Cholesterol: From Chemistry and Biophysics to the Clinic

Front Cover
Cholesterol: From Chemistry and Biophysics to the Clinic
Copyright
Contents
Contributors
Preface
Afterword
Section 1 Cholesterol chemistry and cell function
Chapter 1 Cholesterol chemistry and laboratory synthesis
Introduction
Cholesterol structural characterization
Cholesterol laboratory synthesis
Cholesterol total synthesis—Historical perspective
Woodward’s cholesterol total synthesis
Robinson’s cholesterol total synthesis
Cholesterol hemisynthesis
Synthesis of ent -cholesterol: The unnatural enantiomer
Concluding remarks
References
Chapter 2 Molecular evolution of cholesterol and other higher sterols in relation to membrane structure
Introduction: The overlooked lipids
Key features of the cholesterol molecule
Evolution and streamlining of a molecule
Phase equilibria in lipid membranes
Cholesterol and lipid membrane phase equilibria: The liquid-ordered phase
Cholesterol, transverse membrane order, permeability, and mechanics
Cholesterol and lateral membrane organization
Other higher sterols: Universality in sterol function
A case study: Cholesterol, lateral membrane structure, and the functioning of Na + /K + -ATPase
Cholesterol and membrane evolution
Acknowledgments
References
Chapter 3 Role of cholesterol in maintaining the physical properties of the plasma membrane
Introduction
Phase diagram for cholesterol/phospholipid mixtures
Basic membrane physical properties and how cholesterol regulates them
Membrane “fluidity”
Order parameter
Rotational diffusion
Direct EPR spectroscopy (continuous-wave EPR)
Saturation recovery EPR (pulse EPR)
Vertical fluctuation
Chol effect on unsaturated bilayers
Small paramagnetic molecules as probes of bilayer properties
Molecular oxygen (a nonpolar probe molecule)
Fe(CN)63 − (a polar probe molecules)
Hydrophobic barriers of lipid bilayer membranes formed by Chol
Properties of polar headgroups
Membrane physical properties at the saturating Chol content (three-dimensional dynamic structure of the lipid-bilayer memb ...
Membrane physical properties at the saturating Chol content in intact PMs
Lateral organization of membranes: Effect of cholesterol
Raft domains
CBDs
New information from the saturation recovery electron paramagnetic resonance stretched exponential function approach
Concluding remarks
Influence of Chol-induced physical properties of lipid bilayers on chemical reactions occurring in the membrane environment
Enhancement of antioxidant action of macular xanthophylls in retina membranes
Maintaining membrane, cell, and organ homeostasis
Summary
Acknowledgments
References
Chapter 4 The fundamental interaction of cholesterol with lipid membranes: The umbrella model
Introduction
Maximum solubility of cholesterol in phosphatidylcholine (PC) and phosphatidylethanolamine (PE) bilayers
The umbrella model
Monte Carlo simulation of chemical potential of cholesterol using multibody interactions
A family of small headgroup molecules: Sterols, ceramides, and diacylglycerols
Molecular dynamics (MD) simulation of the umbrella effect
Measurement of the chemical potential of cholesterol in PC bilayers
Concluding remarks
Acknowledgments
References
Chapter 5 Model peptides and cholesterol
On the energy and entropy parameters of the free energy of the membrane
Acknowledgment
References
Chapter 6 Cholesterol and ceramide: An unlikely pair
Introduction: Membrane heterogeneity
Sphingolipids and cholesterol: Biological impact
Sphingolipids and cholesterol: Membrane biophysics
Sphingolipid biophysics: Ceramides
The context: A tale of displacements
Unveiling the interaction of cholesterol and ceramide
Cholesterol and ceramide in fluid membranes
Lowering Cer and Chol ratios in gel phases
Red blood cell lipid extracts: The simplest of the complex models?
The case for N-acyl sphingolipid variability: Drifting away from canonical C16:0 lipids
Conclusions and future perspectives
Acknowledgments
References
Chapter 7 Cholesterol-recognizing amino acid consensus motifs in transmembrane proteins: Comparative analysis of in silico ...
Introduction
Cholesterol: Bifacial structure, multifaceted functions
Cholesterol footprint on a membrane protein: Starting the investigation
CARC and CRAC algorithms: Basic principles at work
Cholesterol-binding motifs in 3D: What structural studies reveal
Moving to the 3rd dimension
Conclusion
References
Chapter 8 Effects of cholesterol on the GPCR AT1 receptor and its interplay with AT1 antagonists
Introduction
Cholesterol structure
Cholesterol action at membrane and receptor level
Renin-Angiotensin system (RAS) and Hypertension
Cyclodextrins and liposomes as drug delivery systems
Role of the membrane in cholesterol action
Experimental results and their discussion
AT1R antagonists and cholesterol rafts
Cholesterol influence on the physicochemical properties of the cell membrane in the presence of AT1R and sartans
Molecular dynamics (MD) simulations on AT1R embedded in a DPPC:Cholesterol (60:40  mol%) bilayer reveal a putative binding ...
Conclusions
References
Chapter 9 Principles of cholesterol regulation of ion channels
Introduction
Lipids as structural components and functional regulators of membrane proteins
A thermodynamic consideration of lipid-binding sites on ion channels and their generic effects on the gating of the channel ...
Cholesterol-binding sites on ion channels
Cholesterol recognition motifs
Molecular docking of cholesterol to channel proteins
Molecular dynamics simulations to identify cholesterol-binding sites and differentiate structural and regulatory sites
Functional impact of cholesterol on the activities of ion channels
Experimental techniques and systems for studying cholesterol-channel interactions
Cholesterol-regulation of a set of typical ion channels
Large-conductance Ca-sensitive K + channels (BK)
Inwardly rectifying K + channels (Kir)
Functional regulations of AChR by cholesterol in membranes
Cholesterol-dependent gating effects on voltage-gated ion channels
Technical limitations and potential solutions for further developments
Conclusions
Acknowledgments
References
Chapter 10 Fluorescent probes for microscopy visualization of cholesterol topography and dynamics in membranes
Introduction
The elusive ideal probe
Cholesterol probes
Indirect cholesterol probes
Filipin
Perfringolysin O
Direct imaging of intrinsic fluorescent cholesterol analogs
Dehydroergosterol and cholestanetriol
Organic dye Chol probes
NBD-Chol
fPEG derivatives
Pyrene derivatives
BODIPY derivatives
TopFluor cholesterol
Dansyl-cholestanol
Rhodamine-cholestanol
Imidazolium-based cholesterol (CHIM) analogs
Concluding remarks
Acknowledgments
Author contributions
Declaration of interests
References
Chapter 11 Cholesterol transport in blood, lipoproteins, and cholesterol metabolism
Introduction
Lipoproteins an overview
Exogenous cholesterol metabolism: Cholesterol derived from diet
Endogenous cholesterol metabolism: Synthesized cholesterol
Low-density lipoprotein cholesterol
High-density lipoprotein cholesterol
How does aging impact cholesterol metabolism?
Obesity and aging: Two sides of the same coin?
Using mathematical modeling to explore cholesterol metabolism
Discussion of future perspectives
Author contributions
References
Chapter 12 Common laboratory research methods for detection and quantification of cholesterol
Introduction to cholesterol detection and quantification
The early era of cholesterol detection and quantification: Colorimetric approaches
MS-based approaches
Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS)
Electrospray ionization tandem mass spectrometry (ESI-MS/MS)
Matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS)
Ambient ionization mass spectrometry (AIMS), desorption electrospray ionization mass spectrometry (DESI-MS), and direct ana ...
Imaging-based approaches
The Liebermann-Burchard reaction-based visualization of cholesterol
MS-based imaging
Cholesterol-sensitive fluorescent dye filipin
Cytolysins
Antibody-based approaches
Enzymatic methods
Colorimetric sensing
Fluorometric sensing
Summary and concluding remarks
References
Chapter 13 Approaches for modifying cellular cholesterol levels and their application to mechanistic studies: Examples from ..
Introduction
In vitro methods for modifying cholesterol levels in cell membranes
Alteration of cholesterol levels in Xenopus oocytes
Phospholipid-based liposomes as a means to increasing the level of cholesterol in Xenopus oocytes
The use of methyl- β -cyclodextrin (M β CD) to alter the level of cholesterol in Xenopus oocytes
Alteration of cholesterol levels in tissues and cells other than Xenopus oocytes
β -cyclodextrins as means for altering cholesterol content in tissues and cells other than Xenopus oocytes
Lipoproteins: Preincubated plasma, low-density lipoprotein (LDL), and high-density lipoprotein (HDL)
Water-soluble cholesterol
In vivo modification of cholesterol levels
Cholesterol altering diets
High-cholesterol/high-fat diet
Plant sterol/plant stanol diet
Cholesterol-lowering drugs
Statins
Cholesterol absorption inhibitors (ezetimibe)
Bile acid sequestrants
Fibric acid derivatives
Applications to mechanistic studies on the effect of cholesterol on ion channel targets
Applying controls in studies on the effect of cholesterol on protein function: Specific examples from the potassium channel ...
Establishing the effect of cholesterol on G-protein gated inwardly rectifying potassium channels using different approaches ...
Establishing the effect of mutations on the sensitivity of inwardly rectifying potassium channels in Xenopus oocytes (lip ...
Controlling for M β CD treatment through the application of M β CD/cholesterol: Effect of cholesterol depletion on atrial G ...
Establishing the effect of in vivo modifications of cholesterol levels: Effect of a high-cholesterol diet and cholesterol l ...
Establishing the effect of cholesterol in whole organ: Application of lipoproteins and cyclodextrins in studies of ion cha ...
Outlook
References
Section 2 Cholesterol homeostasis and its disruption
Chapter 14 Diet-induced hypercholesterolemia in small laboratory animal models
Introduction
Mouse models
Rat models
Hamsters
Guinea pigs
Rabbits
Additional diet considerations
Control diets
References
Chapter 15 Nutrition and cholesterol metabolism
Introduction
Cholesterol structure
Nutritional recommendations for maintaining healthy blood cholesterol levels
Dietary Guidelines for Americans
Dietary cholesterol intake
Saturated fat intake
Cholesterol functions
Digestion and absorption of cholesterol
Transport of cholesterol
Endogenous cholesterol synthesis
Blood cholesterol and atherosclerosis
Guinea pigs as a preclinical model
Advances in cholesterol research
Dietary cholesterol and heart disease
Patients with prediabetes, diabetes, or metabolic syndrome
Patients with cardiovascular disease
Populations with hypercholesterolemia
Healthy individuals
Findings from systematic reviews and metaanalysis
Explanatory and predictive models approach
Conclusions
Acknowledgments
References
Chapter 16 Cholesterol and early development
Introduction
The fetus and cholesterol
Fetal cholesterol synthesis
Cholesterol and fetal development
Fetal cholesterol derivates and metabolites
Steroid hormones
Calcitriol
Oxysterols
Bile acids
Steroid hormones in reproduction and early life
Sex steroid hormones and selected reproductive organs
Ovaries
Uterus
Testes
Fetal adrenal glands and steroid hormone production
Extraembryonic structures, secondary yolk sac and placenta, and materno-fetal cholesterol transport
Vitelline circulation
Chorionic circulation
Maternal cholesterol levels in healthy pregnancies, maternal hyper- and hypocholesterolemia, and consequences for the fetus
Maternal cholesterol levels in healthy pregnancies
Supraphysiological hypercholesterolemia
Hypocholesterolemia
Effect of selected medicines related to cholesterol metabolism on the fetal development
Ursodeoxycholic acid (UDCA)
Colesevelam
Statins
Ezetimibe
Fibrates
Niacin
Summary
References
Chapter 17 Clinical and biochemical diagnostic methods: What do blood lipid levels tell us?
Introduction
Separation of plasma lipoproteins
Use of conventional laboratory methods to measure lipoproteins by determining their cholesterol content
Beyond standard lipid profiles: Determination of atherogenic lipoproteins by advanced lipoprotein testing
Triglyceride-rich lipoprotein remnants and ASCVD risk
Determination of lipoprotein (a) cholesterol
Determination of lipoprotein X
Fasting versus nonfasting lipid measurements
Lipid and lipoprotein testing in laboratory animals
What do lipid/lipoprotein levels tell us?
References
Chapter 18 Familial hypobetalipoproteinemia and abetalipoproteinemia
Introduction
ApoB gene mutations causing familial hypobetalipoproteinemia
Familial hypobetalipoproteinemia (FHBL) and coronary heart disease (CHD)
FHBL and hepatic steatosis
FHBL and insulin sensitivity
FHBL, hepatic cirrhosis, and hepatocarcinoma
FHBL and psychiatric disease
Heterozygous FHBL and neurological manifestations
Proprotein convertase subtilisin kexin 9 gene (PCSK9) mutations
Familial combined hypolipidemia (FHBL2)
Angptl3 S17x
Abetalipoproteinemia (ABL) and homozygous hypobetalipoproteinemia (HHBL)
Diagnosis and management
Homozygous FHBL, compound heterozygous FHBL and abetalipoproteinemia
Heterozygous FHBL
Pregnancy management
Conclusion
References
Chapter 19 Critical illness and cholesterol levels
Introduction
Cholesterol is crucial for several reasons
The mechanisms of cholesterol depletion
Clinical implications of hypocholesterolemia
Cholesterol metabolism and trauma
The complex character of hypocholesterolemia in trauma
Cholesterol metabolism and inflammation
Depletion of serum cholesterol in surgical patients and in sepsis
Cholesterol metabolism during bleeding and fluid resuscitation
Hypocholesterolemia in critical conditions and on artificial pulmonary ventilation resulting from pneumonia
Acknowledgments
References
Chapter 20 Familial hypercholesterolemia
Introduction
Genetic and molecular background of FH
Low-density lipoprotein receptor (LDLR)
Apolipoprotein B (APOB)
Protein convertase subtilisin kexin (PCSK9)
Low-density lipoprotein receptor adaptor protein-1 (LDLRAP1)
Other genes
Polygenic familial hypercholesterolemia
Familial hypercholesterolemia diagnosis
Familial hypercholesterolemia treatments
Statins
Nonstatin treatments
Ezetimibe
PCSK9 inhibitors
Bile acid sequestrants
Niacin
Low-density lipoprotein aphaeresis
Lomitapide and Mipomersen
Other therapies
Nutrition and familial hypercholesterolemia
Management of homozygous familial hypercholesterolemia
Familial hypercholesterolemia-related diseases
Familial hypercholesterolemia and cardiovascular disease
Familial hypercholesterolemia and type 2 diabetes mellitus
Familial hypercholesterolemia and risk of chronic kidney disease
Familial hypercholesterolemia current status and future perspectives
References
Chapter 21 Niemann-Pick type C disease (NPC)
Introduction
Structure and function of the lysosome: The term of a lysosomal disease
Clinical picture of NPC disease
Genetic background of NPC
NPC1 gene
NPC2 gene
Genotype-phenotype correlation
Biochemical aspects of NPC1 and NPC2 proteins
Pathomechanisms underlying NPC disease
Diagnostics
Histologic findings
Filipin staining
Oxysterols
Lysosphingolipids
Metabolites of bile acids
Chitotriosidase
Heat shock protein 70 (HSP70)
Genetic analyses
Treatment
Acknowledgment
References
Chapter 22 Rare monogenic disorders of cholesterol metabolism
Introduction
Monogenic hypercholesterolemia
Autosomal dominant hypercholesterolemia
Familial hypercholesterolemia
Rare forms of autosomal dominant hypercholesterolemia
APOE gene
STAP1 gene
Recessive hypercholesterolemia
Autosomal recessive hypercholesterolemia (ARH)
Sterol storage diseases
Plasma noncholesterol sterols
Sitosterolemia
Bile acid biosynthesis disorders
Major pathways for excretion of cholesterol into bile
Inborn errors of bile acid synthesis
Cerebrotendinous xanthomatosis
Hypercholesterolemia due to cholesterol 7 α -hydroxylase deficiency
Hypocholesterolemia
Primary hypobetalipoproteinemia
Abetalipoproteinemia
Familial hypobetalipoproteinemia
PCSK9 deficiency
Chylomicron retention disease
Familial combined hypolipidemia
Other inherited disorders associated with hypocholesterolemia
Primary bile acid malabsorption
Smith-Lemli-Opitz syndrome
Other potential genetic causes of hypocholesterolemia
NPC1L1 gene
IDOL gene
LIMA1 gene
References
Chapter 23 Secondary (acquired) hypercholesterolemia
Introduction
Causes of secondary hyperlipidemias and their treatment
Diet and lifestyle
Insulin resistance, metabolic syndrome, and obesity
Diabetes mellitus
Hypothyroidism
Nephrotic syndrome
Chronic kidney disease
Multiple myeloma
Medications
Conclusions
References
Chapter 24 Blood lipids and molecular pathways of atherogenesis
Introduction
Cholesterol metabolism
Pathophysiology of atherosclerosis
Low-density lipoprotein cholesterol and cardiovascular disease
Oxidized low-density lipoprotein cholesterol and cardiovascular disease
Small dense low-density lipoprotein cholesterol and cardiovascular disease
High-density lipoprotein cholesterol: Marker or risk factor?
Triglycerides and cardiovascular disease
Genetics and dyslipidemia
Conclusions
References
Chapter 25 Lysosomal acid lipase: Roles in rare deficiency diseases, myeloid cell biology, innate immunity, and common neut...
Historical background: Lysosomal acid lipase (LAL)
Structure, properties, and biology of LAL
LAL homology with other lipases and structure
Cellular expression of LAL
Central nervous system cholesterol metabolism
Roles of LAL in visceral neutral lipid metabolism, inflammation, and immune system
Roles of LAL in catabolic and anabolic cellular networks
Critical role(s) of LAL in myeloid cell differentiation and function
The role of LAL in T cell development, function, and T cell responses to graft versus host disease (GVHD)
LAL roles in disease states
Lysosomal acid lipase deficiency diseases (LALDs)
Rpi-Lald
Ca-Lald
Pathology
Liver
Molecular biology and genetics
Population prevalence
LIPA mutations and function
LIPA mutations and effects
Treatment of LALD variants
Diet and supportive care
Rpi-Lald
Ca-Lald
Specific LAL therapy in LALDs
LAL in diseases beyond the LALDs
LAL and nonobese nonalcoholic fatty liver disease, NAFLD/NASH
The role of LAL on endothelial cell proliferation, migration, and angiogenesis
LAL: Tumor progression, metastasis, and tumor microenvironment
LAL hydrolyzes retinyl esters (RE)
LAL in atherosclerosis
References
Further reading
Chapter 26 Cholesterol and pathogens
Introduction
The role of cholesterol-rich membrane microdomains in infectious diseases
Cholesterol recruitment to pathogen-containing vacuoles
Targeting cellular cholesterol metabolism
Systemic cholesterol levels and pathogens
Cholesterol-lowering agents as potential therapeutics in infectious diseases
Cholesterol and immune response
Summary
Acknowledgments
References
Chapter 27 Involvement of cholesterol and β -amyloid in the initiation and progression of Alzheimer’s disease
Neurodegenerative diseases are a significant health problem: Alzheimer’s disease (AD)
The amyloid cascade as a central cause for Alzheimer’s disease
Cellular domains important for the formation of A β and cholesterol
Interactions of A β with the neuronal membrane and the initiation of synaptic failure
Participation of membrane lipids in the initiation of A β -mediated neurotoxicity
How A β and cholesterol might lead to neurodegeneration
Cholesterol affects a number of membrane proteins that fine tune neuronal excitability
The ε 4 isoform (ApoE4) factor in disease onset and progression
References
Chapter 28 Cholesterol and alcohol
Introduction
Alcohol pharmacology
Alcohol use disorder
Alcohol and cholesterol interactions
Alcohol and lipoproteins
Vldl
Ldl
Hdl
Alcohol and PCSK9
PCSK9 biology
PCSK9 and cholesterol regulation
PCSK9 and alcohol effects
Fetal alcohol spectrum disorders (FASDs) and cholesterol
Targeting lipids for treatment of alcohol-related diseases
Statin therapy
PCSK9 monoclonal antibody therapy
PCSK9 RNAi therapy
Conclusion
References
Section 3 Pharmacological considerations and perspectives
Chapter 29 Cholesterol stiffening of lipid membranes and drug interactions: Insights from neutron spin echo and deuterium N...
Introduction
Neutron spin echo spectroscopy of lipid membranes
Neutron spin echo principles
Neutron spin echo technique
Membrane undulations
Membrane thickness fluctuations
Solid-state 2 H NMR spectroscopy of lipid membranes
Solid-state 2 H NMR spectroscopic principles
Membrane dynamics and structural properties by solid-state 2 H NMR spectroscopy
Membrane stiffening effect of cholesterol from molecular dynamics simulations
Cholesterol effects on drug uptake and drug delivery applications
Conclusions
Acknowledgment
References
Chapter 30 Cholesterol in drug delivery systems
Introduction
The common synthesis chemistry of modifying cholesterol into the polymers
Polymerization of cholesterol-based monomers
Postpolymerization modification strategy to introduce cholesterol
Cholesterol in the form of drug delivery vehicles
Cholesterol and its derivatives in liposomes
PEGylation and dePEGylation
Ligand modification
Cationic modification
Self-assembling cholesterol amphiphilic polymers into nanostructures
Cholesteryl albumins
Cholesteryl natural carbohydrate nanostructures
Cholesteryl synthetic polymer conjugates
Cholesteryl drug on gene conjugates
Cholesteryl derivatives for macromolecules delivery
Conclusion
References
Chapter 31 Modification of vascular receptor pharmacology by cholesterol: From molecular determinants to impact on arterial...
Introduction
Cholesterol modulation of vasoactive drug action in which the underlying pharmacodynamic process(es) is not fully determine ...
Cholesterol modulation of vasoactive drug action occurring at the cell membrane where the vasoactive drug receptor of inter ...
Cholesterol modulation of vasoactive drug action occurring at the vasoactive drug receptor protein itself
Metabolotropic receptors: The human β 2 -adrenergic receptor
Ionotropic receptors: BK channels
Conclusions and prospective
References
Chapter 32 Clinical strategies for reducing cholesterol levels
Introduction
Epidemiology
Risk factors for hyperlipidemia
Modifiable risk factors
Nonmodifiable risk factors
Secondary causes of elevated LDL-C (some examples appear below; refer to the “ Clinical pearls ” section of this chapter fo ...
Further risk assessment
Genetics
Major guidelines for lipid-lowering therapy in the United States
National Lipid Association (NLA) recommendations for patient-centered management of dyslipidemia: Parts 1 and 2 (2015)
Part 1
Part 2
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: Executive su ...
A report of the American College of Cardiology (ACC)/American Heart Association (AHA) Task Force on Clinical Practice Guide ...
2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: Executive summary
A report of the American College of Cardiology (ACC)/American Heart Association (AHA) Task Force on Clinical Practice Guide ...
Consensus statement by the American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology ( ...
Cardiovascular disease and risk management from the American Diabetes Association (ADA) 2021 standards of medical care in d ...
Pharmacologic treatment of lipids
Statins
Limitations of statins
Nonadherence to statin treatment
Statin intolerance
Statin resistance
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors
Inclisiran (interfering RNA therapy directed against PCSK9)
Icosapent ethyl
Cholesterol absorption inhibitors (ezetimibe)
Bile acid sequestrants
Niacin
Fibrates
Adenosine triphosphate-citrate lyase (ACL) inhibitors (bempedoic acid)
Cholesteryl ester transfer protein (CETP) inhibition
Angiopoietin-like 3 (ANGPL3) inhibitors (evinacumab)
Other lipid-lowering therapies
Lomitapide
Mipomersen
Volanesorsen
Lifestyle therapies
Nonprescription and dietary supplements
Omega-3 fatty acids
Red yeast rice
Soluble fiber
Phytosterols
Coenzyme Q
Policosanol
Resveratrol
Patient education
Clinical pearls
Hypothyroidism
Lysosomal acid lipase deficiency (LALD)
Screening for lipid disorders
Limitations of risk calculators
Secondary causes of dyslipidemia
Summary
References
General patient education resources for understanding cholesterol disorders and treatment options
Clinician tools
Further reading
Chapter 33 Medicinal chemistry and pharmacology of statins
Introduction
Medicinal chemistry of statins
Early search for inhibitors of cholesterol biosynthesis
3-Hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA reductase)
First-generation statins
Second-generation statins
Pharmacology
Mechanism of action
Pharmacokinetics (ADME)
Adverse effects and drug interactions
Decreasing efficacy with increased statin dose—Proprotein convertase subtilisin/kexin type 9 (PCSK9) induction
Future drugs and concluding remarks
References
Chapter 34 Cyclodextrins as promising therapeutics against cholesterol overload
Introduction
Cyclodextrins in general
Structure and major applications of cyclodextrins
Cyclodextrins as compounds to selectively modify cholesterol levels of biological membranes
Direct cyclodextrin actions on proteins
Cyclodextrins in the treatment of Niemann-Pick type C disease
Clinical symptoms and cellular pathophysiology of Niemann-Pick type C disease
Possible mechanisms of CD actions in Niemann-Pick type C disease
Clinical experience with HP β CD in NPC
Alternatives of HP β CD in the treatment of NPC
Future perspectives using new β CD-based variations in NPC
Cyclodextrins with great potential in the treatment of neurodegenerative diseases
Alzheimer’s disease
Transmissible spongiform encephalopathies (prion diseases)
Parkinson’s disease
Cyclodextrins as promising therapeutics in atherosclerosis
Role of cyclodextrins in the treatment of kidney diseases
Role of cyclodextrins in the treatment of eye disorders
Potential effects of cyclodextrins against coronavirus
Concluding remarks
Acknowledgments
References
Chapter 35 Hyperlipidemia and rheumatoid arthritis
Introduction
Pathophysiologic mechanisms in rheumatoid arthritis (RA)
Articular and extra-articular manifestations of RA
Rheumatoid arthritis treatment
Comorbidities in RA
CVD: A major comorbidity in RA
CVD risk assessment in RA
CVD and atherosclerosis in RA
Lipid profile in RA patients
Mechanisms related to dyslipidemia in RA
Lipid concentration and inflammatory markers
Atherosclerosis and inflammation
Lipid metabolism and inflammation
The impact of cytokines on LDL
Lipid peroxidation
Altered HDL function and structure
Effects of antirheumatic therapy on serum lipid levels
Glucocorticoids (GCs)
DMARDs
Antitumor necrosis factor-alpha (anti-TNF-a) agents
Anti-interleukin-6 (IL-6) agents
Janus kinase inhibitors (JAK inhibitors)
Other agents
Mediterranean diet and RA
The role of exercise in RA
Conclusions
References
Chapter 36 Management of hypercholesterolemia in individuals living with HIV/AIDS
Introduction
Antiretroviral therapy and hyperlipidemia
Protease inhibitors (PIs)
Nucleoside reverse transcriptase inhibitors (NRTIs)
Nonnucleoside reverse transcriptase inhibitors (NNRTIs)
Integrase inhibitors (INSTIs)
Why management of HIV dyslipidemia needs the specialist’s input?
Cardiovascular risk and HIV
Diabetes mellitus, metabolic syndrome and HIV
Nonalcoholic fatty liver disease and HIV
Chronic kidney disease among HIV patients and associated dyslipidemia
Hypothyroidism and HIV
Excess alcohol intake
Aging with HIV
Solutions for hyperlipidemia in HIV patients
Life style changes and intervention (weight loss, physical activity, and change in diet)
Statin therapy, when to treat and interaction with ART medications
Why HIV metabolic clinic should be integral part of HIV service?
Conclusion
References
Index
Back Cover