Abstract
Cardiovascular disease (CVD) is the most prevalent disease worldwide and there is intense interest in pharmaceutical approaches to reduce the burden of this chronic, aging-related condition. The sirtuin (SIRT) family of NAD+- dependent protein deacetylases and ADP-ribosyltransferases have emerged as exciting targets for CVD management that can impact the cardiovascular system both directly and indirectly, the latter by modulating whole body metabolism. SIRT1-4 regulate the activities of a variety of transcription factors, coregulators, and enzymes that improve metabolic control in adipose tissue, liver, skeletal muscle, and pancreas, particularly during obesity and aging. SIRT1 and 7 can control myocardial development and resist stress- and aging-associated myocardial dysfunction through the deacetylation of p53 and forkhead box O1 (FoxO1). By modulating the activity of endothelial nitric oxide synthase (eNOS), FoxO1, and p53, and the expression of angiotensin II type 1 receptor (AT1R), SIRT1 also promotes vasodilatory and regenerative functions in endothelial and smooth muscle cells of the vascular wall. Given the array of potentially beneficial effects of SIRT activation on cardiovascular health, interest in developing specific SIRT agonists is well-substantiated. Because SIRT activity depends on cellular NAD+ availability, enzymes involved in NAD+ biosynthesis, including nicotinamide phosphoribosyltransferase (Nampt), may also be valuable pharmaceutical targets for managing CVD. Herein we review the actions of the SIRT proteins on the cardiovascular system and consider the potential of modulating SIRT activity and NAD+ availability to control CVD.
Keywords: Cardiovascular disease, aging, sirtuin, SIRT1, NAD+, nicotinamide phosphoribosyltransferase
Current Pharmaceutical Design
Title: NAD+, Sirtuins, and Cardiovascular Disease
Volume: 15 Issue: 1
Author(s): Nica M. Borradaile and J. Geoffrey Pickering
Affiliation:
Keywords: Cardiovascular disease, aging, sirtuin, SIRT1, NAD+, nicotinamide phosphoribosyltransferase
Abstract: Cardiovascular disease (CVD) is the most prevalent disease worldwide and there is intense interest in pharmaceutical approaches to reduce the burden of this chronic, aging-related condition. The sirtuin (SIRT) family of NAD+- dependent protein deacetylases and ADP-ribosyltransferases have emerged as exciting targets for CVD management that can impact the cardiovascular system both directly and indirectly, the latter by modulating whole body metabolism. SIRT1-4 regulate the activities of a variety of transcription factors, coregulators, and enzymes that improve metabolic control in adipose tissue, liver, skeletal muscle, and pancreas, particularly during obesity and aging. SIRT1 and 7 can control myocardial development and resist stress- and aging-associated myocardial dysfunction through the deacetylation of p53 and forkhead box O1 (FoxO1). By modulating the activity of endothelial nitric oxide synthase (eNOS), FoxO1, and p53, and the expression of angiotensin II type 1 receptor (AT1R), SIRT1 also promotes vasodilatory and regenerative functions in endothelial and smooth muscle cells of the vascular wall. Given the array of potentially beneficial effects of SIRT activation on cardiovascular health, interest in developing specific SIRT agonists is well-substantiated. Because SIRT activity depends on cellular NAD+ availability, enzymes involved in NAD+ biosynthesis, including nicotinamide phosphoribosyltransferase (Nampt), may also be valuable pharmaceutical targets for managing CVD. Herein we review the actions of the SIRT proteins on the cardiovascular system and consider the potential of modulating SIRT activity and NAD+ availability to control CVD.
Export Options
About this article
Cite this article as:
Borradaile M. Nica and Pickering Geoffrey J., NAD+, Sirtuins, and Cardiovascular Disease, Current Pharmaceutical Design 2009; 15 (1) . https://dx.doi.org/10.2174/138161209787185742
DOI https://dx.doi.org/10.2174/138161209787185742 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
?Revolutionizing Cancer Treatment: Nano-Therapeutics Targeting Tumor Microenvironment?
This thematic issue explores the forefront of cancer treatment, centering on the groundbreaking potential of nano-therapeutics meticulously designed to target the tumor microenvironment. At its core, the issue aims to unravel the latest advancements in nanotechnology, showcasing innovative materials, formulations, and delivery systems that hold promise for redefining cancer therapeutics. ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Myocardial Quantitative Analysis in Physiological and Pathological Ventricular Hypertrophy: The Increasing Role of Doppler Myocardial Imaging
Current Cardiology Reviews Transcription Factor CHF1/Hey2 Regulates Specific Pathways in Serum Stimulated Primary Cardiac Myocytes: Implications for Cardiac Hypertrophy
Current Genomics Antioxidant Therapy in Diabetic Complications: What is New?
Current Vascular Pharmacology Inhibition of Interleukin-1 in the Treatment of Selected Cardiovascular Complications
Current Reviews in Clinical and Experimental Pharmacology Imaging of Organ Metabolism in Obesity and Diabetes: Treatment Perspectives
Current Pharmaceutical Design Targeted Therapies in Bone Sarcomas
Current Cancer Drug Targets Anticoagulation in Patients with Heart Failure
Cardiovascular & Hematological Agents in Medicinal Chemistry Metabolomics and the Diagnosis of Human Diseases -A Guide to the Markers and Pathophysiological Pathways Affected
Current Medicinal Chemistry Defective Autophagy in Fibroblasts May Contribute to Fibrogenesis in Autoimmune Processes
Current Pharmaceutical Design Erythropoietin and Wnt1 Govern Pathways of mTOR, Apaf-1, and XIAP in Inflammatory Microglia
Current Neurovascular Research Editorial [Hot topic: Crucial Role of Redox Signaling in the Regulation of Heart Health (Guest Editor: Dipak K. Das)]
Current Cardiology Reviews Mitochondrial Toxicity in HAART: An Overview of In Vitro Evidence
Current Pharmaceutical Design Modulators of Inhibitor of Growth (ING) Family Expression in Development and Disease
Current Drug Targets Normal Ventricular Functional Reference Parameters on Magnetic Resonance Imaging in Healthy Children
Current Medical Imaging Folding, Assembly, and Stability of Transmembrane Cytochromes
Current Chemical Biology Acute Kidney Injury in Pediatric Heart Failure
Current Cardiology Reviews Proinflammatory Gene Polymorphisms and Ischemic Stroke
Current Pharmaceutical Design Reductive Stress: A New Concept in Alzheimer’s Disease
Current Alzheimer Research Cytochrome P450 and the Biological Clock in Mammals
Current Drug Metabolism HIV-1 Infection In Children: A Clinical and Immunologic Overview
Current HIV Research