Document Detail


Ageing of the conduit arteries.
MedLine Citation:
PMID:  17200940     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Conduit arteries become stiffer with age due to alterations in their morphology and the composition of the their major structural proteins, elastin and collagen. The elastic lamellae undergo fragmentation and thinning, leading to ectasia and a gradual transfer of mechanical load to collagen, which is 100-1000 times stiffer than elastin. Possible causes of this fragmentation are mechanical (fatigue failure) or enzymatic (driven by matrix metallo proteinases (MMP) activity), both of which may have genetic or environmental origins (fetal programming). Furthermore, the remaining elastin itself becomes stiffer, owing to calcification and the formation of cross-links due to advanced glycation end-products (AGEs), a process that affects collagen even more strongly. These changes are accelerated in the presence of disease such as hypertension, diabetes and uraemia and may be exacerbated locally by atherosclerosis. Raised MMP activity, calcification and impaired endothelial function are also associated with a high level of plasma homocysteine, which itself increases with age. Impaired endothelial function leads to increased resting vascular smooth muscle tone and further increases in vascular stiffness and mean and/or pulse pressure. The effect of increased stiffness, whatever its underlying causes, is to reduce the reservoir/buffering function of the conduit arteries near the heart and to increase pulse wave velocity, both of which increase systolic and pulse pressure. These determine the peak load on the heart and the vascular system as a whole, the breakdown of which, like that of any machine, depends more on the maximum loads they must bear than on their average. Reversing or stabilising the increased arterial stiffness associated with age and disease by targeting any or all of its causes provides a number of promising new approaches to the treatment of systolic hypertension and its sequelae, the main causes of mortality and morbidity in the developed world.
Authors:
S E Greenwald
Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  The Journal of pathology     Volume:  211     ISSN:  0022-3417     ISO Abbreviation:  J. Pathol.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-01-11     Completed Date:  2007-10-15     Revised Date:  2008-04-23    
Medline Journal Info:
Nlm Unique ID:  0204634     Medline TA:  J Pathol     Country:  England    
Other Details:
Languages:  eng     Pagination:  157-72     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2007 Pathological Society of Great Britain and Ireland.
Affiliation:
Pathology Group, Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London. s.e.greenwald@qmul.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Aging / physiology*
Arteries / anatomy & histology,  physiology*
Blood Pressure / physiology
Calcinosis / physiopathology
Elasticity
Elastin / metabolism
Endothelium, Vascular / physiology
Fetal Development / physiology
Glycosylation End Products, Advanced / metabolism
Homocysteine / blood
Humans
Matrix Metalloproteinases / metabolism
Stress, Mechanical
Chemical
Reg. No./Substance:
0/Glycosylation End Products, Advanced; 454-28-4/Homocysteine; 9007-58-3/Elastin; EC 3.4.24.-/Matrix Metalloproteinases
Comments/Corrections
Comment In:
J Pathol. 2008 Mar;214(4):531   [PMID:  18264996 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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