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Adipocyte-derived l...
Adipocyte-derived leucine aminopeptidase genotype and response to antihypertensive therapy
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- Hallberg, Pär (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Klinisk farmakogenomik och osteoporos,Department of Medical Sciences, Uppsala University, Uppsala, Sweden
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- Lind, Lars (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Kardiovaskulär epidemiologi,Department of Medical Sciences, Uppsala University, Uppsala, Sweden; AstraZeneca Research & Development, Mölndal, Sweden
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- Michaëlsson, Karl, 1959- (author)
- Uppsala universitet,Ortopedi,Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
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- Kurland, Lisa, 1960- (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Department of Medical Sciences, Uppsala University, Uppsala, Sweden
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- Kahan, Thomas (author)
- Karolinska Institutet
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- Malmqvist, Karin (author)
- Karolinska Institutet
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- Öhman, Karl Peter (author)
- AstraZeneca Research & Development, Mölndal, Sweden; Department of Medicine and Care, Faculty of Health Sciences, Linköping, Sweden
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- Nyström, Fredrik, 1963- (author)
- Östergötlands Läns Landsting,Linköpings universitet,Hälsouniversitetet,Internmedicin,EMT-endo
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- Liljedahl, Ulrika (author)
- Uppsala universitet,Molekylär medicin,Department of Medical Sciences, Uppsala University, Uppsala, Sweden
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- Syvänen, Ann-Christine (author)
- Uppsala universitet,Molekylär medicin,Department of Medical Sciences, Uppsala University, Uppsala, Sweden
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- Melhus, Håkan (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Klinisk farmakogenomik och osteoporos,Department of Medical Sciences, Uppsala University, Uppsala, Sweden
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Malmqvist, X? (author)
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(creator_code:org_t)
- 2003-09-18
- 2003
- English.
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In: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261 .- 1471-2261. ; 18:3, s. 11-
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Abstract
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- BackgroundAdipocyte-derived leucine aminopeptidase (ALAP) is a recently identified member of the M1 family of zinc-metallopeptidases and is thought to play a role in blood pressure control through inactivation of angiotensin II and/or generation of bradykinin. The enzyme seems to be particularly abundant in the heart. Recently, the Arg528-encoding allele of the ALAP gene was shown to be associated with essential hypertension.MethodsWe evaluated the influence of this polymorphism on the change in left ventricular mass index in 90 patients with essential hypertension and echocardiographically diagnosed left ventricular hypertrophy, randomised in a double-blind study to receive treatment with either the angiotensin II type I receptor antagonist irbesartan or the beta1-adrenoceptor blocker atenolol for 48 weeks. Genyotyping was performed using minisequencing.ResultsAfter adjustment for potential covariates (blood pressure and left ventricular mass index at baseline, blood pressure change, age, sex, dose and added antihypertensive treatment), there was a marked difference between the Arg/Arg and Lys/Arg genotypes in patients treated with irbesartan; those with the Arg/Arg genotype responded on average with an almost two-fold greater regression of left ventricular mass index than patients with the Lys/Arg genotype (-30.1 g/m2 [3.6] vs -16.7 [4.5], p = 0.03).ConclusionsThe ALAP genotype seems to determine the degree of regression of left ventricular hypertrophy during antihypertensive treatment with the angiotensin II type I receptor antagonist irbesartan in patients with essential hypertension and left ventricular hypertrophy. This is the first report of a role for ALAP/aminopeptidases in left ventricular mass regulation, and suggests a new potential target for antihypertensive drugs.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Keyword
- Aminopeptidase
- irbesartan
- hypertension
- polymorphism
- left ventricular hypertrophy
- angiotensin
- pharmacogenomics
- bradykinin
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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Hallberg, Pär
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Lind, Lars
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Michaëlsson, Kar ...
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Kurland, Lisa, 1 ...
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Kahan, Thomas
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Malmqvist, Karin
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Öhman, Karl Pete ...
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Nyström, Fredrik ...
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Liljedahl, Ulrik ...
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Syvänen, Ann-Chr ...
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Melhus, Håkan
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Malmqvist, X?
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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- MEDICAL AND HEALTH SCIENCES
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BMC Cardiovascul ...
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Uppsala University
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Örebro University
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Karolinska Institutet
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Linköping University