Paradoxical Effect of Nonalcoholic Red Wine Polyphenol Extract, Provinols™, in the Regulation of Cyclooxygenases in Vessels from Zucker Fatty Rats (fa/fa)

The aim of this work was to study the vascular effects of dietary supplementation of a nonalcoholic red wine polyphenol extract, Provinols, in Zucker fatty (ZF) obese rats. ZF or lean rats received diet supplemented or not with Provinols for 8 weeks. Vasoconstriction in response to phenylephrine (Phe) was then assessed in small mesenteric arteries (SMA) and the aorta with emphasis on the contribution of cyclooxygenases (COX). Although no difference in vasoconstriction was observed between ZF and lean rats both in SMA and the aorta, Provinols affected the contribution of COX-derived vasoconstrictor agents. The nonselective COX inhibitor, indomethacin, reduced vasoconstriction in vessels from both groups; however, lower efficacy was observed in Provinols-treated rats. This was associated with a reduction in thromboxane-A2 and 8-isoprostane release. The selective COX-2 inhibitor, NS398, reduced to the same extent vasoconstriction in aortas from ZF and Provinols-treated ZF rats. However, NS398 reduced response to Phe only in SMA from ZF rats. This was associated with a reduction in 8-isoprostane and prostaglandin-E release. Paradoxically, Provinols decreased COX-2 expression in the aorta, while it increased its expression in SMA. We provide here evidence of a subtle and paradoxical regulation of COX pathway by Provinols vessels from obese rats to maintain vascular tone within a physiological range

Long-Term Intranasal Nerve Growth Factor Treatment Favors Neuron Formation in de novo Brain Tissue

ObjectiveTo date, no safe and effective pharmacological treatment has been clinically validated for improving post-stroke neurogenesis. Growth factors are good candidates but low safety has limited their application in the clinic. An additional restraint is the delivery route. Intranasal delivery presents many advantages.Materials and MethodsA brain lesion was induced in twenty-four rats. Nerve growth factor (NGF) 5 μg/kg/day or vehicle was given intranasally from day 10 post-lesion for two periods of five weeks, separated by a two-week wash out period with no treatment. Lesion volume and atrophy were identified by magnetic resonance imaging (MRI). Anxiety and sensorimotor recovery were measured by behavior tests. Neurogenesis, angiogenesis and inflammation were evaluated by histology at 12 weeks.ResultsRemarkable neurogenesis occurred and was visible at the second and third months after the insult. Tissue reconstruction was clearly detected by T2 weighted MRI at 8 and 12 weeks post-lesion and confirmed by histology. In the new tissue (8.1% of the lesion in the NGF group vs. 2.4%, in the control group at 12 weeks), NGF significantly increased the percentage of mature neurons (19% vs. 7%). Angiogenesis and inflammation were not different in the two groups. Sensorimotor recovery was neither improved nor hampered by NGF during the first period of treatment, but NGF treatment limited motor recovery in the second period.InterpretationThe first five-week period of treatment was very well tolerated. This study is the first presenting the effects of a long treatment with NGF and has shown an important tissue regeneration rate at 8 and 12 weeks post-injury. NGF may have increased neuronal differentiation and survival and favored neurogenesis and neuron survival through subventricular zone (SVZ) neurogenesis or reprogramming of reactive astrocytes. For the first time, we evidenced a MRI biomarker of neurogenesis and tissue reconstruction with T2 and diffusion weighted imaging

Increased mean aliphatic lipid chain length in left ventricular hypertrophy secondary to arterial hypertension: A cross-sectional study

About 77.9 million (1 in 4) American adults have high blood pressure. High blood pressure is the primary cause of left ventricular hypertrophy (LVH), which represents a strong predictor of future heart failure and cardiovascular mortality. Previous studies have shown an altered metabolic profile in hypertensive patients with LVH. The goal of this study was to identify blood metabolomic LVH biomarkers by H NMR to provide novel diagnostic tools for rapid LVH detection in populations of hypertensive individuals. This cross-sectional study included 48 hypertensive patients with LVH matched with 48 hypertensive patients with normal LV size, and 24 healthy controls. Two-dimensional targeted M-mode echocardiography was performed to measure left ventricular mass index. Partial least squares discriminant analysis was used for the multivariate analysis of the H NMR spectral data. From the H NMR-based metabolomic profiling, signals coming from methylene (-CH2-) and methyl (-CH3) moieties of aliphatic chains from plasma lipids were identified as discriminant variables. The -CH2-/-CH3 ratio, an indicator of the mean length of the aliphatic lipid chains, was significantly higher (P < 0.001) in the LVH group than in the hypertensive group without LVH and controls. Receiver operating characteristic curve showed that a cutoff of 2.34 provided a 52.08% sensitivity and 85.42% specificity for discriminating LVH (AUC = 0.703, P-value < 0.001). We propose the -CH2-/-CH3 ratio from plasma aliphatic lipid chains as a biomarker for the diagnosis of left ventricular remodeling in hypertension

Red wine polyphenols prevent metabolic and cardiovascular alterations associated with obesity in Zucker fatty rats (Fa/Fa)

Peer reviewedPublisher PD

Blood Signature of Pre-Heart Failure: A Microarrays Study

International audienceBACKGROUND: The preclinical stage of systolic heart failure (HF), known as asymptomatic left ventricular dysfunction (ALVD), is diagnosed only by echocardiography, frequent in the general population and leads to a high risk of developing severe HF. Large scale screening for ALVD is a difficult task and represents a major unmet clinical challenge that requires the determination of ALVD biomarkers. METHODOLOGY/PRINCIPAL FINDINGS: 294 individuals were screened by echocardiography. We identified 9 ALVD cases out of 128 subjects with cardiovascular risk factors. White blood cell gene expression profiling was performed using pangenomic microarrays. Data were analyzed using principal component analysis (PCA) and Significant Analysis of Microarrays (SAM). To build an ALVD classifier model, we used the nearest centroid classification method (NCCM) with the ClaNC software package. Classification performance was determined using the leave-one-out cross-validation method. Blood transcriptome analysis provided a specific molecular signature for ALVD which defined a model based on 7 genes capable of discriminating ALVD cases. Analysis of an ALVD patients validation group demonstrated that these genes are accurate diagnostic predictors for ALVD with 87% accuracy and 100% precision. Furthermore, Receiver Operating Characteristic curves of expression levels confirmed that 6 out of 7 genes discriminate for left ventricular dysfunction classification. CONCLUSIONS/SIGNIFICANCE: These targets could serve to enhance the ability to efficiently detect ALVD by general care practitioners to facilitate preemptive initiation of medical treatment preventing the development of HF

Evaluation de deux nouveaux outils pour l'étude d'échantillons biologiques par spectroscopie de résonance magnétique nucléaire (la RMN HR-MAS (High-Resolution Magic Angle Spinning) : une technique d'analyse d'échantillons bruts, La Métabonomique : une méthode d'analyse statistique des spectres pour la recherche de signatures métaboliques)

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Atlas statistique de la vascularisation cérébrale chez le singe marmouset

International audienc

Effect of ageing on the cerebral hemodynamics in the marmoset monkey

International audienceAimCerebrovascular function declines during normal ageing and appears to be closely linked to brain functionalteration in the elderly. We adapted dedicated MRI sequences to analyze blood flow dynamics in arterial andvenous intracranial vessels, using a non-human primate model of significant interest for preclinical research, themarmoset monkey Callithrix jacchus.MethodsImaging sequences were acquired on a 7T MRI (Bruker Biospec, voxel size: 0,15x0,15X1mm3) on two groups ofmale and female marmosets: 10 young (4 years old) and 9 aged (9 years old). Internal carotid arteries, basilarartery, superior and inferior sagittal sinuses were first identified by Time Of Flight (TOF) sequences and flowvelocity in these different vessels was recorded by Phase Contrast (PC) MRI synchronized with ECG signal.ResultsThe main significant results show that during the cardiac cycle:-The blood flow peaks earlier in the basilary trunk than in the carotids.-The arterial flow peak occurs earlier in the aged than in the young marmoset brains.-The time interval between the arterial- and the venous flow peaks is shorter in old than in young marmosets.ConclusionsThese results reflect vessel rigidity and tissue compliance changes occurring during ageing in the vascularnetwork. They have not been shown in human studies, in which blood flow dynamics are usually synchronizedwith peripheral pulse measured on the fingertip. They suggest that the time courses of the different vascularflows could contribute as early markers of brain ageing and brain pathologies

Effect of ageing on the cerebral hemodynamics in the marmoset monkey

International audienceAimCerebrovascular function declines during normal ageing and appears to be closely linked to brain functionalteration in the elderly. We adapted dedicated MRI sequences to analyze blood flow dynamics in arterial andvenous intracranial vessels, using a non-human primate model of significant interest for preclinical research, themarmoset monkey Callithrix jacchus.MethodsImaging sequences were acquired on a 7T MRI (Bruker Biospec, voxel size: 0,15x0,15X1mm3) on two groups ofmale and female marmosets: 10 young (4 years old) and 9 aged (9 years old). Internal carotid arteries, basilarartery, superior and inferior sagittal sinuses were first identified by Time Of Flight (TOF) sequences and flowvelocity in these different vessels was recorded by Phase Contrast (PC) MRI synchronized with ECG signal.ResultsThe main significant results show that during the cardiac cycle:-The blood flow peaks earlier in the basilary trunk than in the carotids.-The arterial flow peak occurs earlier in the aged than in the young marmoset brains.-The time interval between the arterial- and the venous flow peaks is shorter in old than in young marmosets.ConclusionsThese results reflect vessel rigidity and tissue compliance changes occurring during ageing in the vascularnetwork. They have not been shown in human studies, in which blood flow dynamics are usually synchronizedwith peripheral pulse measured on the fingertip. They suggest that the time courses of the different vascularflows could contribute as early markers of brain ageing and brain pathologies

Le singe marmouset comme modèle humain : Effet du vieillissement sur l'hémodynamique cérébrale.

International audienc