Frontiers in Cardiovascular Drug Discovery: Volume 6

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Title
Copyright
End User License Agreement
Contents
Preface
List of Contributors
Cardiovascular Effects of Ranolazine and the Scope for Translational Research: A Current Review of Literature
Rebecca Pratiti1,*, Parul Sud1, Mohammad Yousef1 and Ankush Moza2
RANOLAZINE
MECHANISM OF ACTION
Effects on Late Sodium Current
Effect on Metabolism
Dosage Formulations, Pharmacodynamics and Pharmacokinetics
Side Effects
General Side Effects
Tolerability of Ranolazine
Drug-drug Interaction
QT-prolonging Effects
Animal Studies
CHRONIC STABLE ANGINA (CSA)
ACUTE CORONARY SYNDROME (ACS)
ATRIAL FIBRILLATION
Rhythm Control for Atrial Fibrillation in the Presence and Absence of other Medications
Post-operative Atrial Fibrillation (POAF) in Patients Undergoing Cardiac Surgery
CARDIOMYOPATHY
Chemotherapy-induced Cardiomyopathy
Hypertrophic Cardiomyopathy
ARRHYTHMIAS
LONG QT SYNDROMES (LQTS 3)
Pathophysiology
Efficacy
HEART FAILURE (HF)
Pathophysiology
Heart Failure with Preserved Ejection Fraction (Diastolic)
Heart Failure With Reduced Ejection Fraction (Systolic)
GLYCEMIC EFFECTS
Mechanism of Action
Effect on Glycated Hemoglobin A1c (HbA1c)
Modifier effect of Metformin
OTHER ADDITIONAL EFFECTS OF RANOLAZINE
FUTURE IMPLICATIONS
Gaps in Translational Research
Possible Causes of Inefficacy in Studies
CONCLUSION AND SUMMARY
LIST OF ABBREVIATIONS
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Rho/Rho Kinase Signaling Pathway and Disease: from Bed to Bench
Yiming Wang1,#, Yuqing Zhang2,# and Dingguo Zhang3,*
INTRODUCTION
BIOLOGICAL EFFECTS OF RHO PROTEIN
Rho Protein Classification
Rho Protein Structure and Activity Regulation
Downstream Effector Molecules of Rho
RHO KINASE
Structure and Classification of Rho Kinases
Regulation Mechanism of Rho Kinase Activity
Rho Kinase Inhibitor
RHO/RHO KINASE AND CARDIOVASCULAR DISEASE
Rho/Rho Kinase and Hypertension
Rho/Rho Kinase and Pulmonary Hypertension
Rho/Rho Kinase and Atherosclerosis
Rho/Rho Kinase and Myocardial Ischemia Reperfusion Injury
Rho/Rho Kinase and Adriamycin-induced Heart Injury
Outlook
RHO KINASE AND ISCHEMIC CEREBROVASCULAR DISEASE
The Mechanism of Rho Kinase in Cerebral Ischemia
Rho Kinase Mediates Oxidative Stress
Rho Kinase Mediated Cytoskeleton Changes
Rho Kinase Mediates Inflammatory Response
Rho Kinase Regulates Phosphatidylinositol Metabolism
Rho Kinase Regulates the Expression of eNOS
Rho Kinase Regulates the Expression of Matrix Metalloproteinase-9
Neuroprotective Effect of Rho Kinase Inhibitor
Outlook
RHO KINASE AND RESPIRATORY DISEASES
Rho Kinase and COPD
Rho Kinase and Asthma
Rho Kinase and IPF
Rho Kinase and Lung Cancer
Conclusion and Prospect
RHO KINASES IN IMMUNE CELLS AND AUTOIMMUNE DISEASES
Rho/ROCK Signaling Pathway in Systemic Lupus Erythematosus
Rho/ROCK Signaling Pathway in Rheumatoid Arthritis
Rho/ROCK Signaling Pathway in Systemic Sclerosis
CONCLUSION
RHO AND CHRONIC KIDNEY DISEASE
Rho/ROCK in 5/6 Nephrectomy and Unilateral Ureteral Ligation Model
Rho/ROCK in Hypertensive Nephropathy Animal Model
Rho/ROCK in Diabetic Animal Model
Rho/ROCK in Contrast Medium Induced Kidney Injury Model
RHO AND PORTAL HYPERTENSION
OUTLOOK
CONCLUSION
ABBREVIATIONS
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Hybernation or Transformation? Challenges in Cardiovascular Drug Development
G. Mercanoglu1,* and F. Mercanoglu2
INTRODUCTION
DEVELOPING NEW DRUGS IN THE 21ST CENTURY
CHALLENGES IN DRUG DEVELOPMENT AND THEIR REFLECTIONS ON THE CARDIOVASCULAR FIELD
DISCOVERY AND DEVELOPMENT
Challenges in Strategic Decision Making
Challenges in Preclinical Trials
CLINICAL DEVELOPMENT
Challenges in Clinical Trials
REGULATORY APPROVAL
Regulatory Uncertainty
Health-related Economic Challenges
FINANCIAL CHALLENGES
Return Potential of Investment
Patent Cliff
Insufficient Incentives (Funding)
Insufficient Investment
Late-stage Failures
CONCLUSION AND FUTURE PERSPECTIVE
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGMENTS
REFERENCES
New Approaches in P2Y12 Receptor Blocker Drugs Use
Dolunay Merve Fakioğlu1 and Sevgi Akaydin1,*
PRIMARY AND SECONDARY HEMOSTASIS
P2Y1 AND P2Y12 (ADP RECEPTORS)
P2Y12 RECEPTOR INHIBITORS AND POTENTIAL CLINICAL USE
Stable Ischemic Heart Disease
Acute Coronary Syndromes
Secondary Prevention of Ischemic Stroke
Prosthetic Heart Valves Triple Treatment
PRECISION MEDICINE IN DUAL ANTIPLATELET REGIMES STRATEGIES (DE-ESCALATION, ESCALATION, CHANGE STRATEGIES FOR DUAL ANTIPLATELET THERAPY)
De-Escalation via a Duration of Dual Antiplatelet Treatment
De-Escalation with Switching Between P2y12 Inhibitors Drugs
De-escalation with Dose Reduction
Escalation
Change Between Prasugrel and Ticagrelor
Triple Antithrombotic Therapy
PRECISION MEDICINE ON P2Y12 INHIBITORS WITH GENE TESTING APPROACH AND CLOPIDOGREL RESISTANCE
P2Y12 Receptor Gene Polymorphisms
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Pathophysiological Links Between Diabetes and Cardiovascular Diseases: at the Biochemical and Molecular Levels
M.M. Towhidul Islam1 and Yearul Kabir1,*
INTRODUCTION
EPIDEMIOLOGICAL STUDIES
STRUCTURAL AND FUNCTIONAL CHANGES OF CARDIAC TISSUE DURING DIABETES
Role of Obesity in Diabetes and CVD
Role of Glycemic Control in Diabetes and CVD
Role of Dyslipidemia in Diabetes and CVD
Role of Hypertension in Diabetes and CVD
BIOCHEMICAL ASPECTS BETWEEN DIABETES AND CVDS
MOLECULAR ASPECTS BETWEEN DIABETES AND CVDS
Genetic Loci Linked with T2DM and CVD
DNA or Histone Modifications in T2DM and CVDs
Association of HMGA1 with T2DM and CVD Risk
Association of MicroRNAs (miRNA) with T2DM and CVD Risk
Association of Long Non-Coding RNA (lncRNAs) with T2DM and CVD Risk
PRIMARY PREVENTION OF CARDIOVASCULAR DISEASE IN DIABETES MELLITUS
LESSONS LEARNED AND FUTURE DIRECTIONS
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Subject Index
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