Assessment of the aortic tunica media histological changes in relation with the cause of death.

AIM: The authors set out to evaluate the correlations between three of the main morphological aortic parameters (elastic fibers - FE, collagen fibers - FCOL, and smooth muscle fibers - FM) and the cause of death. MATERIALS AND METHODS: Study groups included 25 cases died of a vascular disease (V_P), 37 cases died of a non-vascular disease (NV_P) and 28 cases died of a violent/suspect non-pathological cause of death (V_Dth), the latter group representing also the control group. Four aortic cross-sections (base, arch, thoracic, and abdominal regions) were collected during autopsy from the selected cases, fixed in 10% buffered formalin and first of all photographed together with a calibrating ruler. Then, they were embedded in paraffin, sectioned off at 4 µm and stained with Hematoxylin-Eosin (HE) and Orcein. The obtained histological slides were transformed into virtual slides. Fibrillary components amounts were using a custom-made software, developed in MATLAB (MathWorks, USA). Statistical tools used were Pearson's correlation test, t-test (two-sample assuming equal variances) and one-way analysis of variance (ANOVA) test. RESULTS AND DISCUSSIONS: The amounts of the three fibrillary components of the aortic tunica media had a synchronous variation in all aortic regions in each of the three groups, excepting FCOL in the group of patients died from vascular pathology, which presented only a trend of synchronous variation along the aorta. FE had their lowest values and FCOL had their highest values in patients died from vascular pathology. FCOL had always higher levels than FE in people died from any pathological condition, vascular or non-vascular. FM had always at least two times lower level than that of the other types of fibers, regardless of whether the person died due to a pathological condition or not. CONCLUSIONS: The different pathological conditions causing death are influencing the fibrillary composition of aortic tunica media. Further studies are required to reveal other changes in the morphology of aortic wall in particular and vascular wall in general that could be related with different pathological conditions affecting the entire organism.

Assessment of a pro-healing stent in an animal model of early neoatherosclerosis.

BACKGROUND: Neoatherosclerosis represents an accelerated manifestation of atherosclerosis in nascent neointima after stenting, associated with adverse events. We investigated whether improved reendothelialization using RGD-coated stents results in diminished vascular permeability and reduced foam cell formation compared to standard DES in atherosclerotic rabbits. METHODS AND RESULTS: Neointimal foam cell formation was induced in rabbits (n = 7). Enhanced endothelial integrity in RGD-coated stents resulted in decreased vascular permeability relative to DES, which was further confirmed by SEM and TEM. Cell culture experiments examined the effect of everolimus on endothelial integrity. Increasing concentrations of everolimus resulted in a dose-dependent decrease of endothelial cell junctions and foam cell transformation of monocytes, confirming the relevance of endothelial integrity in preventing permeability of LDL. CONCLUSION: Incomplete endothelial integrity was confirmed as a key factor of neointimal foam cell formation following stent implantation. Pro-healing stent coatings may facilitate reendothelialization and reduce the risk of neoatherosclerosis.

[Assessment of the intima and media of carotid arteries in the course of hypertension in the elderly]. / Ocena kompleksu blony wewnetrznej i srodkowej tetnic szyjnych w przebiegu nadcisnienia tetniczego u osób w podeszlym wieku.

According to the position of the European Society of Hypertension in 2009, the thickening of the inner and middle membrane complex of the carotid arteries (I-M CCA), or the finding of atherosclerotic plaques is associated with high cardiovascular risk. The increase in I-M CCA thickness, assessed within the carotid artery, is considered the initial stage of atherosclerosis. According to the concept of parallel development of atherosclerosis in many arterial areas I-M CCA is a recognized marker of the process involving other arteries, such as coronary arteries, kidney or lower limbs. AIM: The aim of the study was evaluation of the intima and media of carotid arteries - I-M in the course of hypertension in the elderly. MATERIALS AND METHODS: The study involved 63 women and 17 men, aged from 75 to 93 years, who were diagnosed with arterial hypertension in accordance with the guidelines of the Polish Society of Hypertension. Patients were divided into two groups. The first pair consisted of a group of 1 hypertensive patients (HA) lasting up to 10 years of age over 85 years and a group of 2 patients with HA lasting up to 10 years at the age of 75-85 years. The second pair is group I - patients with HA over 10 years of age over 85 years and group II - patients with HA lasting over 10 years at the age of 75-85. Carotid artery examination was performed using the Aloka SSD-1100 ultrasound machine. The measurements were made within the left and right carotid wall of the common carotid artery in the anterior and lateral-posterior projection. The maximum thickness of the inner and middle membranes was measured in three places within two segments of the common carotid artery. RESULTS: It was observed that in the group of patients treated longer due to hypertension, the thickness of the intima-media complex is significantly higher than in patients with shorter duration. Moreover, in the examined group of patients in the analysis of individual correlations, life expectancy was influenced, among others, by significantly on the thickness of I-M CCA. CONCLUSIONS: Both the older age of patients and the longer duration of hypertension caused thickening of the intima-media complex. The duration of hypertension greater than 10 years had a greater impact on the thickness of this complex than the age of the patients.

Assessment of apoptotic cells in the wall of thrombophlebitic saphenous vein.

INTRODUCTION: Programmed cell death plays a critical role in various physiological processes. In the present study, we investigated its possible pathogenic role in primary varicose veins. We studied histological changes in surgical specimens from thrombophlebitic saphenous veins. In thrombophlebitic saphenous, varicose, and healthy veins, we also determined the number of apoptotic cells, and investigated apoptosis in the role of the pathogenesis of varicose veins. METHODS: Forty-four specimens of thrombophlebitic saphenous veins and simple varicose veins were collected. Thirteen samples of normal great saphenous veins were also collected (control group). Apoptosis of venous walls was determined by terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) and immunofluorescence methods. The corpuscular number per high-power field was counted under light microscopy. RESULTS: A significantly higher apoptotic ratio of the intima and media were observed in control veins as compared with thrombophlebitic saphenous veins and simple varicose veins (p < 0.01). A significant difference was not observed between thrombophlebitic saphenous veins and simple varicose veins (p > 0.05). A significant difference was not seen between the intima and media of the three groups (p > 0.05). CONCLUSION: In the walls of thrombophlebitic saphenous veins and varicose veins, the apoptotic indices were clearly decreased. The results suggest that the process of programmed cell death was inhibited in walls of thrombophlebitic saphenous veins and varicose veins.

Primary sclerosing cholangitis: detailed histologic assessment and integration using bioinformatics highlights arterial fibrointimal hyperplasia as a novel feature.

OBJECTIVES: Liver biopsy diagnosis of primary sclerosing cholangitis (PSC) is difficult. We performed a detailed histologic analysis of PSC cases using novel bioinformatics analysis to identify histologic features that may be useful in its diagnosis. METHODS: PSC liver explants were examined and compared with primary biliary cirrhosis and hepatitis C explants to act as controls. Demographic, macroscopic, and histologic variables were analyzed using both conventional statistics and an integrative bioinformatics approach, significance analysis of microarrays (SAM), and hierarchical clustering analysis (HCA). RESULTS: The PSC group was younger and had distinctive PSC features, including bile duct scars, onion-skin fibrosis, and arterial fibrointimal hyperplasia. SAM allowed the integration of variables by comparing PSC and control groups, whereas HCA was able to correctly categorize each group. CONCLUSIONS: This study demonstrates characteristic PSC histology as well as arterial hyperplasia to be distinctive features that may aid in PSC diagnosis and be confirmed by bioinformatics.

The influence of vascular anatomy on carotid artery stenting: a parametric study for damage assessment.

Carotid artery stenting is emerging as an alternative technique to surgery for the treatment of symptomatic severe carotid stenosis. Clinical and experimental evidence demonstrates that both plaque morphology and biomechanical changes due to the device implantation can be possible causes of an unsuccessful treatment. In order to gain further insights of the endovascular intervention, a virtual environment based on structural finite element simulations was built to emulate the stenting procedure on generalized atherosclerotic carotid geometries which included a damage model to quantify the injury of the vessel. Five possible lesion scenarios were simulated by changing both material properties and vascular geometrical features to cover both presumed vulnerable and stable plaques. The results were analyzed with respect to lumen gain and wall stresses which are potentially related to the failure of the procedure according to previous studies. Our findings show that an elliptic lumen shape and a thinner fibrous cap with an underlying lipid pool result in higher stenosis reduction, while large calcifications and fibrotic tissue are more prone to recoil. The shielding effect of a thicker fibrous cap helps to reduce local compressive stresses in the soft plaque. The presence of a soft plaque reduces the damage in the healthy vascular structures. Contrarily, the presence of hard plaque promotes less damage volume in the fibrous cap and reduces stress peaks in this region, but they seem to increase stresses in the media-intima layer. Finally the reliability of the achieved results was put into clinical perspective.

[Prognostic assessment for formation of a group of cardiovascular high risk among personnel participating in atomic submarines utilization].

Ultrasound scanning of main vessels (common carotid, internal carotid, common and superficial femoral, posterior tibial arteries) in staffers of shipyard "Nerpa"--branch of JSC "Shipbuilding center Zvezdochka" (Snezhnogorsk city Murmansk region)--engaged into atomic submarines utilization. Findings are atherosclerotic changes in common carotid and common femoral arteries--increased thickness of intima-media complex over the reference values or atherosclerotic plaque formation. The changes were maximal in a group of males aged over 50 with length of service over 25 years. Discriminant analysis helped to suggest a mathematic model to forecast cardiovascular diseases in personnel of "Nerpa" shipyard.

Long-term health benefits and costs of measurement of carotid intima-media thickness in prevention of coronary heart disease.

OBJECTIVE: Recently, it was demonstrated that information on carotid intima-media thickness (CIMT) and plaque may improve coronary heart disease (CHD) risk prediction through reclassification of some individuals to the correct risk category using the Framingham risk score. Our objective was to assess the currently unknown cost-effectiveness of CIMT measurements in primary prevention. METHODS: A hypothetical cohort of men and women aged 50-59 years and at intermediate or high CHD risk based on data from the Atherosclerosis Risk in Communities Study was simulated using a Markov model. Myocardial infarction (MI) events were used as a proxy for CHD. The effectiveness of pharmaceutical treatment was varied in the analysis. Sensitivity analysis was performed to obtain robust results. RESULTS: CIMT-based reclassification induced a 1% lower absolute risk of MI and 0.01-0.02 increase in quality-adjusted life years (QALYs) for men, and a 1-3% lower risk, and 0.03-0.05 increase in QALYs for women, over a period of 20-30 years. Corresponding costs were an additional $100 per man, and a cost-saving of $200-300 per woman. Over a 10-year period CIMT measurements were cost-effective with a probability of 66% (men), and 94% (women). Over a 30-year period, CIMT measurements had acceptable cost-effectiveness for men and women. CONCLUSION: Performing CIMT measurements in asymptomatic men and women aged 50-59 years results in additional, but small, health benefits. It takes time for these health benefits to outweigh the initial CIMT measurement costs. Our results support CIMT measurements for cardiovascular risk stratification, in particular for women, when focusing on long-term health.

Cardiorespiratory fitness and carotid artery intima media thickness in men with type 2 diabetes.

BACKGROUND: We tested the hypothesis that higher levels of cardiorespiratory fitness are inversely associated with carotid artery intima media thickness in 746 (age 53 ± 7 yrs) men with type 2 diabetes. METHODS: We measured common carotid intima media thickness and defined carotid atherosclerosis as a carotid intima media thickness > 1.0 mm. Cardiorespiratory fitness was directly measured by peak oxygen uptake using expired gases analysis during a standard treadmill test. RESULTS: Cardiorespiratory fitness was independently associated with common carotid intima media thickness in multivariable regression (ß = -0.15, P < .05). After adjusting for established risk factors, high and moderate cardiorespiratory fitness were associated with lower odds ratios for having carotid atherosclerosis--0.49 (95% CI, 0.30-0.81), and 0.59 (95% CI, 0.38-0.92), respectively--as compared with low cardiorespiratory fitness. Each 1 metabolic equivalent increment higher cardiorespiratory fitness was associated with 27% (OR = 0.73; 95% CI, 0.61-0.87) lower prevalence of carotid atherosclerosis. CONCLUSIONS: These results suggest that high cardiorespiratory fitness is inversely associated with common carotid intima media thickness in men with type 2 diabetes.

Ex vivo assessment of vascular response to coronary stents by optical frequency domain imaging.

OBJECTIVES: This study sought to examine the capability of optical frequency domain imaging (OFDI) to characterize various morphological and histological responses to stents implanted in human coronary arteries. BACKGROUND: A precise assessment of vascular responses to stents may help stratify the risk of future adverse events in patients who have been treated with coronary stents. METHODS: Fourteen human stented coronary segments with implant duration ≥ 1 month from 10 hearts acquired at autopsy were interrogated ex vivo by OFDI and intravascular ultrasound (IVUS). Comparison with histology was assessed in 134 pairs of images where the endpoints were to investigate: 1) accuracy of morphological measurements; 2) detection of uncovered struts; and 3) characterization of neointima. RESULTS: Although both OFDI and IVUS provided a good correlation of neointimal area with histology, the correlation of minimum neointimal thickness was inferior in IVUS (R(2) = 0.39) as compared with OFDI (R(2) = 0.67). Similarly, IVUS showed a weak correlation of the ratio of uncovered to total stent struts per section (RUTSS) (R(2) = 0.24), whereas OFDI maintained superiority (R(2) = 0.66). In a more detailed analysis by OFDI, identification of individual uncovered struts demonstrated a sensitivity of 77.9% and specificity of 96.4%. Other important morphological features such as fibrin accumulation, excessive inflammation (hypersensitivity), and in-stent atherosclerosis were characterized by OFDI; however, the similarly dark appearance of these tissues did not allow for direct visual discrimination. The quantitative analysis of OFDI signal reflections from various in-stent tissues demonstrated distinct features of organized thrombus and accumulation of foamy macrophages. CONCLUSIONS: The results of the present study reinforce the potential of OFDI to detect vascular responses that may be important for the understanding of long-term stent performance, and indicate the capability of this technology to serve as a diagnostic indicator of clinical success.

Imaging assessment of cardiovascular risk in asymptomatic adults.

OBJECTIVE: This article will address the role of coronary artery calcium (CAC) and carotid intima-media thickness screening in asymptomatic at-risk adults and the broader concept of vulnerable plaque as it applies to this population. CONCLUSION: Imaging for assessment of cardiovascular risk in asymptomatic adults has been the subject of considerable interest and some controversy. The incorporation of CAC and carotid intima-media thickness assessment into recent guidelines reflects the growing evidence base for these applications.

Assessment of vascular phenotype using a novel very-high-resolution ultrasound technique in adolescents after aortic coarctation repair and/or stent implantation: relationship to central haemodynamics and left ventricular mass.

OBJECTIVES: Coarctation of the aorta (CoA) has been associated with abnormal vascular function, increased blood pressure (BP) and premature cardiovascular disease even after a successful intervention. The objective was to determine the severity of residual cardiovascular abnormalities in youths after CoA repair and their relation to regional BP. DESIGN: Cross-sectional study in tertiary healthcare setting. METHODS: Thirty-six youths with CoA (age 16±1 years; neonatal surgery only: n=16; surgery and/or stent implantation: n=20) and 37 age-matched controls were prospectively examined using a very-high-resolution vascular ultrasound imaging, echocardiography and applanation tonometry. RESULTS: CoA was associated with increased right arm systolic BP (p<0.001), intima-media thickness (IMT) in the common carotid (p<0.001), right brachial (p<0.05) and radial (p<0.05) arteries and ascending aortic stiffness (p<0.05). Carotid IMT correlated positively with age at first intervention (r=0.36, p<0.05). With left subclavian flap-type repair, left-arm systolic BP (p<0.001) and left brachial (p<0.001), radial (p<0.001) and ulnar (p<0.05) arterial IMTs were all reduced. When adjusted for BP, body mass index, age and gender, only carotid IMT (p<0.001) and left ventricular mass (p=0.013) of stented patients, as well as left-arm arterial IMTs (p<0.01) in subclavian flap-type repair patients, remained different from the controls. The significant associations of the stented patients disappeared after the adjustment for later patient age at intervention (median 8.7 vs 0.03 years, p<0.001). Residual arm-leg BP gradients correlated positively with carotid and brachial IMT. No differences between the CoA patients and the controls were found for arterial adventitial thicknesses, lumen dimensions, thigh systolic BP, abdominal aorta and carotid stiffness and right carotid to radial pulse wave velocity. CONCLUSION: CoA repair in early childhood is associated with increased preductal arterial IMT, left ventricular mass and ascending aortic stiffness in adolescents. The more pronounced cardiovascular abnormalities after CoA stent implantation are likely related to older patient age at the time of intervention.

Two-dimensional speckle-tracking strain imaging in the assessment of mechanical properties of carotid arteries: feasibility and comparison with conventional markers of subclinical atherosclerosis.

AIMS: The aim of our study was to assess the two-dimensional carotid strain as an index of arterial stiffness in a population of patients without carotid atherosclerotic plaques. METHODS AND RESULTS: Two-dimensional carotid strain, carotid intima-media thickness (CIMT), stiffness index (ß), Peterson's elastic modulus, and distensibility coefficient were evaluated in 47 patients. For all patients, cardiovascular risk scores were calculated. Peak systolic circumferential strain was significantly correlated with conventional indices of arterial stiffness and with the CIMT. Peak systolic circumferential strain adjusted for pulse pressure was the only parameter that showed a significant difference between the three cardiovascular risk groups in which patients were classified. Two-dimensional carotid strain showed an excellent reproducibility. CONCLUSION: The two-dimensional strain allows the assessment of carotid arterial mechanics. Probably the assessment of arterial stiffness allows a better risk stratification of patients.

Noninvasive assessment of atherosclerosis in apolipoprotein-e knockout mice by ultrasound biomicroscopy.

Intima media thickness is a marker for human atherosclerosis. This study aimed to validate the hypothesis that atherosclerosis progression in vivo in mice can be visualized noninvasively using high-resolution ultrasound biomicroscopy (UBM), and to study the association between UBM characteristics and plasma lipids in the apolipoprotein-E knockout (ApoE-/-) mouse model. Four age groups of male ApoE-/- mice were used as atherosclerotic models, with age-matched male C57BL/6 mice used as controls. Plaque thickness and area measured by UBM correlated with histologic measurements (r = 0.81, r = 0.70, respectively; p < 0.001). Serum total cholesterol, low density lipoprotein cholesterol and triglycerides were higher in the ApoE-/- groups compared with controls (p < 0.01). Plaque thickness was correlated with total cholesterol (r = 0.505, p < 0.001). High-resolution UBM provides a noninvasive, accurate means of detecting atherosclerosis progression in vivo in mice and can detect changes in the early stage of atherosclerosis.

Risk stratification based on metabolic syndrome as well as non- metabolic risk factors in the assessment of carotid atherosclerosis.

AIM: We aimed to develop a new approach to risk stratification using metabolic syndrome as well as traditional non-metabolic risk factors, and to examine its validity in carotid atherosclerosis. METHODS: A total of 1,189 men and women aged 21-93 years old were stratified according to the absence or presence of metabolic syndrome defined by Japanese criteria, non-metabolic risk factors, and a past history of coronary heart disease. The risk stratification was as follows: (S-1) persons without a past history, non-metabolic risk factors and metabolic syndrome, (S-2a) those with metabolic syndrome only, (S-2b) those with non-metabolic risk factors only, (S-3) those with non-metabolic risk factors and metabolic syndrome but no past history, and (S-4) those with a past history. Carotid atherosclerosis was defined as maximum intima-media thickness ≥1.1 mm of the far wall of the common carotid artery. RESULTS: Compared with individuals without these three risk components (S-1), the odds ratio was 7.2 (2.8-18.6) for a past history (S-4), 4.3 (1.7-10.9) for non-metabolic risk factors plus metabolic syndrome but no past history (S-3), 2.6 (1.1-6.4) for non-metabolic risk factors only (S-2b) and 0.5 (0.0-5.7) for metabolic syndrome only (S-2a). Net reclassification improvement from metabolic syndrome only (presence versus absence) to our risk stratification (≥S-3 versus < S-3) was 16.4% (p< 0.0001), suggesting that our risk stratification improved the classification of atherosclerosis in comparison to metabolic syndrome only. CONCLUSION: Risk stratification based on traditional non-metabolic risk factors plus metabolic syndrome rather than metabolic syndrome only appears to be more useful for the clinical assessment of atherosclerosis, and probably in the prevention and control of atherosclerotic disease.

Assessment of atherosclerotic plaque burden with an elastin-specific magnetic resonance contrast agent.

Atherosclerosis and its consequences remain the main cause of mortality in industrialized and developing nations. Plaque burden and progression have been shown to be independent predictors for future cardiac events by intravascular ultrasound. Routine prospective imaging is hampered by the invasive nature of intravascular ultrasound. A noninvasive technique would therefore be more suitable for screening of atherosclerosis in large populations. Here we introduce an elastin-specific magnetic resonance contrast agent (ESMA) for noninvasive quantification of plaque burden in a mouse model of atherosclerosis. The strong signal provided by ESMA allows for imaging with high spatial resolution, resulting in accurate assessment of plaque burden. Additionally, plaque characterization by quantifying intraplaque elastin content using signal intensity measurements is possible. Changes in elastin content and the high abundance of elastin during plaque development, in combination with the imaging properties of ESMA, provide potential for noninvasive assessment of plaque burden by molecular magnetic resonance imaging (MRI).

Assessment by optical coherence tomography of stent struts across side branch. -Comparison of bare-metal stents and drug-elution stents.-.

BACKGROUND: Late stent thrombosis (LST) after drug-eluting stent (DES) implantation is a major clinical problem that has not been fully explained. Incomplete neointimal coverage of stent struts is an important morphometric predictor of LST, which may be associated with impaired healing and the absence of full coverage of struts at branch-point ostia. Optical coherence tomography (OCT) was performed to compare 3 types of stents placed across side branches. METHODS AND RESULTS: At 9-month follow-up, the neointimal coverage of the struts of 58 stents across a side branch was measured by OCT (bare metal (BMS), n = 20; sirolimus-eluting (SES), n = 23; paclitaxel-eluting (PES), n = 15). According to the diameter ratio of side branch to main vessel, the side branches were classified as either large (ratio > 0.33) or small (ratio ≤ 0.33). BMS had the lowest frequency of uncovered struts (29.4%) and the greatest neointimal thickness on the struts (123 ± 33 µm). Neointimal thickness on the struts was less for SES than for PES (72 ± 16 vs. 91 ± 22 µm, P = 0.009), but there was no difference in the frequency of uncovered struts (66.1% vs. 58.6%, P=0.493). For large side branches, the frequency of uncovered struts was greater than in the small group for SES (87.5% vs. 40.7%, P = 0.0002) and PES (83.3% vs. 18.2%; P = 0.0013); there was no significant difference for BMS (43.8% vs. 16.7%, P = 0.138). CONCLUSIONS: Neointimal coverage on struts across a side branch was less frequently observed in DES than in BMS, particularly in large side branches.

The assessment of carotid intima media thickness and serum paraoxonase-1 activity in Helicobacter pylori positive subjects.

BACKGROUND: The role of inflammation in the pathogenesis and progression of atherosclerosis has been increasingly discussed. Although the seroepidemiological studies have suggested a relationship between Helicobacter pylori (H. pylori) infection and atherosclerosis; the issue is still controversial. It is well known that abnormal lipid profil is related to atherosclerosis and the measurement of carotid-intima media thickness (CIMT) is one of the surrogate marker of atherosclerosis. The serum concentration of high-density lipoprotein (HDL-C) has been known to have an inverse correlation with the development of atherosclerosis. Paraoxonase-1 (PON1) is a major anti-atherosclerotic component of HDL-C. PON1 activity is related to lipid peroxidation and prospective cardiovascular risk. The aim of this study was to investigate CIMT and serum PON1 activities along with lipid parameters in H. pylori positive and negative subjects. METHODS: Thirty H. pylori positive subjects and thirty-one negative subjects were enrolled. H. pylori infection was diagnosed by the presence of positivity of stool H. pylori antigen test or Carbon 14 labeled urea breath test. Serum PON1 activity was measured spectrophotometrically. Traditional cardiovascular risk factors were investigated and laboratory analysis included measurement of serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein cholesterol (LDL-C). We assessed CIMT by high-resolution ultrasound of both common carotid arteries. RESULTS: We found that the mean and maximum values of right and overall CIMT in H. pylori positive subjects were significantly thicker than those of H. pylori negative subjects. There was no significant differences in serum HDL-C, LDL-C, TC levels and TC/HDL-C ratios between two groups. Serum TG levels of H. pylori positive subjects were significantly higher than those of H. pylori negative subjects (p = 0.014). We found that PON1 activities were significantly lower in H. pylori positive subjects compared with negative subjects. No significantly correlation was observed between PON1 and CIMT values. CONCLUSIONS: There is an increase in CIMT values in patients with H. pylori positive compared to H. pylori negative subjects. PON1 activity decrease significantly in H. pylori positive subjects. However, an association between PON1 and CIMT was not found. These data indicated that H. pylori may have a role in atherosclerotic processes, however, further studies are needed to evaluate the exact mechanisms.

Lead contributes to arterial intimal hyperplasia through nuclear factor erythroid 2-related factor-mediated endothelial interleukin 8 synthesis and subsequent invasion of smooth muscle cells.

OBJECTIVE: To validate the hypothesis that the toxic heavy metal lead (Pb) may be linked to cardiovascular diseases via the initiation of atherosclerosis, in vivo and in vitro studies were conducted. METHODS AND RESULTS: During the human study part of this project, serum Pb levels of healthy young women were correlated to carotid intima-media thickness. Multivariate logistic regression analyses showed that increased serum Pb levels were significantly associated with an increased intima-media thickness (P=0.01; odds ratio per SD unit, 1.6 [95% CI, 1.1 to 2.4]). In vitro, Pb induced an increase in interleukin 8 production and secretion by vascular endothelial cells. Nuclear factor erythroid 2-related factor-2 is the crucial transcription factor involved in Pb-induced upregulation of interleukin 8. Endothelial cell-secreted interleukin 8 triggered intimal invasion of smooth muscle cells and enhanced intimal thickening in an arterial organ culture model. This phenomenon was further enhanced by Pb-increased elastin synthesis of smooth muscle cells. CONCLUSIONS: Our data support the hypothesis that Pb is a novel, independent, and significant risk factor for intimal hyperplasia.