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Biomedical subjects

Thomas Thulin

Publications and source records attributed to Thomas Thulin.

5 recordsLinked to original sources

Antibodies of IgM subclass to phosphorylcholine and oxidized LDL are protective factors for atherosclerosis in patients with hypertension.

OBJECTIVE: To determine the importance of antibodies against phosphorylcholine (PC) and oxidized low density lipoprotein (OxLDL) for development of atherosclerosis. METHODS AND RESULTS: Two hundred and twenty six individuals with established hypertension (diastolic pressure > 95mmHg) were from European Lacidipine Study on Atherosclerosis. Antibodies of IgG and IgM subclass were tested by ELISA against PC (aPC), cupper-oxidized (ox)- or malondialdehyde (MDA)-modified LDL. High-sensitivity C-reactive protein was measured by nephelometry. As a surrogate measure of atherosclerosis, we used the mean of the maximum intima-media thicknesses (IMT) in the far walls of common carotids and bifurcations was determined by ultrasonography at the time of enrolment, and 4 years following enrolment. aPC could be competed out by PC and OxLDL, while cardiolipin (CL) and beta2-glycoprotein I (beta2GPI) were less effective and phosphatidylserine (PS) not at all. Increases in IMT at follow-up were less common in subjects which at the time of enrolment had high IgM aPC (both 75th and 90th; odds ratios: 0.46; CI: 0.25-0.85; 0.36; CI: 0.15-0.87) and high IgM aOxLDL and aMDA-LDL (90th; odds ratios 0.27; p = 0.01; CI: 0.11-0.69 and 0.27; p = 0.01; CI: 0.11-0.69). CRP was unrelated to IMT-changes. The relationship between IgM aPC, aOxLDL and aMDA-LDL and changes in IMT was independent of age, treatment with atenolol or lacidipine, smoking and lipids. Women had higher levels of IgM antibodies tested (p < 0.05). CONCLUSIONS: High levels of IgM-antibodies against PC and OxLDL predict a favourable outcome in the development of carotid atherosclerosis in hypertensive subjects. Whether these antibodies could be used therapeutically deserves further study.

Cardiolipins↗

Serum heat shock protein 70 levels predict the development of atherosclerosis in subjects with established hypertension.

Although heat shock proteins (Hsp's) are present in the sera of healthy individuals and at elevated levels in subjects with early cardiovascular disease, their physiologic role in and value for predicting the development and/or progression of atherosclerosis have not been evaluated. Serum was obtained from 218 subjects with established hypertension (diastolic pressure >95 mm Hg) before their enrollment in the European Lacidipine Study on Atherosclerosis. Hsp60 and Hsp70, and anti-human Hsp60, anti-human Hsp70, and anti-mycobacterial Hsp65 antibody levels were measured by enzyme immunoassay. As an indicator of the presence/progression of atherosclerosis, the means of the maximum intima-media (I-M) thicknesses in the far walls of common carotid arteries and bifurcations (CBMmax) were determined by ultrasonography at the time of enrollment and 4 years afterward. Increases in I-M thicknesses at follow-up were less prevalent in subjects having high serum Hsp70 levels (75th percentile) at the time of enrollment (odds ratio, 0.42; 95% confidence interval [CI], 0.22 to 0.8, P=0.008). Although a similar trend was observed for serum Hsp60 levels, this was not statistically significant (odds ratio, 0.6; 95% CI, 0.32 to 1.11, P=0.10). There was no relation between anti-Hsp antibody levels and changes in I-M thicknesses. The relation between Hsp70 levels and changes in I-M thickness was independent of age, atenolol or lacidipine treatment, smoking habits, and blood lipid levels. These findings indicate that circulating Hsp70 levels predict the development of atherosclerosis in subjects with established hypertension, and an intriguing possibility is that Hsp70 protects against or modifies the progression of atherosclerosis in this subject group.

Arteriosclerosis↗

Circulating oxidized low-density lipoprotein is increased in hypertension.

Oxidized low-density lipoprotein (OxLDL) and autoantibodies to OxLDL (aOxLDL) are implicated in the development of atherosclerosis. The objective of this study was to determine the importance of these factors in hypertension, a major risk factor for atherosclerosis. Samples were obtained from 111 men with established hypertension (diastolic pressure >95 mmHg) from the Swedish component of an ongoing hypertension study (European Lacidipine study on Atherosclerosis, ELSA) and from 75 normotensive control men, who were from a Swedish population-screening programme (diastolic pressure <80 mmHg). The presence of carotid atherosclerosis and the intima-media thicknesses were determined by ultrasonography. A monoclonal antibody to OxLDL, EO6, was used to determine oxidation epitopes in LDL. aOxLDL of IgG and IgM subclass were tested by ELISA against OxLDL. Hypertensive men had increased OxLDL levels compared with normotensives ( P =0.002), whereas autoantibodies tested were largely similar between groups. There was no association between the antibodies tested, or OxLDL and carotid atherosclerosis. Age was not associated with OxLDL or aOxLDL measurements. Taken together, our findings indicate that OxLDL is elevated in hypertensive men, which may predispose to atherosclerosis in hypertension. In contrast, aOxLDL levels were unchanged and the role of aOxLDL may depend on disease stage and/or type.

Age Factors↗

Circulating heat shock protein and heat shock protein antibody levels in established hypertension.

OBJECTIVE: Serum Hsp60 and anti-Hsp65 antibody levels are raised in subjects with borderline hypertension, and there is an association between circulating Hsp60 levels and early atherosclerosis. Given the recognized relationship between hypertension and atherosclerosis, this study determined heat shock protein and heat shock protein antibody levels in subjects with established hypertension. METHODS: Samples from 111 men with hypertension were obtained from the European Lacidipine study on Atherosclerosis and samples from 75 normotensive controls were taken from a population-screening programme (diastolic pressure, 95 and 80 mmHg, respectively). Hsp60, Hsp70 and anti-human Hsp60, anti-human Hsp70 and anti-mycobacterial Hsp65 antibody levels were measured by enzyme immunoassay. Intima-media thickness (I-M) and the presence of carotid atherosclerosis were determined by ultrasonography. RESULTS: Hsp60, Hsp70 and anti-Hsp60 antibody levels in hypertension were similar to those in normotensive controls, whereas anti-Hsp70 and anti-Hsp65 antibody levels were elevated ( 0.001). Hsp60 levels and atherosclerosis were not associated. Anti-Hsp70 and anti-Hsp65 antibody levels were both associated with hypertension, independently of age, smoking habits and blood lipids. CONCLUSIONS: This study demonstrates elevated levels of selected heat shock protein antibodies in subjects with hypertension. Although the association between heat shock protein antibody levels and human cardiovascular stress/disease appears to be robust, the relationship of the latter with heat shock protein levels is more complex. Further studies are required before the factors inducing, and the clinical significance of, circulating heat shock proteins can be evaluated.

Antibodies↗