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Advanced Drug Delivery Reviews 2020Lipoproteins (LPs) are circulating heterogeneous nanoparticles produced by the liver and intestines. LPs play a major role in the transport of dietary and endogenous... (Review)
Review
Lipoproteins (LPs) are circulating heterogeneous nanoparticles produced by the liver and intestines. LPs play a major role in the transport of dietary and endogenous lipids to target cells through cell membrane receptors or cell surface-bound lipoprotein lipase. The stability, biocompatibility, and selective transport of LPs make them promising delivery vehicles for various therapeutic and imaging agents. This review discusses isolation, manufacturing, and drug loading techniques used for LP-based drug delivery, as well as recent applications for diagnosis and treatment of cancer, atherosclerosis, and other life-threatening diseases.
Topics: Animals; Drug Delivery Systems; Humans; Lipoproteins
PubMed: 32791075
DOI: 10.1016/j.addr.2020.08.003 -
Free Radical Research Apr 2017Plasma lipoproteins contain variable amounts of lipid oxidation products (LOP), which are known to impair normal physiological functions and stimulate atherosclerotic... (Review)
Review
Plasma lipoproteins contain variable amounts of lipid oxidation products (LOP), which are known to impair normal physiological functions and stimulate atherosclerotic processes. Recent evidence indicates that plasma lipoproteins are active carriers of LOP, low-density lipoprotein (LDL) directing transport toward peripheral tissues, and high-density lipoprotein (HDL) being active in the reverse transport. It has been proposed that the lipoprotein-specific transport of LOP could play a role in atherosclerosis-related effects of LDL and HDL. This article gives an overview of the present knowledge of lipoprotein LOP transport and its association with the risk of atherosclerosis and cardiovascular diseases (CVD). Evidence of the significance of lipoprotein LOP transport comes mainly from studies of physiological oxidative stress and is supported by studies of the functionality apolipoprotein A-1 mimetic peptides. A large body of data has accumulated indicating that lipoprotein LOP transport is connected to the risk of atherosclerosis. While high levels of LOP carried by LDL are indicative of elevated risk, high LOP level in HDL appears to associate with protection. If confirmed, the proposed lipoprotein LOP transport function would affect conception of the etiology of atherosclerosis, but would not conflict current views of the pathophysiological mechanisms. It could open new perspectives, such as the dietary origin of LOP, and the protective function of HDL in clearance of LOP. Focusing on LOP could give additional tools especially for prevention and diagnosis, but would not radically change the management of atherosclerosis and CVD.
Topics: Animals; Atherosclerosis; Cardiovascular Diseases; Humans; Lipids; Lipoproteins; Oxidation-Reduction; Oxidative Stress
PubMed: 28412863
DOI: 10.1080/10715762.2017.1319944 -
American Journal of Kidney Diseases :... Jul 1993The pathways of cellular synthesis, assembly, and secretion of lipoproteins followed by their subsequent intravascular metabolism and cellular uptake provide an... (Review)
Review
The pathways of cellular synthesis, assembly, and secretion of lipoproteins followed by their subsequent intravascular metabolism and cellular uptake provide an efficient system for the transport of exogenous and endogenous lipids. The present report reviews the pathways of normal lipoprotein metabolism and the roles played by specific apoproteins, transfer proteins, enzymes, and cellular receptors in facilitating the transport of lipids in plasma, as well as in the regulation of cellular cholesterol homeostasis.
Topics: Apoproteins; Biological Transport, Active; Chylomicrons; Enzymes; Humans; Lipoproteins; Lipoproteins, HDL; Lipoproteins, LDL; Lipoproteins, VLDL
PubMed: 8322800
DOI: 10.1016/s0272-6386(12)70173-7 -
Annals of Internal Medicine Aug 1991Lipoprotein(a) [Lp(a)], a lipoprotein variant, was relegated for almost 25 years to the study of a few specialists. During the past 3 to 4 years, however, there has been... (Review)
Review
Lipoprotein(a) [Lp(a)], a lipoprotein variant, was relegated for almost 25 years to the study of a few specialists. During the past 3 to 4 years, however, there has been a tremendous upsurge of interest in Lp(a), primarily because of multidisciplinary efforts in structural and molecular biology. Findings emerging from these efforts include the following: Lp(a) represents a cholesteryl-ester, low-density-lipoprotein (LDL)-like particle with apolipoprotein (apo) B-100 linked to apo(a); apo(a) is a glycoprotein coded by a single gene locus on the long arm of chromosome 6, which has several alleles, accounting for its remarkable size polymorphism (300 to 800 kD); apo(a) size polymorphism relates to plasma levels and density distribution of Lp(a); apo(a) is strikingly similar to plasminogen; and in vitro, Lp(a), in appropriate levels, competes for some physiologic functions of plasminogen in the coagulation and fibrinolytic cascade and may thus be thrombogenic. The LDL-like properties of Lp(a) may also confer atherogenic potential, but the mechanisms underlying this atherogenicity remain to be defined. In epidemiologic studies, high plasma Lp(a) levels have been associated with an increased incidence of atherosclerotic cardiovascular disease, especially in patients less than 60 years of age. Moreover, Lp(a) has been found as an intact particle in the arterial intima, particularly in association with atherosclerotic plaque. This finding suggests that Lp(a) can transverse the endothelium, possibly by a non-receptor-mediated process, and, at the intimal level, acquire thrombogenic and atherogenic potentials. Current information justifies the need to determine plasma Lp(a) levels in patients with a history of atherosclerotic cardiovascular disease. Unfortunately, the available techniques need to be standardized. Apolipoprotein(a) exists in isoforms of different sizes, and the importance of determining apo(a) phenotypes in clinical practice remains to be established.
Topics: Arteriosclerosis; Humans; Lipoprotein(a); Lipoproteins; Risk Factors
PubMed: 1829339
DOI: 10.7326/0003-4819-115-3-209 -
Bailliere's Clinical Endocrinology and... Dec 1990
Review
Topics: Apolipoproteins A; Arteriosclerosis; Humans; Lipoprotein(a); Lipoproteins; Thrombosis
PubMed: 2150588
DOI: 10.1016/s0950-351x(05)80086-2 -
Revue Medicale de Bruxelles Feb 1997Since lipids are insoluble in water, they are transported in plasma by lipoproteins composed of several classes of lipids (including cholesterol, triglycerides, and... (Review)
Review
Since lipids are insoluble in water, they are transported in plasma by lipoproteins composed of several classes of lipids (including cholesterol, triglycerides, and phospholipids) and proteins named apolipoproteins. Each class of lipoprotein has a specific function in lipids metabolism. Chylomicrons transport dietary triglycerides and cholesterol from the intestine to peripheral tissues, Very Low Density Lipoproteins (VLDL), are synthetized by the liver to export triglycerides, Low-Density Lipoproteins (LDL) represent a final stage in the catabolism of Very low density lipoproteins and High Density Lipoproteins (HDL) are involved in reverse cholesterol transport. The role of lipoproteins receptors, enzymes, apolipoproteins and transfer proteins is also discussed.
Topics: Apolipoproteins; Biological Transport; Cholesterol; Chylomicrons; Humans; Lipoproteins; Lipoproteins, HDL; Lipoproteins, LDL; Lipoproteins, VLDL; Liver; Triglycerides
PubMed: 9132915
DOI: No ID Found -
Current Opinion in Lipidology Jun 2005The assembly of intestinal lipoproteins is critical for the transport of fat and fat-soluble vitamins. In this review we propose a nomenclature for these lipoproteins... (Review)
Review
PURPOSE OF REVIEW
The assembly of intestinal lipoproteins is critical for the transport of fat and fat-soluble vitamins. In this review we propose a nomenclature for these lipoproteins and have summarized recent data about their intracellular assembly and factors that modulate their secretion.
RECENT FINDINGS
The assembly and secretion of intestinal lipoproteins increases with the augmented synthesis of apoB, apoAIV and lipids. Chylomicron assembly begins with the formation of primordial, phospholipid-rich particles in the membrane, and their conversion to large chylomicrons occurs in the lumen of the smooth endoplasmic reticulum. Chylomicrons are transported from the endoplasmic reticulum via specialized vesicles to the Golgi for secretion. The identification of genetic mutations in chylomicron retention disease indicates that Sar1b may play a critical role in this process. In addition to chylomicron assembly, intestinal cells have been shown to transport dietary cholesterol via apoB-independent pathways, such as efflux.
SUMMARY
Understanding the mechanisms involved in the intracellular transport of chylomicrons and chylomicron-independent secretion pathways are expected to be the next frontiers in the field of intestinal lipoprotein assembly and secretion.
Topics: Biological Transport, Active; Cholesterol; Chylomicrons; Humans; Intestines; Lipoproteins; Terminology as Topic
PubMed: 15891388
DOI: 10.1097/01.mol.0000169347.53568.5a -
Progress in Lipid Research 1991Lipoprotein(a) denotes cholesterol-rich particles similar to low density lipoproteins but characterized by an extra large hydrophilic glycoprotein, Apo(a), added to low... (Review)
Review
Lipoprotein(a) denotes cholesterol-rich particles similar to low density lipoproteins but characterized by an extra large hydrophilic glycoprotein, Apo(a), added to low density lipoproteins. Apolipoprotein(a) is bound to ApoB-100 by a disulfide bridge. Eleven different Apo(a) isoforms of varying sizes coded for by alleles at the Apo(a) gene locus on chromosome 6 have been identified, ranging in Mr between roughly 400-800 kDa. The level of lipoprotein(a) is inversely correlated with isoform size. A strong independent association between high lipoprotein(a) levels and atherosclerotic disorders is documented. Lipoprotein(a) is selectively retained in the intima and engulfed by macrophages in unmodified form. Human Apo(a) is very similar to plasminogen, which suggests that lipoprotein(a) represents a link between atherosclerosis and thrombosis.
Topics: Adult; Arteriosclerosis; Humans; Lipoprotein(a); Lipoproteins; Male; Middle Aged; Thrombosis
PubMed: 1840453
DOI: 10.1016/0163-7827(91)90015-w -
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 -
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