Search

Purpose: Vascular calcification was considered to be a passive, degenerative, and end-stage process of vascular disease. However, bone associated proteins such as bone morphogenetic proteins, osteopontin, osteonectin, ostcocalcin, and matrix Gla protein (MGP) have been found in the calcified atherosclerotic lesions. We studied by microarray analysis whether intact tissue and carotid plaque from the same patient differ in transcriptional profiling in response to arterial calcification. Material and Methods: mRNA gene expression was measured by an Affymetrix GeneChip Human Gene 1.0 ST arrays (Affymetrix, Santa Clara, CA, USA) using RNA prepared from 68 specimens of endarterectomy from 34 patients. Results: Integrin-binding sialoprotein (IBSP) was found to be differentially expressed. IBSP mRNA is over expressed in atheroma plaque (3.74 fold, p = 1.41E-09) in an intraindividual comparison. Besides, Carbonic anhydrase II (CA2) Which known to be a putative calcification inhibitory molecule is over expressed more than 1.7 fold in carotid plaque (p = 1.26E-06). Conclusion: Although further evidence is needed, our results support previously available data. To our knowledge, this is the first report comparing gene expression between intact arterial tissue and carotid plaque using microarray analysis in order to identify calcification related genes. We suggest that plaques show a more pronounced induction of IBSP that may cause arterial calcification. [ABSTRACT FROM AUTHOR]

Current antihypertensive strategies do not take into account that individual characteristics may influence the magnitude of blood pressure (BP) reduction. Guidelines promote trial-and-error approaches with many different drugs. We conducted the Identification of the Determinants of the Efficacy of Arterial blood pressure Lowering drugs (IDEAL) Trial to identify factors associated with BP responses to perindopril and indapamide. IDEAL was a cross-over, double-blind, placebo-controlled trial, involving four 4-week periods: indapamide, perindopril and two placebo. Eligible patients were untreated, hypertensive and aged 25-70 years. The main outcome was systolic BP (SBP) response to drugs. The 112 participants with good compliance had a mean age of 52. One in every three participants was a woman. In middle-aged women, the SBP reduction from drugs was −11.5 mm Hg (indapamide) and −8.3 mm Hg (perindopril). In men, the response was significantly smaller: −4.8 mm Hg (indapamide) and −4.3 (perindopril) (P for sex differences 0.001 and 0.015, respectively). SBP response to perindopril decreased by 2 mm Hg every 10 years of age in both sexes (P=0.01). The response to indapamide increased by 3 mm Hg every 10 years of age gradient in women (P=0.02). Age and sex were important determinants of BP response for antihypertensive drugs in the IDEAL population. This should be taken into account when choosing drugs a priori. [ABSTRACT FROM AUTHOR]

Aim: We report the first experience of Lyon's university hospital regarding renal denervation to treat patients with resistant essential hypertension. Patients and methods: Over a one-year period, 17 patients were treated (12 men, 5 women) with renal denervation. Baseline characteristics were as follows: age 56.5 ± 11.5 years, BMI 33 ± 5 kg/m² and ambulatory blood pressure 157 ± 16/87 ± 13 mmHg with 4.2 ± 1.5 anti-hypertensive treatment. Results: We did not observe per procedural and early complications. After a median follow-up of 3 months and with the same anti-hypertensive treatment, office systolic blood pressure (SBP) and diastolic blood pressure (DBP) decrease respectively of 20 ± 15 (P < 0.001) and 10 ± 13 mmHg (P = 0.014) (n = 17). After six months of follow-up, ambulatory blood pressure (ABPM) decrease of 17.5 ± 14.9 mmHg (P = 0.027) for SBP and of 10.5 ± 9.6 mmHg (P = 0.029) for DBP (n = 6). Among these patients, five of them were controlled (ABPM inferior to 130/80 mmHg) and electrical left ventricular hypertrophy indexes decreased: R wave in aVL lead of 4 ± 3 mm (P = 0.031), Sokolow index of 3 ± 3 mm (P = 0.205), Cornell voltage criterion of 9 ± 7 mm (P = 0.027) and Cornell product of 1310 ± 1104 (P = 0.027). Conclusion: Our results are in accordance with data from other centers. On average blood pressure decreases significantly but important inter individual variations are observed. The procedure seems safe. [ABSTRACT FROM AUTHOR]

Abstract: An overwhelming nitric oxide (NO) production is a crucial step in the circulatory events as well as in the cellular alterations taking place in septic shock. However, evidences of this role arise from studies assessing the NO production on an intermittent basis precluding any clear evaluation of temporal relationship between NO production and circulatory alterations. We evaluated this relationship by using a NO specific electrode allowing a continuous measurement of NO production. Septic shock was induced by a cecal ligation and puncture (CLP) in a first group of anesthetized rats. After the same CLP, a second group received a selective iNOS inhibitor (L-NIL). Control rats were sham operated or sham operated with L-NIL administration. While NO concentration was measured every 2min by a NO-sensitive electrode over 7h following CLP, the liver microcirculation was recorded by a laser-Doppler flowmeter. CLP induced a severe septic shock with hypotension occurring at a mean time of 240min after CLP. At the same time, an increase in liver NO concentration was observed, whereas a decrease in microvascular liver perfusion was noted. In the septic shock group, L-NIL administration induced an increase in arterial pressure whereas the liver NO concentration returned to baseline values. In addition, shock groups experienced an increase in iNOS mRNA. These data showed a close temporal relationship between the increase in liver NO concentration and the microvascular alteration taking place in the early period of septic shock induced by CLP. The iNOS isoform is involved in this NO increase. [ABSTRACT FROM AUTHOR]

Summary: Williams–Beuren syndrome (WBS) (OMIM# 194050) is a rare, most often sporadic, genetic disease caused by a chromosomal microdeletion at locus 7q11.23 involving 28 genes. Among these, the elastin gene codes for the essential component of the arterial extracellular matrix. Developmental disorders usually associate an atypical face, cardiovascular malformations (most often supravalvular aortic stenosis and/or pulmonary artery stenosis) and a unique neuropsychological profile. This profile is defined by moderate mental retardation, relatively well-preserved language skills, visuospatial deficits and hypersociability. Other less known or rarer features, such as neonatal hypercalcemia, nutrition problems in infancy, ophthalmological anomalies, hypothyroidism, growth retardation, joint disturbances, dental anomalies and hypertension arising in adolescence or adulthood, should be treated. The aim of this paper is to summarize the major points of WBS regarding: (i) the different genes involved in the deletion and their function, especially the elastin gene and recent reports of rare forms of partial WBS or of an opposite syndrome stemming from a microduplication of the 7q11.23 locus, (ii) the clinical features in children and adults with a focus on cardiovascular injury, and (iii) the specific neuropsychological profile of people with WBS through its characteristics, the brain structures involved, and learning. [Copyright &y& Elsevier]

Uptake of modified low-density lipoproteins (LDLs) by macrophages in the arterial wall is an important event in atherogenesis. Indeed, oxidatively modified LDLs (oxLDLs) are known to affect various cellular processes by modulating oxidation-sensitive signaling pathways. Here we found that the ubiquitous 55 kDa selenoprotein thioredoxin reductase 1 (TrxR1), which is a key enzyme for cellular redox control and antioxidant defense, was upregulated in human atherosclerotic plaques and expressed in foam cells. Using reverse transcription polymerase chain reaction analysis, we also found that oxLDLs, but not native LDLs (nLDLs), dose-dependently increased TrxR1 mRNA in human monocyte-derived macrophages (HMDMs). This stimulating effect was specific for oxLDLs, as pro-inflammatory factors, such as lipopolysaccharides (LPSs), interleukin-1β (IL-1β), interleukin-6 (Il-6), and tumor necrosis factor α (TNFα), under the same conditions, failed to induce TrxR1 mRNA levels to the same extent. Moreover, phorbol ester-differentiated THP-1 cells or HMDMs transiently transfected with TrxR1 promoter fragments linked to a luciferase reporter gene allowed identification of a defined promoter region as specifically responding to the phospholipid component of oxLDLs (p < .05 vs. phospholipid component of nLDLs). Gel mobility shift analyses identified a short 40-nucleotide stretch of the promoter carrying AP-1 and HoxA5 consensus motifs that responded with an altered shift pattern in THP-1 cells treated with oxLDLs, however, without evident involvement of either the Fos, Jun, Nrf2 or HoxA5 transcription factors. [Copyright &y& Elsevier]

Presents a letter to the editor regarding the peroxysome proliferator-activated receptors' gene expression in Type 2 diabetic atheroma published in the September 2004 issue of the "European Journal of Clinical Investigation."

Objectifs: La perte de fonction du récepteur V2 de la vasopressine se traduit par un diabète insipide néphrogénique congénital (DINc) lié à l’X, pathologie à ce jour bien connue. Par contre, ce n’est qu’en 2005 que deux mutations responsables d’une activité constitutive des récepteurs de la vasopressine ont été découvertes in vivo. Ce nouveau syndrome a été qualifié de nephrogenic syndrome of inappropriate antidiuresis Sujets: À ce jour, douze patients de sexe masculin atteints de NSIAD et neuf femmes transmettrices ont été décrits. Résultats: La présentation clinique des patients étudiés se fait le plus souvent par des convulsions hyponatrémiques se révélant tôt dans l’enfance. Au niveau biologique, le tableau est évocateur d’un syndrome de sécrétion inappropriée d’hormone antidiurétique (SIADH) mais avec un dosage plasmatique de vasopressine bas ou effondré. La connaissance des signes cliniques et biologiques du NSIAD ainsi qu’une information médicale ciblée devrait permettre de diagnostiquer cette pathologie chez un grand nombre de sujets atteints, d’éviter ainsi la récidive de convulsions pouvant entraîner des séquelles neurologiques irréversibles et d’estimer sa fréquence, probablement sous-estimée. (NSIAD) ou syndrome d’antidiurèse inappropriée néphrogénique. [ABSTRACT FROM AUTHOR]