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Biomedical subjects

V Hombach

Publications and source records attributed to V Hombach.

At least 19 recordsLinked to original sources
PubMed1998

Quantification of mitral and tricuspid regurgitation by the proximal flow convergence method using two-dimensional colour Doppler and colour Doppler M-mode: influence of the mechanism of regurgitation.

In patients with mitral (n=77: organic=49, functional=28) and tricuspid regurgitation (n=55: functional=54) quantified by angiography, the temporal variation of the proximal flow convergence region throughout systole was assessed by colour Doppler M-Mode, and peak and mean radius of the proximal isovelocity surface area for 28 cm/s blood flow velocity were measured. Additionally, the peak radius derived from two-dimensional colour Doppler was obtained. About 50% of the patients with mitral and tricuspid regurgitation showed a typical temporal variation of the flow convergence region related to the mechanism of regurgitation. The different proximal isovelocity surface area radii were similarly correlated to the angiographic grade in mitral and tricuspid regurgitation (rank correlation coefficients 0.55-0.89) and they differentiated mild to moderate (grade < or =II) from severe (grade > or =III) mitral and tricuspid regurgitation with comparable accuracy (82-96%). However, moderate mitral regurgitation due to leaflet prolapse in two patients was correctly classified by the mean M-mode radius and overestimated by both peak radii. Only half of the patients showed a typical variation of the flow convergence region related to the mechanism of regurgitation. The different proximal isovelocity surface area radii were suitable to quantify mitral and tricuspid regurgitation in most patients. However, in mitral regurgitation due to leaflet prolapse the use of the mean M-mode radius may avoid overestimation.

Adult↗
PubMed1998

Heart-rate variability for discrimination of different types of neuropathy in patients with insulin-dependent diabetes mellitus.

It has been shown that patients with insulin-dependent diabetes mellitus (IDDM) may reveal abnormal alterations in heart-rate variability (HRV) due to autonomic neuropathy. This study was performed to prove whether heart-rate variability can be used to stratify diabetic patients with different types of neuropathy. 48 patients with IDDM (age 17-64 yr) underwent standard function tests to assess autonomic and peripheral neuropathy. According to the results of these tests they were divided into 4 groups: Group 1: 18 patients without autonomic or peripheral neuropathy. Group 2: 13 patients with peripheral neuropathy. Group 3: 7 patients with autonomic neuropathy. Group 4: 9 patients with autonomic and peripheral neuropathy. HRV was measured by continuous 24-hours monitoring and time domain parameters were calculated. The results were compared with sex and age-matched healthy controls according to the individual characteristics of the groups and among each subgroup. Our results showed that in Group 1 there was a significant difference of time domain parameters indicative of parasympathetic influence, i.e. rMSSD and pNN50 in comparison to the control subjects (p = 0.002, p = 0.008). These results depended on the duration of diabetes; a subgroup of patients with a duration of IDDM of less than 2 years had no significant differences of HRV values. Group 2 showed the same significant differences. Group 3 and 4 showed significant differences in all measured time domain variables (SDNN, SDANN, SDNN index, rMSSD and pNN50) in comparison to the control subjects (p < 0.04). A comparison of group 1 with group 2 offered significant differences in rMSSD and pNN50 (p = 0.004, p = 0.003). Comparing group 1 with group 3 and 4, all HRV parameters showed significant differences (p < 0.03). In conclusion, HRV is able to distinguish between patients with different types of neuropathy depending on the involvement of parasympathetic or more sympathetic influenced parameters. Furthermore, this method is able to unmask early manifestations of neurological disorders prior to their detection by neurological function tests.

Adolescent↗
PubMed1998

A remark on the high-conductance calcium-activated potassium channel in human endothelial cells.

The patch-clamp technique was used to examine the presence of large conductance calcium-activated potassium channels (BKCa) in human endothelial cells and to characterize their properties in terms of voltage dependence, ion conduction and blockade by iberiotoxin (IbTX). Experiments were performed using cell-attached and outside-out configurations on human umbilical vein endothelial cells (HUVEC). For the experiments HUVECs, which were passaged 6-19 times, were used. In early passages channel activities were absent suggesting the appearance of BKCa depending on cell culture time. The inverse logarithmic voltage sensitivity was 10.17 mV (median) for cell-attached recordings and 12.10 mV (median) for outside-out patches (membrane voltage range: 60-120 mV, symmetrical 140 mM K+ solutions). The I/V relationship was quasilinear in the range of 0-80 mV and exhibited a nonlinear behaviour under further depolarization suggesting some kind of saturation mechanism. Using a sigmoid function to fit the data, channel conductance was calculated as 172.9 pS (median) for cell-attached patches and as 262.1 pS (median) for outside-out patches. IbTX, known as one of the most selective blockers of BKCa was perfused to outside-out patches. In two out of three experiments there was complete block of the ion channel after 1 min.

Cells, Cultured↗
PubMed1998

Time-dependent changes of heart rate variability after percutaneous transluminal angioplasty.

OBJECTIVES: It is not known whether the improvement of myocardial perfusion by percutaneous transluminal coronary angioplasty (PTCA) is followed by a response of the autonomic nervous system depending on the recovery of the myocardium. In this study we investigated changes of heart rate variability parameters in patients before and after PTCA at different time intervals. METHODS: In 42 patients with coronary artery disease documented on angiography, before and after PTCA 24-hour measurements of heart rate variability (HRV) were performed from Holter tapes. The time elapsed between the two measurements was 3 to 4 days in 26 patients and 6 to 8 months in 16 patients. Time domain parameters of HRV were calculated. RESULTS: Comparison of the two recordings showed that the parameters rMSSD, pNN50, and SDNN index decreased, whereas SDNN and SDANN increased. These changes were not statistically significant. A subgroup analysis revealed different results for patients with and without previous myocardial infarction: the parasympathetically and more sympathetically influenced parameters revealed different changes in these groups. Other variables such as ejection fraction or severity of coronary artery disease did not influence the HRV results. Although no statistically significant difference was seen on comparison of the patients with different recording intervals, patients with a longer interval between the two measurement periods showed higher values of all HRV parameters closer to normalized values. This observation may be explained by a delayed recovery of myocardial function after successful revascularization by PTCA.

Adult↗
PubMed1998

Comparison of the proximal flow convergence method and the jet area method for the assessment of the severity of tricuspid regurgitation.

AIMS: To compare the value of the proximal flow convergence method and the jet area method for the determination of the severity of tricuspid regurgitation. METHODS AND RESULTS: The proximal isovelocity surface area radius and the jet area/length were measured in 71 consecutive patients with angiographically graded (grade 0/I-III) tricuspid regurgitation. Rank correlation coefficients with the angiographic grade were 0.71 (P < 0.001) for the proximal isovelocity surface area radius (aliasing border of 28 cm.s-1), 0.66 (P < 0.001) for the jet area, and 0.63 (P < 0.001) for the jet length. The proximal isovelocity surface area radius was significantly correlated with the jet area/length (correlation coefficients 0.82/0.77, P < 0.001). Correct differentiation between mild to moderate (grade I-II) and severe (grade III) tricuspid regurgitation was achieved in 62 of 71 patients (87%) by means of the proximal isovelocity surface area radius, in 61 of 71 (86%) by the jet area, and in 62 of 71 (87%) by the jet length. Grade III tricuspid regurgitation was not identified in five of 21 patients (24%) by means of the proximal isovelocity surface area radius, in six of 21 (29%) by the jet area, and in seven of 21 (33%) by the jet length. CONCLUSION: The flow convergence method and the jet area method are of similar value for the determination of the severity of tricuspid regurgitation. Both methods differentiated mild to moderate from severe tricuspid regurgitation in most patients. However, underestimation of severe tricuspid regurgitation in 20-30% of the cases represents a serious limitation of both methods.

Adult↗
PubMed1998

Effect of diltiazem and verapamil on endothelin release by cultured human coronary smooth-muscle cells and endothelial cells.

Recent data suggest that endothelin (ET) production is enhanced in coronary atherosclerotic lesions. In several studies, an anti-atherosclerotic effect has been attributed to calcium-channel antagonists. This study aimed to investigate whether ET release from cultured human coronary artery smooth muscle and endothelial cells is influenced by the calcium-channel antagonists diltiazem and verapamil. Coronary plaque smooth-muscle cells (SMCs) were isolated from primary stenosis plaque material. Normal coronary smooth muscle and endothelial cells were obtained from organ donors. Addition of diltiazem (5, 15, 25, 50, or 100 micrograms/ml) and verapamil (0.25, 2.5, 25, 50, or 75 micrograms/ml) to the culture medium induced in all three cell types a dose-dependent reduction in ET secretion (coronary plaque SMCs: diltiazem 98.1 +/- 1.5, 94.9 +/- 5.0, 82.0 +/- 6.4**, 63.3 +/- 3.7***, 38.9 +/- 2.4***; control 108.4 +/- 2.8; verapamil 97.0 +/- 7.7, 91.9 +/- 5.5, 67.3 +/- 4.5**, 30.6 +/- 3.0***, 27.6 +/- 2.2***; control 103.4 +/- 6.1 pg/10(4) cells, n = 6; normal coronary SMCs: diltiazem 9.6 +/- 0.7, 8.7 +/- 0.6, 5.4 +/- 0.5***; 3.7 +/- 0.5***, 3.2 +/- 0.4***; control 10.7 +/- 0.5; verapamil 10.3 +/- 0.9, 10.0 +/- 0.7, 6.6 +/- 0.5***, 4.0 +/- 0.3***, 3.0 +/- 0.3***; control 11.1 +/- 0.6 pg/10(4) cells, n = 6; means +/- SEM, **p < 0.01, ***p < 0.001 vs. control). These data suggest that ET release from cultured coronary smooth muscle and endothelial cells is decreased by diltiazem and verapamil. In further studies, it remains to be elucidated whether the local application of diltiazem or verapamil might have a beneficial effect on the progression of coronary atherosclerosis.

Aged↗
PubMed1998

Expression of intercellular adhesion molecule-1 in human coronary endothelial and smooth muscle cells after stimulation with tumor necrosis factor-alpha.

BACKGROUND: The intercellular adhesion molecule-1 (ICAM-1) is one of several human cell adhesion molecules that play a critical role in the early stages of postangioplasty restenosis. In this study, the in-vitro expression of ICAM-1 in human coronary endothelial cells and human coronary smooth muscle cells (SMC) after stimulation with tumor necrosis factor-alpha (TNF-alpha) was investigated. METHODS AND RESULTS: SMC were isolated from the media of normal human coronary arteries (n = 26) up to 10 h post mortem (HCMSMC) and from human atherosclerotic coronary arteries (HCPSMC) that were extracted by thrombendarterectomy (n = 25). Endothelial cells of human coronary arteries (HCAEC) were purchased from Clonetics (Cell System, Remagen, Germany), and endothelial cells from human umbilical cord veins (HUVEC) were isolated after vaginal delivery. For investigations of the effect of TNF-alpha (2.5, 5, 10, and 20 ng/ml) on the proliferative activity of HUVEC, HCAEC, HCPSMC, and HCMSMC, serum-free media was used. After 24 h cell number and cell size distribution were measured in a cell analyzer system. The proliferation of HCPSMC and HCMSMC was increased by TNF-alpha; however, significant differences compared with controls were not reached. The proliferation of HUVEC and HCAEC was significantly reduced by TNF-alpha. For investigations of the effect of TNF-alpha (2.5, 5, 10, and 20 ng/ml) on the surface expression of ICAM-1, monoclonal anti-ICAM-1 antibodies (84H10) were used. The expression of ICAM-1 was analyzed using an immunofluorescence microscope. For flow cytometry analysis, 5 x 10(3) cells (100% gated) were analyzed using a fluorescence-activated cell sorter. In control cultures with no stimulation, the expression of ICAM-1 was positive in HCAEC, HCPSMC, HCMSMC, and HUVEC. TNF-alpha stimulated the expression of ICAM-1 in a time- and dose-dependent manner. After maximal stimulation with TNF-alpha (20 ng/ml for 24 h), the expression of ICAM-1 was stronger in HCMSMC than in HCPSMC. CONCLUSIONS: These results suggest that the cytokine TNF-alpha regulates the expression of ICAM-1 in both human coronary endothelial cells and SMC, and could therefore play an important role in the pathophysiology of inflammatory and immune processes in restenosis after angioplasty.

Cell Division↗
PubMed1998

C-reactive protein frequently colocalizes with the terminal complement complex in the intima of early atherosclerotic lesions of human coronary arteries.

There is increasing evidence that complement activation may play a role in atherogenesis. Complement proteins have been demonstrated to be present in early atherosclerotic lesions of animals and humans, and cholesterol-induced atherosclerotic lesion formation is reduced in complement-deficient animals. Potential complement activators in atherosclerotic lesions are now a subject matter of debate. C-reactive protein (CRP) is an acute-phase protein that is involved in inflammatory processes in numerous ways. It binds to lipoproteins and activates the complement system via the classic pathway. In this study we have investigated early atherosclerotic lesions of human coronary arteries by means of immunohistochemical staining. We demonstrate here that CRP deposits in the arterial wall in early atherosclerotic lesions with 2 predominant manifestations. First, there is a diffuse rather than a focal deposition in the deep fibroelastic layer and in the fibromuscular layer of the intima adjacent to the media. In this location, CRP frequently colocalizes with the terminal complement complex. Second, the majority of foam cells below the endothelium show positive staining for CRP. In this location, no colocalization with the terminal complement proteins can be observed. Our data suggest that CRP may promote atherosclerotic lesion formation by activating the complement system and being involved in foam cell formation.

Animals↗
PubMed1998

Direct enzyme immunometric measurement of plasma big endothelin-I concentrations and correlation with indicators of left ventricular function.

Recent studies have suggested that the plasma concentrations of endothelin-1, a potent vasoconstrictive peptide, are increased in patients with congestive heart failure. This study aimed to evaluate a new direct ELISA for big endothelin-1 (the precursor of endothelin-1), in comparison with a big endothelin-1 ELISA using plasma sample extraction, and to investigate whether plasma big endothelin-1 concentrations correlate with indicators of left ventricular function. The direct ELISA yielded significantly (P < 0.001) lower results than the assay with extracted samples (0.9 +/- 0.5 pmol/L vs 2.7 +/- 1.9 pmol/L; n = 90); however, the results of the two assays were closely correlated (r = 0.86, P < 0.001). Plasma big endothelin-1 concentrations exhibited a significant (P < 0.001) negative correlation (r = -0.46, r = -0.40) with the left ventricular ejection fraction and a significant positive correlation (r = 0.40, P < 0.001; r = 0.36, P < 0.01) with the left ventricular end-diastolic pressure and the left ventricular end-diastolic (r = 0.42, r = 0.38, P < 0.001) and end-systolic (r = 0.52, r = 0.47, P < 0.001) volume indices. Plasma big endothelin-1 concentrations were notably greater in patients with New York Heart Association (NYHA) class II-IV symptoms than in patients without cardiac disease or in patients categorized to NYHA class I. These data suggest that plasma big endothelin-1 concentrations, measured by a direct ELISA, correlate with hemodynamic indicators and symptoms of left ventricular dysfunction.

Adult↗
PubMed1998

[Clinical and economic cost-benefit relations in treatment of patients with coronary heart disease].

Economic evaluation of medical treatment in terms of costs and utility has gained increasing interest within the medical community and in political discussions. In particular this applies for highly prevalent diseases such as coronary artery disease, still the most common cause of death in the western world. Health economy studies can be performed from different perspectives (e.g., hospital, insurance company, society) and with various approaches (e.g., cost-utility analysis, cost minimization). Those will be discussed for the primary prevention of myocardial infarction, coronary stent implantation, and for rehabilitation programs after myocardial infarction, serving as examples. Health-economical analyses provide data to compare treatment strategies beyond a certain speciality. However, economic evaluation is only one step within the medical assessment process and does not per se imply the political allocation of financial resources.

Angioplasty, Balloon, Coronary↗
PubMed1997

Influence of physical activity on 24-hour measurements of heart rate variability in patients with coronary artery disease.

This study assessed the influence of physical activity on time domain variables of heart rate variability (HRV) during 24-hour electrocardiographic registrations. Changes in time domain variables of HRV (in particular SDNN) obtained from Holter recordings were proven as strong predictors of cardiac events in patients with coronary artery disease. Although 24-hour measurements of HRV recordings are a standard technique, little is known about the effects of the environment during the registration period. This applies especially to the type and nature of physical activity. In a prospective study, 106 patients with angiographically proven coronary artery disease were randomized into 2 groups. Group 1 consisted of 54 patients with recordings under normal daily physical activities. Group 2 consisted of 52 patients who were immobilized during the recording. Both groups were comparable concerning clinical parameters. The results of 24-hour measurements of HRV with analysis of time domain variables (SDNN, SDANN, SDNN index, rMSSD, and pNN50) were compared among the 2 patients groups, and with a healthy control group. Comparison of immobilized patients with healthy controls showed statistically significant differences of all HRV parameters (p <0.01). However, when comparing the activity group with healthy controls, none of the parameters showed any significant differences. Comparison of the subgroups revealed statistically significant differences of the parameters SDNN, SDANN (p <0.01), and borderline results for rMSSD and pNN50 (p = 0.05). Our results indicate that time domain variables of HRV calculated from 24-hour recordings are significantly influenced by the level of physical activity and the upright posture during registration. This methodologic aspect has to be considered, especially if HRV measurements are used as prognostic markers in patients with coronary heart disease.

Adult↗
PubMed1997

Signal-averaged electrocardiogram in patients with insulin-dependent (type 1) diabetes mellitus with and without diabetic neuropathy.

The purpose of this study was to investigate the presence of ventricular late potentials derived from signal-averaged ECG in patients with IDDM with and without diabetic neuropathy. Eighty patients with IDDM but without evidence of cardiac disease and 80 age-matched healthy control subjects were investigated. The corrected QT interval was measured from the standard surface electrocardiogram. Ventricular late potentials were derived from signal-averaged electrocardiogram. Out of the 80 diabetic patients, 20 had an autonomic neuropathy, 20 had an isolated peripheral neuropathy, and 40 had no symptoms of neuropathy. The corrected QT interval was significantly prolonged in patients with an autonomic neuropathy as compared with the control group (436 +/- 23 ms(x 5) vs 384 +/- 23 ms(x 5), p < 0.001). In the other patient groups there was no significant prolongation of the corrected QT interval. Ventricular late potentials were present in 3 diabetic patients with an isolated peripheral neuropathy and in 1 control subject (NS). No diabetic patient with an autonomic neuropathy had ventricular late potentials. Our data did not indicate an increased incidence of ventricular late potentials derived from signal-averaged electrocardiogram in diabetic patients independent of a coexisting diabetic neuropathy or a prolonged corrected QT interval.

Adolescent↗
PubMed1997

Ca(2+)-activated K+ channels in human smooth muscle cells of coronary atherosclerotic plaques and coronary media segments.

The behavior of Ca(2+)-activated K+ channels of large conductance (BKCa) in smooth muscle cells, which were obtained from atherosclerotic plaque material (SMCP) and from media segments (SMCM) of human coronary arteries, were compared using the patch-clamp technique. Voltage-clamp protocols in cell-attached patches revealed the characteristic voltage-dependent activation of BKCa in both cell groups. Single-channel conduction as 216.4 +/- 16.7 pS (n = 6) in SMCP and 199.9 +/- 6.7 pS (n = 6) in SMCM in symmetrical 140 mM K+ solutions. Using outside-out patches, external perfusion with 500 microM tetraethylammonium ions caused a typical "flickery block" of the unitary current. The selective BKCa channel inhibitor iberiotoxin (50 nM) effectively blocked BKCa, channel activity. Comparing BKCa open-state probabilities (P0) at +80 mV in cell-attached patches, a highly significant difference between SMCP (P0 = 0.1438 +/- 0.1301; n = 15) and SMCM (P0 = 0.0093 +/- 0.0044; n = 15; Kruskal-Wallis test, p < 0.001) was found. In contrast to this finding, there was no significant difference in the open-state probability of BKCa, between SMCP (P0 = 0.542 +/- 0.0237; n = 9) and SMCM (P0 = 0.0472 +/- 0.0218; n = 10; p = n.s.) using inside-out patches. The results show an interesting difference in the behavior of large conductance Ca(2+)-activated K+ channel in SMCP compared to SMCM with a significantly higher channel activity in human smooth muscle cells obtained from coronary atherosclerotic plaque material. This finding may indicate an important functional role of BKCa channels in the development of atherosclerosis.

Calcium↗
PubMed1997

Immunohistochemical colocalization of the terminal complex of human complement and smooth muscle cell alpha-actin in early atherosclerotic lesions.

There is substantial evidence that activated components of the complement cascade are present in atherosclerotic lesions, and it was suggested some years ago that smooth muscle cells may be an important target of complement attack by the terminal components of the cascade, C5b-9, also called the membrane attack complex. Recent in vitro studies have shown that assembly of membrane attack complex on smooth muscle cells leads to the release of monocyte chemotactic protein-1, and, if this were to occur in vivo, then it could be responsible for the recruitment of monocytes into the lesion. In this study we have investigated the localization of C5b-9 in early atherosclerotic lesions of human coronary arteries, collected from autopsies, by immunohistochemical staining, C5b-9 was found to colocalize widely with smooth muscle cell alpha-actin, but not with intact macrophages, thus supporting the hypothesis that interaction of complement with smooth muscle cells may indeed be important in atherogenesis.

Actins↗
PubMed1997

Seasonal variations of rheological and hemostatic parameters and acute-phase reactants in young, healthy subjects.

The incidence of cardiovascular diseases is increased in winter months. Recent studies have shown seasonal changes in plasma viscosity, fibrinogen, and factor VII activity with elevated levels during winter. An increase in these factors generates a "hypercoagulable state," which may lead to a rise in cardiovascular morbidity and mortality. It has been suggested that an increase in upper respiratory infections might be the underlying cause for the raised acute-phase reactants, in particular fibrinogen, during the winter season. We investigated seasonal variations of 26 parameters, determining blood rheology and hemostasis in 16 healthy volunteers (8 men and 8 women) aged 20 to 41 years. They were seen at monthly intervals over a period of 1 year. Seasonal variation with peak fitted values in the winter months was found for plasma viscosity (P < .001 for the seasonal difference), red blood cell deformability (P < .001), whole blood viscosity (P < .001), hemoglobin (P < .001), hematocrit (P < .001), mean corpuscular volume (P = .001), platelet count (P = .01), alpha 1-glycoprotein (P < .001), fibrinogen (measured by immunonephelometry; P < .001), plasminogen activator inhibitor-1 (P = .002), LDL cholesterol (P = .003), and triglyceride levels (P < .001). HDL cholesterol (P < .001) and cortisol (P = .001) showed inverse seasonal patterns, with a maximum during summertime. No statistically significant seasonal variations were seen for red blood cell aggregation, complement factor C4, total cholesterol, ceruloplasmin, haptoglobin, white blood cell count, and plasminogen. These data do not support the hypothesis that increased morbidity and mortality from cardiovascular diseases during winter may be mainly attributable to increased synthesis of acute-phase proteins due to infections. The cause for the seasonal variations in rheological and hemostatic parameters remains unclear and should be studied in more detail.

Acute-Phase Proteins↗
PubMed1996

Functional upregulation of the vascular endothelial growth factor receptor KDR by hypoxia.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a specific endothelial mitogen and chemoattractant that has been shown to be useful for inducing therapeutic angiogenesis in ischemic myocardium and found to stimulate mitogenicity and chemotaxis of endothelial cells through the receptor tyrosine kinase KDR. Although VEGF expression is upregulated by hypoxic stimuli, regulation of KDR remained unknown under these conditions. METHODS AND RESULTS: With the use of human umbilical vein endothelial cells and transfected porcine aortic endothelial cells, KDR protein was found to be upregulated under hypoxic conditions (2% O2) in both cell types. This process of KDR upregulation was found to be reversible, was maximal after 24 hours of hypoxia, and was regulated on a posttranscriptional level. Furthermore, the susceptibility for VEGF-induced mitogenicity was enhanced under hypoxic conditions as shown by [3H]-thymidine incorporation assay. The activated state of increased VEGF function in hypoxic endothelial cells was associated with elevated tyrosine phosphorylation of KDR as demonstrated by anti-phosphotyrosine blot. CONCLUSIONS: These data indicate that hypoxia stimulates VEGF-dependent signaling not only by upregulation of VEGF ligand but also by functional upregulation of a specific signaling receptor. Therefore, these data provide evidence that the endothelium plays an active role in hypoxia-induced angiogenesis.

Animals↗
PubMed1996

Different effects of estrogen and progesterone on experimental atherosclerosis in female versus male rabbits. Quantification of cellular proliferation by bromodeoxyuridine.

BACKGROUND: The aim of the present study was to compare the effect of estrogen and progesterone on the development of experimental atherosclerosis in female versus male rabbits to assess possible sex-specific differences. METHODS AND RESULTS: A total of 32 female and 32 male New Zealand White rabbits were ovariectomized or castrated. In addition to a 0.5% cholesterol diet, the rabbits received estradiol alone (1 mg/kg body wt [BW] per week), progesterone alone (25 mg/kg BW per week), or combined estradiol-progesterone in these dosages during 12 weeks. Ovariectomized female and castrated male rabbits served as control groups without hormone treatment. Before excision of the vessels, bromodeoxyuridine labeling was performed to determine the extent of cellular proliferation in the atherosclerotic lesions. The aortic arch was analyzed immunohistologically and morphometrically. An inhibitory effect of estrogen on intimal plaque size was found in female rabbits compared with the ovariectomized control group (0.7 +/- 0.5 versus 3.7 +/- 2.5 mm2, P < .002; proliferating cells, 3.1 +/- 1.8% versus 8.5 +/- 2.6%, P < .002). In combination with progesterone, however, estrogen was not able to reduce intimal plaque size or cellular proliferation. In contrast, estradiol in castrated male rabbits was not associated with an inhibitory effect on cellular proliferation or intimal thickening compared with controls (estrogen treatment, 7.6 +/- 2.1% proliferating cells and 2.8 +/- 1.0 mm2 neointima; control group, 7.2 +/- 2.1% cellular proliferation and 2.9 +/- 1.2 mm2 intimal thickening). CONCLUSIONS: Our data suggest that the atheroprotective effect of estrogen is probably due to a mechanism that is present in female rabbits only.

17-alpha-Hydroxyprogesterone↗