Prevention and Treatment of Atherosclerosis : : Improving State-Of-the-Art Management and Search for Novel Targets.

• Superior document: Handbook of Experimental Pharmacology Series ; v.270
• Author: von Eckardstein, Arnold.
• TeilnehmendeR: Binder, Christoph J.
• Place / Publishing House: Cham : : Springer International Publishing AG,, 2022.; ©2022.
• Year of Publication: 2022
• Edition: 1st ed.
• Language: English
• Series: Handbook of Experimental Pharmacology Series
• Physical Description: 1 online resource (537 pages)

Table of Contents

• Intro
• Preface
• Acknowledgement
• Contents
• Part I: Improving the Treatment of Established Targets
• Diet, Lifestyle, Smoking
• 1 Diet
• 1.1 Dietary Fat (Table 1)
• 1.1.1 Effects on CVD Risk Factors
• 1.1.2 Effects on CVD Events
• 1.2 Dietary Carbohydrates (Table 1)
• 1.2.1 Effects on CVD Risk Factors
• 1.2.2 Effects on CVD Events
• 1.3 Salt (Table 1)
• 1.3.1 Effects on CVD Risk Factors
• 1.3.2 Effects on CVD Events
• 2 Physical Activity
• 3 Smoking
• References
• Blood Pressure-Lowering Therapy
• 1 Introduction
• 2 Non-pharmacological Therapy
• 2.1 Salt Restriction
• 2.2 Reduce Alcohol Intake
• 2.3 Weight Loss and Avoidance of Overweight and Obesity
• 2.4 Regular Physical Activity
• 3 Pharmacological Therapy for the Treatment of Arterial Hypertension
• 3.1 Who Should Be Treated with Pharmacological Therapy?
• 3.2 Choice of Initial Antihypertensive Agents
• 3.3 Combination Therapy
• 3.4 Direct Effects of Antihypertensive Drugs on Atherosclerosis
• 3.4.1 ARBs and ACE Inhibitors
• 3.4.2 Diuretics
• 3.4.3 Calcium Antagonists
• 3.4.4 Beta-Blockers
• 3.4.5 Mineralocorticoid Receptor Antagonists
• 4 Perspectives of Future Antihypertensive Therapy
• 4.1 Unresolved Medical Needs
• 4.2 New Drug Developments
• 4.3 Device Therapy
• 5 Conclusion
• References
• Glycaemic Control in Diabetes
• 1 Cardiovascular Risk in Diabetes
• 2 Microvascular End-Organ Damage and Cardiovascular Risk
• 3 Role of Hyperglycaemia for Micro- and Macro-vascular Complications
• 4 Role of Hyperglycaemia in Reducing Vascular Risks in Type 1 Diabetes
• 5 Efficacy Trials of Glucose Lowering in Type 2 Diabetes
• 6 Cardiovascular Safety Studies in Type 2 Diabetes
• 7 GLP-1 Receptor Agonists (GLP-1-RA)
• 8 SGLT (Sodium Glucose Transporter) 2 Inhibitors
• 9 Mechanisms of Action for Cardio-Renal Protection Through SGLT-2 Inhibition.
• 10 Change in Guidelines and Clinical Recommendations
• 11 Perspectives: Fat Partitioning as a New Target of Diabetes Drugs
• References
• LDL-Cholesterol-Lowering Therapy
• 1 Introduction
• 2 Statins in the Prevention of Cardiovascular Disease
• 3 Non-statin Cholesterol-Lowering Drugs
• 3.1 Ezetimibe
• 3.2 PCSK9 Inhibitors
• 3.2.1 Evolocumab
• 3.2.2 Alirocumab
• 3.3 Lomitapide
• 3.4 Mipomersen
• 4 Cholesterol-Lowering Drugs Under Clinical Development
• 4.1 Inclisiran
• 4.2 Bempedoic Acid
• 5 The Future of Cholesterol Lowering
• 5.1 ANGPTL3-LRx
• 6 Conclusions
• References
• Antithrombotic Therapy: Prevention and Treatment of Atherosclerosis and Atherothrombosis
• 1 Atherogenesis and the Role of Blood Coagulation Components
• 1.1 Blood Coagulation: Impact on Vascular Endothelial Cells
• 1.2 Platelets and Extracellular Vesicles
• 1.3 Antiplatelet Agents and Atherosclerosis
• 1.4 Coagulation Proteases
• 2 From Atherosclerosis to Atherothrombosis
• 3 Antithrombotic Therapy: Clinical Principles and Applications
• 3.1 Single Antiplatelet Agents: Mode of Action and Side Effects
• 3.2 Primary Prevention in the Population
• Selecting the Right Subject?
• 3.3 Primary Prevention in Subjects with Atherosclerosis
• 3.4 Secondary Prevention of Atherothrombosis in Patients with Arterial Vascular Disease
• 4 The Effects of Antithrombotic Therapy on the Vessel Wall and Atherogenesis: Clinical Relevance?
• 5 Novel Antiplatelet and Anticoagulant Targets
• References
• Part II: Novel Drug Developments Addressing Predefined Targets
• Metabolism of Triglyceride-Rich Lipoproteins
• 1 Introduction
• 2 Hepatic Formation and Secretion of VLDL
• 3 Regulators of Hepatic VLDL Secretion
• 4 Synthesis and Secretion of Chylomicrons from the Intestine
• 5 Disorders of the Synthesis of TRLs
• 6 Metabolism of Triglyceride-Rich Lipoproteins.
• 7 Deciphering the Pathogenesis of Hypertriglyceridemia
• 8 Regulation of Hydrolysis of TRLs and the LPL Pathway
• 9 Role of Triglyceride-Rich Lipoproteins in Atherogenesis
• 10 Therapies to Reduce Triglyceride-Rich Lipoproteins
• 11 Development of Novel Interventions
• 12 Conclusion
• References
• High Density Lipoproteins: Is There a Comeback as a Therapeutic Target?
• 1 Introduction
• 2 Possible Reasons for HDL-Cś Clinical Futility
• 2.1 Lack of Causality
• 2.2 Epidemiology and Human Genetics Disprove ``the Higher the Better ́́Concept
• 2.3 Limitations of HDL Modifying Drugs
• 2.3.1 Neither Fibrates nor Nicotinic Acid Specifically Target HDL Metabolism
• 2.3.2 CETP Inhibitors Block Rather than Promote Reverse Cholesterol Transport
• 2.3.3 Combination with High-Intensity Statins: The Winner Takes it All
• 2.4 Wrong Biomarker ``the Good Cholesterol ́́-- 3 Consequences and Perspectives
• 3.1 The Search for Novel HDL-Biomarkers
• 3.2 Ongoing and Novel Drug Developments
• 3.2.1 Reconstituted HDL, apoA-I Mimetic Peptides, and Recombinant LCAT
• 3.2.2 Apabetalone
• 3.2.3 PPAR Modulators
• 3.2.4 ANGPTL3 and Endothelial Lipase
• 3.2.5 ApoC-III Inhibition
• 3.2.6 HDL-C Lowering Therapies: Probucol and Androgens
• 3.3 Other Disease Targets
• 3.3.1 Diabetes
• 3.3.2 Chronic Kidney Disease
• 3.3.3 Infections
• 3.3.4 Autoimmune Diseases
• 3.3.5 Cancer
• 3.3.6 Behind the Blood Brain Barrier: Alzheimerś Disease and Age Related Macular Degeneration
• 3.4 Implications for Nowadayś Clinical Practice
• References
• Lipoprotein(a)
• 1 Introduction
• 2 Sites of Production and Catabolism of Lp(a)
• 3 Physiology and Pathophysiology of Lp(a)
• 4 Genetic Control of Lp(a) Concentrations
• 5 Lp(a) Concentrations and Risk for CVD
• 5.1 Searching for Lp(a) Thresholds Associated with an Increased Coronary Artery Disease Risk.
• 5.2 Lp(a) and Other Vascular Diseases
• 5.3 Differences Between Primary and Secondary Prevention Studies
• 5.4 Is Lp(a) an Independent Risk Factor for CVD?
• 6 What Evidence Do We Have for a Causal Association of High Lp(a) with CVD?
• 7 RNA-Targeting Therapies to Specifically Lower Lp(a)
• 7.1 Antisense Oligonucleotides (ASO) Against Apolipoprotein(a)
• 7.2 Short Interfering RNA (siRNA) to Target Apo(a)
• 8 Other Lipid-Lowering Drugs and Therapies with Possible Influence on Lp(a) Concentrations and Clinical Outcomes
• 8.1 Lipoprotein Apheresis
• 8.2 PCSK9 Inhibitors
• 8.3 Statins
• 8.4 Drugs That Are Probably No Longer Followed for Lp(a)-Lowering Potential
• 9 Therapeutic Lowering of Lipoprotein(a): How Much Is Enough?
• 10 Conclusions
• References
• Nonalcoholic Fatty Liver Disease
• 1 Epidemiology
• 1.1 Definition, Prevalence, and Incidence of NAFLD
• 1.2 Association with Other Diseases
• 1.3 Clinical, Economic, and Social Burden of NAFLD
• 2 Pathophysiology of NAFLD
• 2.1 Intrahepatic Disturbances During NAFLD
• 2.1.1 Lipo- and Glucotoxicity
• 2.1.2 Oxidative Stress and Mitochondrial Dysfunction
• 2.1.3 Hepatic Inflammation and Fibrosis
• 2.2 Metabolic Crosstalk in NAFLD
• 2.3 Genetic Predisposition to NAFLD
• 3 Therapeutics
• 3.1 Dietary/Lifestyle Intervention and Bariatric Surgery
• 3.2 Targeting Lipotoxicity
• 3.3 Targeting Insulin/Glucose Metabolism
• 3.4 Targeting Hepatic Inflammation and Fibrosis
• 3.5 Targeting Bile Acid Metabolism
• 4 Conclusion
• References
• Prevention and Treatment of Atherosclerosis: The Use of Nutraceuticals and Functional Foods
• 1 Introduction
• 2 Red Yeast Rice
• 2.1 Untoward Effects
• 3 Phytosterols and Phytostanols
• 3.1 Untoward Effects
• 4 Berberine
• 4.1 Untoward Effects
• 5 Fiber
• 5.1 Untoward Effects
• 6 Supplements in the Pipeline
• 6.1 Astaxanthin.
• 6.2 Hydroxytyrosol
• 6.3 Probiotics
• 6.4 Bergamot
• 7 Conclusions
• References
• Part III: Hypothesis Based Approaches to Unravel Novel Targets
• Novel Adipose Tissue Targets to Prevent and Treat Atherosclerosis
• 1 Introduction
• 2 Types of Adipose Tissue and Their Impact on Cardiovascular Disease
• 2.1 White Adipose Tissue
• 2.2 Thermogenic Adipose Tissue
• 2.3 Perivascular Adipose Tissue
• 3 Therapies Targeting Adipose Tissue with Proven Clinical Efficacy in the Treatment of Atherosclerosis
• 3.1 Peroxisome Proliferator-Activated Receptor-γ (PPARγ) Agonists
• 3.2 Niacin
• 3.3 Renin-Angiotensin System Blockade
• 4 Novel Therapeutic Targets in Adipose Tissue for Treatment of Atherosclerosis
• 4.1 Promoting Lipoprotein Disposal and Lipid Storage in Adipose Tissues
• 4.2 Boosting Thermogenic Activation
• 4.3 Targeting Inflammation in Adipose Tissue
• 4.4 Hormones Derived from Thermogenic Adipose Tissue
• 4.5 De Novo Lipogenesis-Derived Lipokines
• 5 Future Directions
• References
• Microbiome and Cardiovascular Disease
• 1 Introduction
• 2 Gut and Oral Microbiome Communities: Potential Drivers of ASCVD?
• 2.1 Other Microbiome Community Members
• 2.1.1 Viruses and Bacteriophages
• 3 Microbiome-Derived Metabolites
• 3.1 TMAO
• 3.2 Imidazole-Propionate
• 3.3 Short-Chain Fatty Acids
• 3.4 Other Microbiome-Produced Metabolites Associated with ASCVD
• 4 Bile Acids
• 4.1 Bile Acid Metabolism
• 4.2 Regulation by Bile Acids
• 5 Summary and Future Perspectives
• References
• Smooth Muscle Cell-Proteoglycan-Lipoprotein Interactions as Drivers of Atherosclerosis
• 1 Introduction
• 2 Smooth Muscle Cell Phenotype Switch and Extracellular Matrix Production
• 3 Extracellular Matrix (ECM)
• 3.1 Fibrillar Matrix
• 3.2 Proteoglycans: Non-fibrillar Components of the ECM
• 3.2.1 Versican
• 3.2.2 Biglycan
• 3.2.3 Decorin.
• 3.2.4 Perlecan.