Cardiovascular disease is the leading cause of death worldwide and premature arterial stiffening is a key contributor to this risk. A large body of evidence now points to arterial stiffness as an independent predictor of cardiovascular events. Stiffness can be assessed by a number of indices and is itself affected by factors including mean arterial pressure, vascular smooth muscle tone and structural elements in the vessel wall, such as elastin and collagen. In addition, aging, hypertension, diabetes and hypercholesterolaemia all exacerbate the stiffening process. Stiffness is highly heritable but, despite a clear genetic basis, the precise molecular pathways regulating stiffness are poorly understood. The present review provides an overview of the current literature and examines the evidence that links genetic factors to arterial wall properties. Although the findings support stiffness as a complex genetic trait, the precise nature of the genes contributing to this are still largely unknown. There are a number of candidate genes and many of these could potentially affect the structure and function of the arterial wall. Indeed, it is likely that genes involving signalling pathways and control of the vessel wall matrix will be as important as those involved in the renin–angiotensin system, adrenergic and other vasoactive systems. Identifying the genes involved is important, since it may suggest new biomarkers as well as provide novel drug targets to reduce arterial stiffness. Current pharmacological intervention is simply to reduce blood pressure, but there are emerging therapies; for example, targeted at breaking collagen cross-links or preventing their formation, which are promising new strategies to reduce arterial stiffness and its associated cardiovascular risk.
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June 2008
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Review Article|
May 01 2008
Genetics of arterial structure and function: towards new biomarkers for aortic stiffness?
Yasmin;
1Clinical Pharmacology Unit, Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, U.K.
Correspondence: Dr Yasmin ([email protected]).
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Kevin M. O'shaughnessy
Kevin M. O'shaughnessy
1Clinical Pharmacology Unit, Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, U.K.
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Publisher: Portland Press Ltd
Received:
October 18 2007
Revision Received:
November 30 2007
Accepted:
December 03 2007
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2008 Biochemical Society
2008
Clin Sci (Lond) (2008) 114 (11): 661–677.
Article history
Received:
October 18 2007
Revision Received:
November 30 2007
Accepted:
December 03 2007
Citation
Yasmin, Kevin M. O'shaughnessy; Genetics of arterial structure and function: towards new biomarkers for aortic stiffness?. Clin Sci (Lond) 1 June 2008; 114 (11): 661–677. doi: https://doi.org/10.1042/CS20070369
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