Frontiers in Cardiovascular Drug Discovery: Volume 6

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Title
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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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