeted Therapy; Nanoparticles; Neoplasms
PubMed: 21557543
DOI: 10.1021/ar200017e -
Biomolecules Jan 2022Endocytosis is the process by which molecules are actively transported into cells. It can take on a variety of forms depending on the cellular machinery involved ranging... (Review)
Review
Endocytosis is the process by which molecules are actively transported into cells. It can take on a variety of forms depending on the cellular machinery involved ranging from specific receptor-mediated endocytosis to the less selective and actin-driven macropinocytosis. The plasma lipoproteins, which deliver lipids and other cargo to cells, have been intensely studied with respect to their endocytic uptake. One of the first molecules to be visualised undergoing endocytosis via a receptor-mediated, clathrin-dependent pathway was low-density lipoprotein (LDL). The LDL molecule has subsequently been shown to be internalised through multiple endocytic pathways. Dissecting the pathways of lipoprotein endocytosis has been crucial to understanding the regulation of plasma lipid levels and how lipids enter cells in the arterial wall to promote atherosclerosis. It has also aided understanding of the dysregulation that occurs in plasma lipid levels when molecules involved in uptake are defective, as is the case in familial hypercholesterolemia (FH). The aim of this review is to outline the many endocytic pathways utilised for lipoprotein uptake. It explores the various experimental approaches that have been applied to visualise lipoprotein endocytosis with an emphasis on LDL and its more complex counterpart, lipoprotein(a) [Lp(a)]. Finally, we look at new developments in lipoprotein visualisation that hold promise for scrutinising endocytic pathways to finer detail in the future.
Topics: Clathrin; Endocytosis; Humans; Hyperlipoproteinemia Type II; Lipoproteins; Lipoproteins, LDL
PubMed: 35204658
DOI: 10.3390/biom12020158 -
Biomolecules Dec 2021Atherosclerosis is a chronic inflammatory disease that is caused by the accumulation of LDL particles in the intima, causing the activation of immune cells and...
Atherosclerosis is a chronic inflammatory disease that is caused by the accumulation of LDL particles in the intima, causing the activation of immune cells and triggering an inflammatory response. LPS is a potent activator of the innate immune response and it can be transported by lipoproteins. Since humans are much more sensitive to LPS than other mammals, and very low amounts of LPS can elicit an immune response, the aim of this study is to characterize the distribution of LPS and its immunogenic portion (3OHFAs) among lipoprotein types of healthy men. We separated lipoprotein fractions by ultracentrifugation and the amount of each 3OHFA was measured by MS in each lipoprotein fraction to calculate LPS concentration. Lipoprotein particle concentration was measured by NMR. LDL and HDL fractions transported the highest concentration of LPS (35.7% and 31.5%, respectively), but VLDL particles carried more LPS molecules per particle (0.55 molecules/particle) than LDL or HDL ( < 0.01). The distribution of LPS and all 3OHFAs among lipoprotein fractions showed high interindividual variability, suggesting that they may be studied as a potential biomarker. This may help understand the role of LPS in atherosclerosis in those cases where the disease cannot be explained by traditional risk factors.
Topics: Animals; Atherosclerosis; Humans; Lipopolysaccharides; Lipoproteins; Lipoproteins, LDL; Lipoproteins, VLDL; Male; Mammals; Ultracentrifugation
PubMed: 35053195
DOI: 10.3390/biom12010047 -
Molecules (Basel, Switzerland) Jul 2022Lipoproteins are important cardiovascular (CV) risk biomarkers. This study aimed to investigate the associations of lipoprotein subclasses with micro- and macrovascular...
Lipoproteins are important cardiovascular (CV) risk biomarkers. This study aimed to investigate the associations of lipoprotein subclasses with micro- and macrovascular biomarkers to better understand how these subclasses relate to atherosclerotic CV diseases. One hundred and fifty-eight serum samples from the EXAMIN AGE study, consisting of healthy individuals and CV risk patients, were analysed with nuclear magnetic resonance (NMR) spectroscopy to quantify lipoprotein subclasses. Microvascular health was quantified by measuring retinal arteriolar and venular diameters. Macrovascular health was quantified by measuring carotid-to-femoral pulse wave velocity (PWV). Nineteen lipoprotein subclasses showed statistically significant associations with retinal vessel diameters and nine with PWV. These lipoprotein subclasses together explained up to 26% of variation (R2 = 0.26, F(29,121) = 2.80, p < 0.001) in micro- and 12% (R2 = 0.12, F(29,124) = 1.70, p = 0.025) of variation in macrovascular health. High-density (HDL-C) and low-density lipoprotein cholesterol (LDL-C) as well as triglycerides together explained up to 13% (R2 = 0.13, F(3143) = 8.42, p < 0.001) of micro- and 8% (R2 = 0.08, F(3145) = 5.46, p = 0.001) of macrovascular variation. Lipoprotein subclasses seem to reflect micro- and macrovascular end organ damage more precisely as compared to only measuring HDL-C, LDL-C and triglycerides. Further studies are needed to analyse how the additional quantification of lipoprotein subclasses can improve CV risk stratification and CV disease prediction.
Topics: Biomarkers; Cholesterol, LDL; Humans; Lipoproteins; Lipoproteins, LDL; Pulse Wave Analysis; Triglycerides
PubMed: 35897932
DOI: 10.3390/molecules27154760