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Circulating angiotensin-converting enzyme levels are associated with left ventricular dysfunction, but not with central aortic blood pressure, aortic augmentation or pulse pressure amplification
Linköping University, Department of Medicine and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medicine 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 Medicine and Health Sciences. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medicine and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
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2011 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Aim: This study aimed to explore the link between angiotensin-converting enzyme (ACE), and left ventricular (LV) function and central hemodynamics.

Methods and Results: The study population consisted of 672 subjects (322 men and 350 women) aged 69-87 years. LV function was evaluated semi-quantitatively by visual estimation using echocardiography. Central aortic blood pressure, aortic augmentation and pulse pressure amplification were determined in a sub-group of 422 subjects by the use of the SphygmoCor system. ACE genotype was determined by PCR and circulating ACE levels were analysed using enzyme-linked immunosorbent assay (ELISA).

LV dysfunction was associated with higher levels of circulating ACE compared to subjects with normal LV function (p=0.007). This association remained after adjustment for factors previously shown to affect circulating ACE (ACE-genotype, age, diabetes and smoking) (p=0.036). There was a significant association between ACE level and degree of LV dysfunction (p=0.019). However, there was no association of ACE genotype or circulating ACE with central aortic blood pressure, aortic augmentation or pulse pressure amplification.

Conclusion: Subjects with LV dysfunction have higher levels of circulating ACE compared to subjects with normal LV function. ACE might play a role in the pathogenesis of LV dysfunction and our data indicates a direct effect on the heart rather than affecting central blood pressure.

Place, publisher, year, edition, pages
2011.
Keyword [en]
ACE, Heart Failure, Polymorphism, Renin-Angiotensin System, Central hemodynamics
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-67214OAI: oai:DiVA.org:liu-67214DiVA: diva2:408326
Available from: 2011-04-04 Created: 2011-04-04 Last updated: 2017-03-27Bibliographically 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: 2017-03-27Bibliographically approved

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Ljungberg, LizaAlehagen, UrbanDe Basso, RachelPersson, KarinDahlström, UlfLänne, Toste

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Ljungberg, LizaAlehagen, UrbanDe Basso, RachelPersson, KarinDahlström, UlfLänne, Toste
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PharmacologyFaculty of Health SciencesCardiologyDepartment of Cardiology UHLDepartment of Medicine and Health SciencesPhysiologyDepartment of Thoracic and Vascular Surgery in Östergötland
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