Experimental Physiology
90.3 pp 271-272
DOI: 10.1113/expphysiol.2005.900005
© The Physiological Society 2005
Cardiovascular Genomics
Cardiovascular Genomics Themed Issue
Julian F. R. Paton1 and
Mohan K. Raizada2
1 Department of Physiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK. Email: julian.f.r.paton{at}bris.ac.uk2 Department of Physiology & Functional Genomics, University of Florida College of Medicine, Box 100274, Gainsville, FL 32610-0274, USA. Email: mraizada{at}phys.med.ufl.edu
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Introduction
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 Introduction
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With Experimental Physiology's new remit of Translation and Integration we are delighted to be able to publish a series of articles on the theme of Cardiovascular Genomics. These articles exemplify the use of post-genomic information and employ modern molecular techniques to an integrated system.
Cardiovascular genomics is the study of genes relevant to the function and dysfunction of vital organs that both form and control the cardiovascular system. The purpose of the articles is to provide a current perspective of the molecular approaches that are being adopted to understand the cardiovascular system in both health and disease. The articles cover a broad spectrum of approaches employing genomic and proteomic information as well as the development of novel therapeutic strategies for cardiovascular diseases. The subject matter stretches from basic science to clinical applications and focuses on all components of the cardiovascular system including vessels, heart, kidney and the brain. Various cardiovascular disease states are reviewed. In particular, susceptibility to primary hypertension, a polygenic disease that has long reached worldwide epidemic proportions, appears to be genetically linked. It is notable that many hypertensive patients fail to respond sufficiently to current therapeutic drug strategies to return blood pressure levels to normal values. Surely this indicates that the time is ripe to explore alternate strategies. Cardiovascular genomics is all about doing just that. Knowing the genes that cause susceptibility to cardiovascular diseases could improve treatment. Remarkably, for hypertension little is known about these genes, their function and how they are modulated by stressors and diet. Some of these papers attempt to address these issues by focusing on both the villians and the victims.
About the articles
Within these articles on cardiovascular genomics are methods for identifying genetic traits that relate to cardiovascular disease (Pravenec & Køen). Not surprisingly, over-activity of the renin angiotensin system may well be one of the most wanted villains for cardiovascular disease and polymorphisms of angiotensin type 1 receptors and angiotensin converting enzyme could well cause over-activity of this signalling system (Baudin). An understanding of polymorphisms may also be crucial for the effective design of new drugs as well as successful pharmacotherapy for different patients; these important issues are discussed here including those relating to statins (Johnson & Cavallari).
Clear evidence has emerged that enhancing nitric oxide production reduces both oxidative stress and inflammatory responses that assist in lowering blood pressure but also, independently, that it is beneficial in protecting against cardiac remodelling, renal fibrosis, restenosis and cerebral infarction as exemplified by adeno-associated viral-induced expression of kallikrein, for example (Johnson & Cavallari). The efficacy of gene therapy for safe gene/nucleotide delivery (viral and nonviral) in cerebrovascular diseases has been used to stimulate angiogenesis, over-expression vasodilator agents or break down thrombi and stabilize plaques (Morishita, Aoki & Ogihara). In animal models of cardiovascular disease there has been a rapid expansion of viral vector technology. New strategies of adeno and lenti virus mediated gene transfer include the design and effective use of over-expression and block of specific genes within specific organs (Katovich, Grobe, Huentelman & Raizada). Indeed, as well as tools in basic science somatic gene transfer has clinical applications in the form of gene therapy. Articles include approaches targeted to the coronary and peripheral vascular diseases (Madeddu) as well as cerebral arteries for the treatment of stroke (Watanabe & Heistad).
The articles in this themed issue of Experimental Physiology provide examples of the benefits gleaned from the application of genomic information and technologies to a better understanding of both fundamental physiological processes as well as design of novel therapies for cardiovascular diseases. To extract the full potential from the genome, it will be essential for scientists and clinicians to work collaboratively. Only by sharing ideas, data and resources can we develop the multidisciplinary experimental approaches that will determine the functional relevance of molecular and intracellular processes at the systems level.
