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.