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  • 1.
    Björck, Hanna M.
    et al.
    Linköping University.
    Eriksson, Per
    Karolinska Institutet.
    Alehagen, Urban
    Linköping University.
    De Basso, Rachel
    Linköping University.
    Ljungberg, Liza U.
    Linköping University.
    Persson, Karin
    Linköping University.
    Dahlstrom, Ulf
    Linköping University.
    Länne, Toste
    Linköping University.
    Gender-Specific Association of the Plasminogen Activator Inhibitor-1 4G/5G Polymorphism With Central Arterial Blood Pressure2011In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 24, no 7, p. 802-808Article in journal (Refereed)
    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.

  • 2.
    De Basso, Rachel
    Linköpings universitet, Fysiologi.
    Influence of genetics and mechanical properties on large arteries in man2013Doctoral 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.

  • 3.
    De Basso, Rachel
    et al.
    Jönköping Hospital.
    Hedblad, Bo
    Lund University.
    Carlson, Joyce
    Lund University.
    Persson, Margaretha
    Lund University.
    Östling, Gerd
    Lund University.
    Länne, Toste
    Linköping University.
    Increased carotid plaque burden in men with the fibrillin-1 2/3 genotype2014In: Clinical and experimental pharmacology & physiology, ISSN 0305-1870, E-ISSN 1440-1681, Vol. 41, no 9, p. 637-642Article in journal (Refereed)
    Abstract [en]

    Fibrillin-1 (FBN1) is an important constituent of the vascular wall and earlier studies have indicated an effect of the FBN1 2/3 genotype on blood pressure as well as aortic stiffness in men. The aim of the present study was to determine whether the FBN1 2/3 genotype was associated with the presence of carotid plaque and incident cardiovascular morbidity and mortality in middle-aged subjects. The FBN1 genotype was characterized in 5765 subjects (2424 men, 3341 women; age 45-69years) recruited from the Malmo Diet and Cancer Study Cardiovascular Cohort, Sweden. Plaque occurrence and intima-media thickness (IMT) of the carotid artery were assessed by ultrasound. The incidence of first cardiovascular events (myocardial infarction and stroke) and cause-specific mortality were monitored over a mean follow-up period of 13.2years. The most common FBN1 genotypes were 2/2, 2/3 and 2/4, which accounted for 92.2% (n=5317) of subjects. There were no differences between the three genotypes regarding age, blood pressure, glucose, lipids, smoking habits, common carotid artery diameter and intima-media thickness in men and women. The presence of plaque in the carotid artery was higher in men with the 2/3 genotype compared with the 2/2 and 2/4 genotypes (55% vs 46% and 50%, respectively; P=0.007). No similar differences were observed in women. No significant relationship was observed between FBN1 genotypes and the incidence of cardiovascular disease or all-cause mortality. The increased prevalence of plaque in the carotid artery of middle-aged men with the FBN1 2/3 genotype indicates pathological arterial wall remodelling with a more pronounced atherosclerotic burden.

  • 4.
    De Basso, Rachel
    et al.
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine.
    Sandgren, Thomas
    Capio Lundby Hosp, Gothenburg, Sweden.
    Ahlgren, Åsa Ryden
    Lund University.
    Länne, Toste
    Linköping University.
    Increased cardiovascular risk without generalized arterial dilating diathesis in persons who do not have abdominal aortic aneurysm but who are first-degree relatives of abdominal aortic aneurysm patients2015In: Clinical and experimental pharmacology & physiology, ISSN 0305-1870, E-ISSN 1440-1681, Vol. 42, no 6, p. 576-581Article in journal (Refereed)
    Abstract [en]

    There is a strong genetic predisposition towards abdominal aortic aneurysm (AAA), but it is unknown whether persons without AAA but with first-degree relatives who are AAA patients have a generalized dilating diathesis, defect arterial wall mechanics, or increased cardiovascular risk. The aim of the study was to investigate arterial diameters and wall mechanics at multiple arterial sites in these subjects and compare them with controls without a family history of AAA. This study included 118 first-degree relatives of patients with AAA and 66 controls (age: 40-80years). The abdominal aorta, common carotid artery, common femoral artery, and popliteal artery were investigated by echo-tracking ultrasound. The relatives had no arterial dilatation, but they did tend to have smaller diameters than controls. Relatives had a higher heart rate, diastolic blood pressure, and mean arterial pressure than controls. The distensibility coefficient and the compliance coefficient were decreased in all arteries in male relatives, adjusted for age and smoking; these coefficients were normalized after adjustment for mean arterial pressure and heart rate. Female relatives had a lower compliance coefficient in the abdominal aorta, adjusted for age and smoking. After adjustment for mean arterial pressure and heart rate, the difference disappeared. No general arterial dilatation in relatives without AAA was found, supporting the hypothesis that the dilating diathesis is linked to the aneurysmal manifestation in the abdominal aorta. Although the threat of aneurysmal dilatation and rupture seems to be lacking in these subjects, heart rate, blood pressure, and arterial wall stiffness were all increased, which may indicate a higher risk of developing cardiovascular morbidity and mortality.

  • 5.
    De Basso, Rachel
    et al.
    Jönköping Hospital.
    Åstrand, Håkan
    Jönköping Hospital.
    Ahlgren, Åsa Rydén
    Lund University.
    Sandgren, Thomas
    Capio Lundby Hospital, Gothenburg, Sweden.
    Länne, Toste
    Linköping University.
    Low wall stress in the popliteal artery: Other mechanisms responsible for the predilection of aneurysmal dilatation?2014In: Vascular Medicine, ISSN 1358-863X, E-ISSN 1477-0377, Vol. 19, no 2, p. 131-136Article in journal (Refereed)
    Abstract [en]

    The popliteal artery (PA) is, after aorta, the most common site for aneurysm formation. Why the PA is more susceptible than other peripheral muscular arteries is unknown. We hypothesized that the wall composition, which in turn affects wall properties, as well as the circumferential wall stress (WS) imposed on the arterial wall, might differ compared to other muscular arteries. The aim was to study the WS of the PA in healthy subjects with the adjacent, muscular, common femoral artery (CFA) as a comparison. Ninety-four healthy subjects were included in this study (45 males, aged 10-78 years and 49 females, aged 10-83 years). The diameter and intima-media thickness (IMT) in the PA and CFA were investigated with ultrasound. Together with blood pressure the WS was defined according to the law of Laplace adjusted for IMT. The diameter increased with age in both PA and CFA (p<0.001), with males having a larger diameter than females (p<0.001). IMT increased with age in both PA and CFA (p<0.001), with higher IMT values in males only in PA (p<0.001). The calculated WS was unchanged with age in both arteries, but lower in PA than in CFA in both sexes (p<0.001). In conclusion, this study shows that the PA and CFA WS is maintained during aging, probably due to a compensatory remodelling response with an increase in arterial wall thickness. However, the stress imposed on the PA wall is quite low, indicating that mechanisms other than WS contribute to the process of pathological arterial dilatation in the PA.

  • 6.
    Debasso, Rachel
    et al.
    Department of Medicine and Care, University of Linköping, Sweden; Department of Clinical Physiology, Jönköping Hospital, Länssjukhuset Ryhov, Jönköping, Sweden.
    Åstrand, H.
    Department of Medicine and Care, University of Linköping, Sweden.
    Bjarnegård, N.
    Department of Medicine and Care, University of Linköping, Sweden.
    Ahlgren, Å. R.
    Department of Clinical Physiology, Malmö University Hospital, Sweden.
    Sandgren, T.
    Department of Surgery, Helsingborg Hospital, Sweden.
    Länne, T.
    Department of Medicine and Care, University of Linköping, Sweden.
    The popliteal artery, an unusual muscular artery with wall properties similar to the aorta: Implications for susceptibility to aneurysm formation?2004In: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809, Vol. 39, no 4, p. 836-842Article in journal (Refereed)
    Abstract [en]

    Objective: The popliteal artery is, after the aorta, the most common site for aneurysm formation. Why the popliteal artery is more susceptible than other peripheral muscular arteries is unknown. An important factor may be differences in arterial wall composition as compared with other peripheral muscular arteries, which in turn affect wall properties. These are however unknown. We studied the mechanical wall properties of the popliteal artery in healthy subjects.

    Material and Methods: An ultrasound echo-tracking system was used to measure pulsatile changes in popliteal diameter in 108 healthy subjects (56 female, 52 male; age range, 9-82 years). In combination with blood pressure, stiffness (0), strain, cross-sectional artery wall compliance coefficient (CC), and distensibility coefficient (DC) were calculated. Intima-media thickness (IMT) was registered with a Philips P700 ultrasound scanner.

    Results: The popliteal diameter increased with age, and was larger in male subjects than in female subjects (P < .001). Fractional diameter change (strain) decreased with age (P < .001), and strain values were lower in male subjects than in female subjects (P < .01). Accordingly, stiffness increased with age (P < .001), with higher stiffness values in male subjects (P < .01). DC decreased with age (P < .001), with lower DC values in male subjects (P < .01). CC decreased with age, with no difference between genders (P < .001). IMT increased with age (P < .001), with higher IMT values in male subjects (P < .001). The increase in IMT did not affect distensibility.

    Conclusion: The wall properties of the popliteal artery are affected by age and gender, not only with an increase in diameter, but also with an age-related decrease in distensibility, with male subjects having lower distensibility than in female subjects. This seems not to be the behavior of a true muscular artery, but of a central elastic artery, such as the aorta, and might have implications for susceptibility to arterial dilatation, as well as the association of aneurysm formation between the aorta and the popliteal artery.

    Clinical Relevance: The popliteal artery is, after the abdominal aorta, the most common location for aneurysm formation in the arterial system. Why it is more susceptible than other arteries is unknown. This study shows that the wall function of the popliteal artery differs from other peripheral arteries, and instead show striking similarities to the abdominal aorta, indicating that the functional arrangement of arterial wall components are similar in the two arteries. This may have implications for the susceptibility to aneurysm formation, as well as the association of dilating disease between the popliteal artery and the abdominal aorta.

  • 7.
    Ljungberg, L. U.
    et al.
    Linköping University.
    De Basso, Rachel
    Linköping University.
    Alehagen, U.
    Linköping University.
    Björck, H. M.
    Linköping University.
    Persson, K.
    Linköping University.
    Dahlström, U.
    Linköping University.
    Länne, T.
    Linköping University.
    Impaired Abdominal aortic wall Integrity in Elderly Men Carrying the Angiotensin-converting Enzyme D Allele2011In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 42, no 3, p. 309-316Article in journal (Refereed)
    Abstract [en]

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

    Material: A total of 212 men and 194 women, aged 70-88 years, were studied. Methods: Mechanical properties of the abdominal aorta were determined using the Wall Track System, ACE genotype using the polymerase chain reaction (PCR) and circulating ACE level by enzyme-linked immunosorbent assay (ELISA).

    Results: In men, pulsatile diameter change differed between genotypes (II 0.70, ID 0.55 and DD 0.60 mm, P = 0.048), whereas a tendency was seen for distensibility coefficient (DC) (II 10.38, ID 7.68 and ID 8.79, P = 0.058). Using a dominant model (II vs. ID/DD), men carrying the ACE D allele had lower pulsatile diameter change (P = 0.014) and DC (P = 0.017) than II carriers. Multiple regression analyses showed additional associations between the D allele and increased stiffness beta, and reduced compliance coefficient.

    Conclusion: Men carrying the ACE D allele have stiffer abdominal aortas compared with II carriers. Deranged abdominal aortic stiffness indicates impaired vessel wall integrity, which, along with other local predisposing factors, may be important in aneurysmal disease. (C) 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  • 8.
    Ljungberg, Liza
    et al.
    Linköping University.
    Alehagen, Urban
    Linköping University.
    Länne, Toste
    Linköping University.
    Björck, Hanna
    Linköping University.
    De Basso, Rachel
    Linköping University.
    Dahlström, Ulf
    Linköping University.
    Persson, Karin
    Linköping University.
    The association between circulating angiotensin-converting enzyme and cardiovascular risk in the elderly: a cross-sectional study2011In: jraas. Journal of the renin-angiotensin-aldosterone system, ISSN 1470-3203, E-ISSN 1752-8976, Vol. 12, no 3, p. 281-289Article in journal (Refereed)
    Abstract [en]

    Introduction: A polymorphism in the angiotensin-converting enzyme gene (ACE I/D polymorphism) has been associated with increased risk for cardiovascular disease (CVD). This polymorphism affects the level of circulating ACE, but there is great individual variation, even between those with the same genotype. Few previous studies have investigated the link between circulating ACE and cardiovascular risk. The aim of this study was to investigate this association, and to examine the relationship between ACE level, ACE genotype and CVD.

    Materials and methods: The study population consisted of 322 men and 350 women aged 69-87. Plasma ACE level was determined using enzyme-linked immunosorbent assay (ELISA), and ACE genotype was analysed using PCR followed by gel electrophoresis.

    Results: In men, ACE levels increased with increasing number of cardiovascular risk factors (p = 0.003). There was a significant association in men between increased ACE level and both diabetes (p = 0.007) and smoking (p = 0.037).

    Conclusions: This study shows that cardiovascular risk factors (such as smoking and diabetes) are associated with higher levels of circulating ACE in men. High ACE levels may represent one of the cellular mechanisms involved in producing the vascular damage associated with cardiovascular risk factors.

  • 9.
    Ljungberg, Liza U.
    et al.
    Linköping University.
    Alehagen, Urban
    Linköping University.
    De Basso, Rachel
    Linköping University.
    Persson, Karin
    Linköping University.
    Dahlström, Ulf
    Linköping University.
    Länne, Toste
    Linköping University.
    Circulating angiotensin-converting enzyme is associated with left ventricular dysfunction, but not with central aortic hemodynamics2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 166, no 2, p. 540-541Article in journal (Other academic)
  • 10.
    Länne, T.
    et al.
    Division of Clinical Physiology, Department of Medicine and Care, University Hospital, Linköping, Sweden.
    De Basso, Rachel
    Division of Clinical Physiology, Department of Medicine and Care, University Hospital, Linköping, Sweden.
    Powell, J. T.
    University Hospitals of Coventry and Warwickshire, Walsgrave, Coventry, United Kingdom.
    Influence of fibrillin-1 genotype on aortic stiffness in men: a note of caution - Reply2006In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 100, no 4, p. 1431-1432Article in journal (Other academic)
  • 11.
    Powell, J. T.
    et al.
    University Hospitals of Coventry and Warwickshire, Walsgrave, Coventry, United Kingdom.
    Turner, R. J.
    University Hospitals of Coventry and Warwickshire, Walsgrave, Coventry, United Kingdom.
    Sian, M.
    University Hospitals of Coventry and Warwickshire, Walsgrave, Coventry, United Kingdom.
    Debasso, Rachel
    Division of Clinical Physiology, Department of Medicine and Care, University Hospital, Linköping, Sweden.
    Lanne, T.
    Division of Clinical Physiology, Department of Medicine and Care, University Hospital, Linköping, Sweden.
    Influence of fibrillin-1 genotype on the aortic stiffness in men2005In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 99, no 3, p. 1036-1040Article in journal (Refereed)
    Abstract [en]

    Aortic stiffness is a, predictor of cardiovascular mortality. The mechanical properties of the arterial wall depend on the connective tissue framework, with variation in fibrillin-1 and collagen I genes being associated with aortic stiffness and/or pulse pressure elevation. The aim of this study was to investigate whether variation in fibrillin-1 genotype was associated with aortic stiffness in men. The mechanical properties 4 the abdominal aorta of 79 healthy pen (range 28-81 yr) were investigated by ultrasonographic phase-locked echo tracking. Fibrillin-1 genotype, characterized by the variable tandem repeat in intron 28, and collagen type I alpha I genotype characterized by the 2,064 G>T polymorphism, were deterimined by using DNA from peripheral blood cells. Three common fibrillin-1 genotypes, 2-2, 2-3, and 2-4, were observed in 50 (64%), 10 (13%), and 11 (14%) of the men, respectively. Those of 2-3 genotype had higher pressure strain elastic modulus and aortic stiffness compared with men of 2-2 or 2-4 genotype (P = 0.005). Pulse pressure also was increased in the 2-3 genotype (P = 0.04). There was no significant association between type I collagen genotype and aortic stiffness in this cohort. In conclusion, the fibrillin-1 2-3 genotype in men was associated with increased aortic stiffness and pulse pressure, indicative of an increased risk for cardiovascular disease.

  • 12.
    Wanhainen, Anders
    et al.
    Uppsala University, Sweden.
    Mani, Kevin
    Uppsala University, Sweden.
    Vorkapic, Emina
    Linköping University, Sweden.
    De Basso, Rachel
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. ADULT. Division of Medical Diagnostics, Department of Clinical Physiology, Region Jönköping County, Sweden.
    Björck, Martin
    Uppsala University.
    Länne, Toste
    Linköping University.
    Wågsäter, Dick
    Linköping University.
    Screening of circulating microRNA biomarkers for prevalence of abdominal aortic aneurysm and aneurysm growth2017In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 256, p. 82-88Article in journal (Refereed)
    Abstract [en]

    Background and aims

    MicroRNA (miR) are important regulators of gene expression and biological processes and have recently been suggested as possible biomarkers for abdominal aortic aneurysm (AAA) disease. The aim of the present study was to assess the role of miR as biomarkers for initiation and progression of AAA disease, through evaluation of a wide range of miRs in a large population-based cohort, with AAA patients with linked clinical data regarding risk factors, AAA size and growth, as well as controls.

    Methods

    The expression of the 172 most commonly expressed miRs in plasma was analyzed by real-time PCR in samples from 169 screening-detected AAA patients and 48 age-matched controls.

    Results

    For 103 miRs, there was a significant difference in expression between AAA and controls. Of these, 20 miRs were differently expressed between fast and slow growing aneurysms. These miRs target genes known to be involved in AAA disease as well as novel genes and pathways. By combining the top altered miRs together with clinical variables, strong predictive values, determining growth of AAA, were obtained (area under curve = 0.86, p < 0.001).

    Conclusions

    This large cohort study identified several novel miRs with altered expression in AAA patients when compared to controls. Assessment of miR expression may offer an opportunity to predict disease progression and aneurysm growth.

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