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Impaired abdominal aortic wall integrity in elderly men carrying the angiotensin-converting enzyme D allele
Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Physiology.
Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences.
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2011 (English)In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 42, no 3, 309-316 p.Article in journal (Refereed) Published
Abstract [en]

Objective: A genetic polymorphism in the angiotensin-converting enzyme gene (ACE I/D polymorphism) has been associated with abdominal aortic aneurysm and a link between aortic aneurysm and aortic stiffness has been suggested. The aim of this study was to explore the links between ACE I/D polymorphism, circulating ACE, and abdominal aortic wall integrity as reflected by abdominal aortic wall stiffness.

Material: The study population consisted of 406 subjects (212 men and 194 women) aged 70-88 years.

Methods: The mechanical properties of the abdominal aorta were determined 3-4 cm proximal to the aortic bifurcation using a Wall Track System. ACE-genotype was determined by PCR followed by gel electrophoresis, and circulating ACE level was measured by ELISA.

Results: Men carrying the ACE D allele had lower distensibility coefficient than II carriers (ID/DD 8.09 vs II 10.38, P=0.017). Multiple regression analyses showed additional associations between the ACE D allele and increased stiffness β as well as reduced cross-sectional compliance.

Conclusion: This study showed that men carrying the ACE D allele have stiffer abdominal aortas compared to II carriers. Deranged abdominal aortic stiffness indicates impaired vessel wall integrity, which along with other local predisposing factors, may be of importance in aneurysmal disease.

Place, publisher, year, edition, pages
Elsevier , 2011. Vol. 42, no 3, 309-316 p.
Keyword [en]
Aorta; Arterial stiffness; Distensibility; Gene polymorphism; Mechanical properties
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-67213DOI: 10.1016/j.ejvs.2011.04.010ISI: 000295061800007OAI: oai:DiVA.org:liu-67213DiVA: diva2:408323
Available from: 2011-04-04 Created: 2011-04-04 Last updated: 2013-09-26Bibliographically approved
In thesis
1. Angiotensin-converting enzyme in cardiovascular function and dysfunction
Open this publication in new window or tab >>Angiotensin-converting enzyme in cardiovascular function and dysfunction
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Angiotensin-converting enzyme (ACE) is a key enzyme in the renin-angiotensin system, converting angiotensin I to the vasoactive peptide angiotensin II, and degrading bradykinin. Angiotensin II is a multifunctional peptide, acting on a number of different tissues. A common genetic variation in the gene encoding ACE; ACE I/D polymorphism influences the level of ACE in the circulation, and has been linked to increased risk for cardiovascular disease. This thesis aimed to explore the connection between ACE and cardiovascular function and dysfunction.

The impact of nicotine and nicotine metabolites on ACE in cultured human endothelial cells was studied. Nicotine as well as nicotine metabolites induced increased ACE activity in cultured human endothelial cells. In elderly men a higher ACE level was seen in smokers compared to non-smokers. Furthermore, diabetes was associated with higher circulating ACE. Increased ACE level may represent a cellular mechanism which contributes to vascular damage.

Elderly men carrying the ACE D allele had higher abdominal aortic stiffness compared to men carrying the I/I genotype. Our data suggest that the mechanism by which the ACE D allele modulates aortic wall mechanics is independent of circulating ACE levels. Previous studies have indicated a link between the D allele and abdominal aortic aneurysm. Increased aortic stiffness suggests impaired vessel wall integrity, which combined with local hemodynamic and/or inflammatory factors may have a role in aneurysm formation.

Subjects with left ventricular dysfunction had higher levels of circulating ACE compared to those with normal left ventricular function, while there was no association between ACE and central hemodynamics. ACE might play a role in the pathogenesis of left ventricular dysfunction and our findings suggest a direct effect on the heart rather than affecting central blood pressure.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2011. 73 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1224
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-67215 (URN)978-91-7393-243-1 (ISBN)
Public defence
2011-04-15, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2011-04-04 Created: 2011-04-04 Last updated: 2012-01-09Bibliographically approved
2. Influence of Genetics and Mechanical Properties on Large Arteries in Man
Open this publication in new window or tab >>Influence of Genetics and Mechanical Properties on Large Arteries in Man
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Arterial pathology is the major contributor to cardiovascular diseases and mortality. The mechanical properties of arteries are independent factors for cardiovascular disease and mortality, where genetics influence the structure of the arterial wall, which may result in change in arterial stiffness. The aims of this thesis were to study the mechanical properties of the popliteal artery (PA) in healthy subjects and the influence of angiotensin-converting enzyme (ACE) polymorphism and Fibrillin-1 (FBN1) polymorphism on large arteries. Further, the impact of FBN1 polymorphism on cardiovascular morbidity and mortality was investigated.

The PA is, after the abdominal aorta, the most common site of aneurysmal development. The PA was studied in healthy subject with ultrasound and the diameter increased and the distensibility decreased with age, with men having lower distensibility than women. This seems not to be the behavior of a true muscular artery but rather of a central elastic artery such as the aorta, and might have implications for the susceptibility to aneurysm formation, as well as the association of dilating disease between the PA and the aorta. The wall stress in the PA was low and unaffected by age, probably caused by a compensatory remodeling response with an increase in wall thickness. This indicates that other mechanisms than wall stress contribute to the process of pathological dilatation in the PA.

The ACE D allele may be associated with abdominal aortic aneurysm. Elderly men with the ACE D allele were associated with increased abdominal aortic stiffness compared to men carrying the I/I genotype. This suggests that the ACE D allele impairs arterial wall integrity, and in combination with local hemodynamic and other genetic factors it may have a roll in aneurysm formation.

The FBN1 2/3 genotype has been associated with increased systolic blood pressure. The FBN1 2/3 genotype in middle-aged men was associated with increased abdominal aortic stiffness and blood pressure which indicates an increased risk for developing cardiovascular disease. The increased presence of plaque in the carotid artery of middle-aged men with the FBN1 2/3 genotype indicates a pathological arterial wall remodeling with a more pronounced atherosclerotic burden, but did however not affect the risk of cardiovascular events and/or death in this population. This relationship needs to be studied further.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2013. 77 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1340
National Category
Physiology
Identifiers
urn:nbn:se:liu:diva-86144 (URN)978-91-7519-761-6 (ISBN)
Public defence
2013-01-25, Orginalet, Qulturum, Hus B4, , Länssjukhuset Ryhov, Jönköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2012-12-07 Created: 2012-12-07 Last updated: 2012-12-10Bibliographically approved

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Ljungberg, LizaDe Basso, RachelAlehagen, UrbanBjörck, HannaPersson, KarinDahlström, UlfLänne, Toste
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