Arterial Wall In Patients Research Articles

PP.21.03

Objective: To evaluate the influence of fixed combination of perindopril and amlodipine on conductive and collagen-forming function of arterial wall in patients with arterial hypertension and COPD. Design and method: 60 patients with AH and CAD complicated with CHF, and accompanied with COPD were randomized into 2 equal groups for different antihypertensive treatment. Patients in the 1st group received fixed combination of perindopril and amlodipine (the dose titrated depending on baseline blood pressure). Patients in the 2nd group received enalapril or non-fixed combination of enelapril and amlodipine. Duration of therapy consisted of 6 months. Average age was 55,28 ± 7,81 years. Average AH grade was 2,32 ± 0,87. To evaluate vascular remodelling volume sphygmography was performed with VaSera VS-1000 device (Fucuda, Japan) determining right and left branch-ankle pulse wave velocity (R-PWV, L-PWV), cardio-ankle vascular index (CAVI1), carotid-femoral pulse wave velocity (PWV), PWV in aorta (aPWV) and carotid (cPWV), R-AI and C-AI augmentation indices. Type-1 tissue inhibitor of matrix metalloproteinases (TIMP-1), a common marker of arterial collagen matrix status was evaluated. Results: There was no worsening of COPD course during treatment. Also, there were no significant differences between the groups in goal BP achievement. In 2nd group BP < 110/70 mm Hg registered more often than in 1st one (p = 0.036). During therapy, both R-PWV and L-PWV in 1st group decreased significantly more, than in 2nd: 11,3 ± 3,4 and 16,6 ± 7,2% vs 2,7 ± 0,3 and 1,8 ± 0,5% (p < 0,001 and p < 0,001 respectively). CAVI1 in 1st group decreased more, than in 2nd: 1,8 ± 0,5% and 0,8 ± 0,2% (p = 0,003). PWV in aorta and C-PWV in 1st group decreased significantly more, than in 2nd: (p < 0,001 and p < 0,001 respectively). PWVcf decreased in 1st group on 19,5 ± 1,8, in 2nd one on 11,8 ± 2,19%, (p = 0,005). R-AI significantly decreased in 1st group, than in 2nd: 1,6 ± 0,5% vs 0,4 ± 0,1% (p < 0,001). TIMP1 significantly decreased in 1st group, than in 2nd (p < 0,001). Conclusions: Fixed combination of perindopril and amlodipine in AH and COPD patients provides more evident vasoprotective effect than non-fixed combinations of enalapril and amlodipine because of its physiological evaluation on diurnal BP profile without hypothensia. Both perindopril and amlodipine do not worse COPD course.

The contribution of HIV infection to intracranial arterial remodeling: A pilot study

Pathological arterial wall changes have been cited as potential mechanisms of cerebrovascular disease in the HIV population. We hypothesize that dilatation would be present in arterial walls of patients with HIV compared to controls. Fifty-one intracranial arteries, obtained from autopsies of five individuals with HIV infection and 13 without, were fixed, embedded, stained, and digitally photographed. Cross-sectional areas of intima, media, adventitia and lumen were measured by preset color thresholding. A measure of arterial remodeling was obtained by calculating the ratio between the lumen diameter and the thickness of the arterial wall. Higher numbers indicate arterial dilatation, while lower numbers indicate arterial narrowing. HIV-infected brain donors were more frequently black (80% vs. 15%, P = 0.02) compared with uninfected donors. Inter and intra-reader agreement measures were excellent. The continuous measure of vascular remodeling was significantly higher in the arteries from HIV donors (β = 2.8, P = 0.02). Adjustments for demographics and clinical covariates strengthen this association (β = 9.3, P = 0.01). We found an association of HIV infection with outward brain arterial remodeling. This association might be mediated by a thinner media layer. The reproduction of these results and the implications of this proposed pathophysiology merits further study.

Duplex Scanning in Estimation of Arterial Walls in Patients with Non-Specific Aortoarteritis

Duplex Scanning in Estimation of Arterial Walls in Patients with Non-Specific Aortoarteritis

Telmisartan Improves Morphologic and Functional Changes in Both Left Ventricular Myocardium and Carotid Arterial Wall in Patients with Hypertension: Assessment by Tissue Doppler Imaging and Carotid Ultrasonography

The aim of the present study was to clarify the beneficial effects of telmisartan on the morphologic and functional changes in left ventricular (LV) myocardium and carotid arterial wall in patients with hypertension (HT) using tissue Doppler imaging and carotid ultrasonography. Telmisartan (20-40 mg daily) was administered to 35 previously untreated patients with HT. Conventional and pulsed tissue Doppler echocardiography were performed after medication had been continued for 1-2 months with normal values for blood pressure (BP) (phase I) and for 12 months (phase II). Subclinical atherosclerosis also was determined by measuring the intima-media thickness (IMT) and stiffness β of the left and right common carotid arteries using B- and M-mode ultrasonography. In the phase II, the LV mass index and isovolumic relaxation time were lower, the peak systolic and early diastolic mitral annular motion velocities were greater compared to the phase I. The stiffness β and mean IMT were lower in the phase II than in the phase I. On multivariate regression analyses, age, BP, and LV diastolic variables emerged as stronger predictors of carotid arterial IMT and stiffness β. The 1-year use of telmisartan improved LV hypertrophy, regional LV myocardial contraction and relaxation, and carotid atherosclerosis in patients with HT. Our results support cardio- and arterioprotective benefits from continuous long-term telmisartan monotherapy, and combined analysis of tissue Doppler imaging and carotid ultrasonography may be a useful tool for understanding ventriculoarterial coupling in patients with HT.

Does Vascular Calcification Correlate with Pulse Wave Velocity in Hemodialysis Patients?

Vascular calcifications have been previously shown to be an independent predictor of mortality in dialysis patients and a similar association has been shown for arterial stiffness. Nonetheless, the relationship between vascular calcifications and pulse wave velocity (PWV) have so far been little explored. The goal of this study is to verify the correlation among vascular calcifications and rigidity of arterial wall in patients at dialysis start. Accordingly, we investigated the association between aortic PWV and coronary calcification measured by computed tomography (TC-score) in 105 adult incident hemodialysis patients. PWV resulted increased in patients with the higher TC-score values; indeed, at univariate analysis PWV directly correlated with age (p=0.016), presence of diabetes (p&lt;0.0001), serum phosphorus (p=0.0066), C-reactive protein (CRP) (p=0.046), LDL-cholesterol (p=0.043), TC-score (p&lt;0.0001), and inversely correlated with systolic blood pressure (p=0.036). At multivariate analysis, age, diabetes, serum phosphorus, CRP, LDL-cholesterol and vascular calcifications were determinants of arterial stiffening. Using the table “two for two”, we showed 6 false negative patients (high TC-score and low PWV) and 12 false positive patients (low TC-score and high PWV). The sensibility was 76% and the specificity 85%; the accuracy was 83%, the predictor positive value was 61% and the predictor negative value was 92%. Overall, a strong association between TC-score and PWV was seen.

Vascular Wall Remodeling in Patients with Supravalvular Aortic Stenosis and Williams Beuren Syndrome

Supravalvular aortic stenosis (SVAS) and Williams Beuren syndrome (WBS) can be considered as inherited diseases affecting the whole arterial tree and causing narrowing of the vessels. It has been reported that abnormal deposition of elastin in arterial walls of patients with SVAS and WBS leads to increased proliferation of arterial smooth muscle cells (SMC), which result in the formation of hyperplastic intimal lesions. In this work, we conducted morphological and morphometrical analysis with stenotic aortas from patients suffering from SVAS and WBS and from healthy control subjects and demonstrated that the amount of elastic fibers and the loss of integrity of vascular elastic fibers in the aortas reflect similar changes in the skin of patients with SVAS or WBS, as reported in our previous work conducted on skin in these pathological states. On the other hand, we conducted investigations on metalloproteinases (MMP2, MMP9, MMP7) and their specific tissue inhibitors TIMP1 and TIMP2 to verify their possible involvement in the etiopathogeny of SVAS and WBS. We particularly evidenced an altered MMP9/TIMP1 balance in favor of matrix degradation which could facilitate SMC migration and neointimal hyperplasia. Our findings suggest that elastinolytic enzymes secreted by arterial SMC, possibly including matrilysin 1, are critical for the development of arterial lesions in SVAS and WBS and contribute to perpetuate arterial stenosis in either SVAS or WBS.

Generalized arteriopathy in patients with cervical artery dissection

To make an ultrastructural comparison of superficial temporal artery (STA) biopsy specimens from patients with spontaneous cervical artery dissection (sCAD) and controls. The authors used light microscopic examination of semithin sections and electron microscopic examination of ultrathin sections of STA biopsy specimens from patients with sCAD and controls. STA biopsy specimens from patients with sCAD taken around the time of the dissection showed a zone of connective tissue weakening with fissuring at the junction between the tunica media (TM) and the tunica adventitia (TA) in seven of nine specimens and erythrocyte infiltration in eight of nine specimens but in none of the control specimens. Light microscopy demonstrated transparent circular spots that, on electron microscopy, turned out to represent erythrocytes and other cellular components at different stages of degradation. Occasionally, scattered immune cells were found in specimens from patients with sCAD. In addition, smooth muscle cells of the synthetic phenotype, some of them showing extensive vacuolation were more common in the TM of STA biopsy specimens from patients with sCAD than in control specimens. Signs of tissue weakening along the TM/TA junction in STA biopsy specimens of patients with sCAD but not in controls suggest the presence of a generalized arteriopathy leading to impairment of the stability of the arterial wall in patients with sCAD. Limiting factors of the study are that some control biopsies were obtained from autopsies and that the anticoagulation status of patients and controls were not completely comparable.

W17-P-005 Relationship between morphological findings in carotid arteries and mechanical properties of the arterial wall in patients with essential hypertension

W17-P-005 Relationship between morphological findings in carotid arteries and mechanical properties of the arterial wall in patients with essential hypertension

Connection between Elastin Haploinsufficiency and Increased Cell Proliferation in Patients with Supravalvular Aortic Stenosis and Williams-Beuren Syndrome

To elucidate the pathomechanism leading to obstructive vascular disease in patients with elastin deficiency, we compared both elastogenesis and proliferation rate of cultured aortic smooth-muscle cells (SMCs) and skin fibroblasts from five healthy control subjects, four patients with isolated supravalvular aortic stenosis (SVAS), and five patients with Williams-Beuren syndrome (WBS). Mutations were determined in each patient with SVAS and in each patient with WBS. Three mutations found in patients with SVAS were shown to result in null alleles. RNA blot hybridization, immunostaining, and metabolic labeling experiments demonstrated that SVAS cells and WBS cells have reduced elastin mRNA levels and that they consequently deposit low amounts of insoluble elastin. Although SVAS cells laid down approximately 50% of the elastin made by normal cells, WBS cells deposited only 15% of the elastin made by normal cells. The observed difference in elastin-gene expression was not caused by a difference in the stability of elastin mRNA in SVAS cells compared with WBS cells, but it did indicate that gene-interaction effects may contribute to the complex phenotype observed in patients with WBS. Abnormally low levels of elastin deposition in SVAS cells and in WBS cells were found to coincide with an increase in proliferation rate, which could be reversed by addition of exogenous insoluble elastin. We conclude that insoluble elastin is an important regulator of cellular proliferation. Thus, the reduced net deposition of insoluble elastin in arterial walls of patients with either SVAS or WBS leads to the increased proliferation of arterial SMCs. This results in the formation of multilayer thickening of the tunica media of large arteries and, consequently, in the development of hyperplastic intimal lesions leading to segmental arterial occlusion.

Chlamydia pneumoniae DNA in the Arterial Wall of Patients with Peripheral Vascular Disease

Chlamydia pneumoniae is a human respiratory pathogen that has recently been related to the genesis of symptomatic atherosclerosis. C. pneumoniae has been studied more widely in relation to coronary atherosclerosis than to peripheral arterial occlusive disease (PAOD). The present study aimed to retrospectively analyze the presence of C. pneumoniae DNA in patients with PAOD. A seminested PCR method was applied on 85 samples from 71 patients with PAOD secondary to surgical treatment. The control group comprised 50 patients with chronic superficial venous insufficiency who required varicose resection surgery. The number of patients, number of samples studied and percentage of patients found to be positive in the PCR study were 17, 18 and 59%, respectively, for arteries of the lower extremities; 15, 16 and 60% for aneurysm of the abdominal aorta; 22, 23 and 73% for carotid stenosis and 17, 18 and 65% for aortic stenosis. C. pneumoniae DNA was found in six external pudendal arteries (12%) of the control group, significantly lower than the incidence in the patient group (p < 0.0001). A causal relationship between chronic C. pneumoniae infection and PAOD cannot be ruled out. On the contrary, the high incidence of C. pneumoniae DNA detected in our patients suggests that C. pneumoniae infection may play some role in the pathogenesis of peripheral vascular disease.

Attenuation by Fibrates of Plasminogen Activator Inhibitor Type-1 Expression in Human Arterial Smooth Muscle Cells

Human atherosclerotic lesions exhibit increased expression of plasminogen activator inhibitor type-1 (PAI-1) that has been implicated in atherogenesis. Although vascular smooth muscle cells are a predominant source of PAI-1 expression potentially favorable modulation of PAI-1 expression by fibrates has not yet been characterized in these cells. Human aortic smooth muscle cells were exposed to selected growth factors. PAI-1 expression was stimulated most powerfully by TGF-beta (EC50 = 0.2 ng/ml, up to 12-fold increase). Gemfibrozil inhibited basal PAI-1 expression by 23% (p = ns) and TGF-beta-induced PAI-1 expression by 52% (p = 0.017) whereas t-PA and total protein synthesis was not affected. Changes in PAI-1 protein accumulation reflected PAI-1 gene expression attributable to modulation of half-life of PAI-1 mRNA by gemfibrozil. Inhibition by other fibrates was less. Gemfibrozil specifically attenuates TGF-beta-induced PAI-1 expression in human arterial smooth muscle cells. Thus, fibrates are promising agents for normalizing increased PAI-1 expression in arterial walls in patients in whom PAI-1 expression is increased.

Changes in the arterial wall in patients with essential hypertension

Changes in the arterial wall in patients with essential hypertension

Insulin resistance and systemic hypertension

There is a complex relation among insulin sensitivity, hypertension, and endothelial function. Although there are few prospective data on the relation between insulin levels and the development of hypertension, there is some evidence that insulin resistance precedes the onset of established hypertension in high-risk patients. Because insulin is a vasodilator, it would need to activate a variety of other potential physiologic mechanisms to play a causal role in the pathogenesis of hypertension. There are changes in the arterial wall in patients with hyperinsulinemia, and characteristic decreases in elasticity of the arterial wall have been noted in hypertensive patients with insulin resistance. Hyperglycemia, hyperinsulinemia, and hypertriglyceridemia appear to jointly contribute to increased arterial stiffness. There are, however, ethnic and racial disparities in the association of insulin, insulin sensitivity, and blood pressure, as this relation is not strongly observed in the black population in the United States and elsewhere. This may reflect complex relations among obesity, diabetes, and hypertension, which are more common in patients with African ancestry, although recent evidence supports the probability that the differences are genetically determined. Whatever the precise mechanisms, clinical investigations demonstrate the benefit of early interventions to improve insulin sensitivity and control hypertension, as well as to reduce hypercholesterolemia. In particular, enhanced insulin sensitivity may improve hypertension and its subsequent damage to vessel walls.

Cytomegalovirus DNA in arterial walls of patients with atherosclerosis.

The biological properties of cytomegalovirus (CMV) are consistent with a potential role in the pathogenesis of atherosclerosis. The evidence of such a role has so far been circumstantial, but CMV nucleic acid is beginning to be reported with increasing frequency in the arterial wall. Arterial specimens from 135 patients who underwent vascular surgery for symptomatic atherosclerotic vessel disease were analyzed by PCR for the presence of CMV nucleic acid. Samples were studied from the atheromatous plaque area and from uninvolved aortic tissues of patients undergoing surgery for vascular disease. One primer pair (LA) was used for detection of a late gene, and two other primer pairs (E1 and E2) were used for the immediate early gene region. Serum antibody to CMV was measured by radioimmunoassay. With the late gene primer, CMV nucleic acid was found in 76% of the tissue specimens tested, whereas the E2 gene primer complementary to the transforming mtr2 region was reactive in 90% of the arterial samples. There was no significant difference in the prevalence of CMV DNA in atherosclerotic plaque tissue and in uninvolved aortic tissue from the patients. A second early gene primer was not reactive with the tissue specimens, although it gave positive results with the positive control of infectious virus. Serum antibody to CMV was detected in 86% of the patients in whose tissue CMV DNA was demonstrated. CMV DNA was detected in a high proportion of atherosclerotic plaque tissues as well as in uninvolved aortic tissue of surgical patients, suggesting that latent CMV infection of the arterial wall may be a common occurrence in patients with atherosclerosis.

T cell subsets and expression of immunological activation markers in the arterial walls of patients with giant cell arteritis.

Immunohistochemical features of infiltrating mononuclear cells (MNC) and resident cells were studied in the temporal artery biopsy specimens of 13 patients with histological verified giant cell arteritis (GCA) and in six biopsy specimens from patients with GCA with negative histological findings. Eight temporal artery biopsy specimens from seven patients with unrelated diseases served as controls. In all patients with GCA proved by biopsy an infiltration of T lymphocytes in the arterial wall was observed, most being of the helper/inducer subset. No B lymphocytes, or very few, were seen. Lymphocytes in 10 out of the 13 positive biopsy specimens displayed staining for the class II major histocompatibility complex (MHC) antigen HLA-DR, whereas this was found in only two of eight controls. A minor number of the infiltrating T lymphocytes from seven out of 13 patients with GCA proved by biopsy stained for transferrin receptors, and in six out of the 13 cases they reacted with anti-interleukin 2 receptor antibody. In the arterial wall from all patients with histologically verified GCA we also found an increased number of macrophages, many of them expressing HLA-DR antigens and transferrin receptors. The immunohistochemical pattern of cell phenotypes found in the arterial wall of patients with GCA suggests that the infiltrating T cells are immunologically activated. This finding supports the hypothesis of a predominantly cellular immunological pathogenesis of giant cell arteritis.

Altered 1-14C Arachidonic Acid Metabolism in Arterial Wall from Patients with Renal Cell Carcinoma

The metabolism of 1-14C arachidonic acid (AA) by arterial wall in patients with renal cell carcinoma and in control patients undergoing nephrectomy was investigated by a high pressure liquid chromatography (HPLC) system.No differences in 1-14C AA uptake and in the total amount of metabolites were found between the two groups, whereas the amounts of cyclooxygenase and lipoxygenase pathway (COP and LOP) metabolites produced by patients with renal cell carcinoma were significantly lower and, respectively, higher than those produced by the control group. The COP/LOP ratio was 7.2±5.5 in the control group in comparison to 1.9±0.5 in renal cell carcinoma patients. The decrease in COP metabolites was due to a markedly reduced synthesis of prostacyclin (PGI2), with no changes in thromboxane B2 (TxB2), prostaglandin F2α (PGF2α) and prostaglandin E2 (PGE2) production. The changes in PGI2 and 12-hydroxy-eicosatetraenoic acid (12-HETE) (metabolite of LOP) vascular production were not related to tumor dimension.The decrease in PGI2 synthesis may represent a factor favoring metastasis and thrombosis in neoplastic patients.