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Gender-Specific Association of the Plasminogen Activator Inhibitor-1 4G/5G Polymorphism With Central Arterial Blood Pressure
Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences.
Karolinska Institute, Stockholm.
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: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 24, no 7, 802-808 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND The functional plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism has previously been associated with hypertension. In recent years, central blood pressure, rather than brachial has been argued a better measure of cardiovascular damage and clinical outcome. The aim of this study was to investigate the possible influence of the 4G/5G polymorphism on central arterial blood pressure in a cohort of elderly individuals. METHODS We studied 410 individuals, 216 men and 194 women, aged 70-88. Central pressures and pulse waveforms were calculated from the radial artery pressure waveform by the use of the SphygmoCor system and a generalized transfer function. Brachial pressure was recorded using oscillometric technique (Dinamap, Critikon, Tampa, FL). PAI-1 antigen was determined in plasma. RESULTS The results showed that central pressures were higher in women carrying the PAI-1 4G/4G genotype compared to female carriers of the 5G/5G genotype, (P = 0.025, P = 0.002, and P = 0.002 for central systolic-, diastolic-, and mean arterial pressure, respectively). The association remained after adjustment for potentially confounding factors related to hypertension. No association of the PAI-1 genotype with blood pressure was found in men. Multiple regression analysis revealed an association between PAI-1 genotype and plasma PAI-1 levels (P = 0.048). CONCLUSIONS Our findings show a gender-specific association of the PAI-1 4G/5G polymorphism with central arterial blood pressure. The genotype effect was independent of other risk factors related to hypertension, suggesting that impaired fibrinolytic potential may play an important role in the development of central hypertension in women.

Place, publisher, year, edition, pages
Nature Publishing Group , 2011. Vol. 24, no 7, 802-808 p.
Keyword [en]
aorta; arterial stiffness; blood pressure; genetics; hypertension; pressure pulse wave
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-69831DOI: 10.1038/ajh.2011.63ISI: 000291901100014OAI: oai:DiVA.org:liu-69831DiVA: diva2:433470
Note
Original Publication: Hanna Björck, Per Eriksson, Urban Alehagen, Rachel Debasso, Liza Ljungberg, Karin Persson, Ulf Dahlström and Toste Länne, Gender-Specific Association of the Plasminogen Activator Inhibitor-1 4G/5G Polymorphism With Central Arterial Blood Pressure, 2011, American Journal of Hypertension, (24), 7, 802-808. http://dx.doi.org/10.1038/ajh.2011.63 Copyright: Nature Publishing Group http://npg.nature.com/ Available from: 2011-08-10 Created: 2011-08-08 Last updated: 2017-12-08Bibliographically approved
In thesis
1. Vessel wall integrity: influence of genetics and flow
Open this publication in new window or tab >>Vessel wall integrity: influence of genetics and flow
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cardiovascular disease (CVD) is the major cause of death worldwide. Underlying causes, such as atherosclerosis and hypertension, are associated with remodeling of the vessel wall ultimately leading to loss of structural integrity. There are a number of factors that can influence vascular remodeling and hence structural integrity. The overall aim of this thesis was to investigate aortic wall integrity in relation to genetics and blood flow.

The influence of SNPs within the currently most robust susceptibility locus identified for CVD (chromosome 9p21.3) on abdominal aortic integrity was studied in elderly individuals. In men, risk-variants were associated with a decreased abdominal aortic stiffness, independent of other factors related to arterial stiffness. Impaired mechanical properties of the abdominal aortic wall may explain the association between chromosome 9p21.3 and vascular disease.

Plasminogen activator inhibitor 1 (PAI-1) is the key inhibitor of fibrinolysis, and involved in several processes associated with vascular remodeling. We investigated the impact of the PAI-1 4G/5G polymorphism on central aortic blood pressure as this pressure more strongly relates to cardiovascular morbidity and mortality than the peripheral pressure. Elderly women carrying the 4G/4G genotype had higher central aortic blood pressure than women carrying the 5G/5G genotype. The association was regardless of other risk factors related to hypertension, suggesting that an impaired fibrinolytic potential may play an important role in the development of hypertension in women.

Blood flow is a strong determinant of arterial growth and vascular function. We investigated flow-dependent gene expression and vessel wall morphology in the rat aorta under physiological conditions. Microarray analysis revealed a strong differential gene expression between disturbed and uniform flow pattern regions, particularly associated with transcriptional regulation. Moreover, several genes related to Ca2+ signalling were among the most highly differentially expressed. Up-regulation of Ca2+-related genes may be due to endothelial response to disturbed flow and assembly of cilia, consequently leading to functional and structural modifications of the vessel wall.

Bicuspid aortic valve (BAV) is a congenital disorder associated with disturbed ascending aortic blood flow. Using a new strategy to dissect flow-mediated gene expression we identified several novel flow-associated genes, particularly related to angiogenesis, wound healing and mechanosensing, showing differential expression in the ascending aorta between BAV and tricuspid aortic valve patients. Fifty-five percent of the identified genes were confirmed to be flowresponsive in the rat aorta. A disturbed flow, and consequently an altered gene expression, may contribute to the increased aneurysm susceptibility associated with BAV morphology.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2012. 84 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1270
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-73958 (URN)9789173930338 (ISBN)
Public defence
2012-01-20, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 09:15 (Swedish)
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Available from: 2012-01-17 Created: 2012-01-17 Last updated: 2017-12-12Bibliographically approved

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Björck, HannaAlehagen, UrbanDebasso, RachelLjungberg, LizaPersson, KarinDahlström, UlfLänne, Toste
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