M. FREIDJA Mohamed lamine

Background: Frying oil lipids are prone to oxidation, so aromatic plants and their essential oils (EOs) have been applied to prevent this process. This study aimed to incorporate the grapefruit (Citrus x paradisi) EO in sunflower frying oil to protect it against oxidation. Before enrichment, a cytotoxicity test was performed to determine the non-cytotoxic concentration of this EO.
Methods: Cell viability was evaluated using the MTT-based cytotoxicity assay. Various EO concentrations (0.01-0.5 mg/ml) were added to cultured cells Human Umbilical Vein Endothelial Cells (HUVECs) and Human Stellar Hepatic Cell lines LX-2 (SCC064) and incubated for 24 and 48 h. The stability of sunflower oil during frying was assessed by determining several parameters including peroxide value, polar compounds, and free fatty acids. Results: The obtained IC50 values after 24 h were 0.276 and 0.200 mg/ml for LX-2 and HUVECs cells, respectively, and the results after 48 h were 0.269 and, 0.216 mg/ml, respectively. Following that, the appropriate concentration of EO was incorporated into the sunflower oil. An oxidation acceleration test demonstrated that the lowest concentration of EO provided the best oxidation resistance (14 h 59 min) comparatively to the unfortified sunflower oil (11 h 63 min). The stability of enriched oil polar compounds during repeated frying was also noticed. Conclusion: The incorporation of this EO into sunflower oil during a deep-frying process led to a significant increase in its oxidative stability; therefore, it can be used as a food additive.
Keywords: Citrus X Paradisi, Volatile, Oils, Antioxidant, Toxicity test, Sunflower oil.

La biologie moléculaire est une discipline scientifique au croisement de la génétique, de la biochimie et de la physique.
Pour une analyse performante des acides nucléiques par les techniques de biologie molécualire, nous avons besoin de respecter un protocole rigoureux afin d'obtenir un extrait de qualité.
Cette formation était une occasion d'exposer les différentes étapes de préparation des acides nucléiques. Elle a été animée devant des étudiants en fin de cycle, notamment M2, pour leur permettre de découvrir cette descipline si importante dans leur projet professionnel.

L'extraction des acides nucléiques (AN) passe par différents protocoles expérimentaux qui suivent tous le même schéma:
- Lyse cellulaire,
- Elimination des protéines et des lipides,
- Elimination des autres AN
Les Kits commerciaux sont actuellement les plus utilisés pour une meilleure efficacité et dans un but d'éviter les contaminations.

Roasting is a key step for preparing sesame oil that leads to important changes in its organoleptic properties and quality. In this study, white sesame seeds were roasted for 20 min in an electric oven at different temperatures (120, 150, 180, 210, 250 and 300 °C). The oils extracted from unroasted and roasted seeds were compared for their chemical composition: fatty acids (including trans isomers), phytosterols, lignans (sesamin and sesamolin), tocopherols and total phenolic compounds, as well as their oxidative stability and antiradical capacity. There were no obvious differences in the oil densities, refractive indexes or iodine values, but the saponification values were affected by temperature. Relevant primary and secondary lipid oxidation were observed at T > 250 °C, resulting in a higher p-anisidine value and K232 as well as K268 values. Roasting improved oil yield (from 33.5 to 62.6%), increased its induction period (from 5.5 to 10.5 h) and enhanced the total phenolic content (from 152 to 194 mg/100 g) and antiradical activity of the extracted oil. Depending on roasting temperature, a gradual decline was recorded in total amounts of phytosterols (up to 17.4%), γ-tocopherol (up to 10.6%), sesamolin (maximum of 27.5%) and sesamin (maximum of 12.5%). All the investigated oils presented a low quantity in triglyceride polymers, clearly below the maximum tolerated quantity according to the European regulation. The optimal roasting temperature for obtaining high nutritional grade oil within the permissible values was 210 °C. The unsaponifiable components (including lignans and sterols) extracted from roasted seeds have been shown to be natural additives to fresh meatball products to extend shelf life. The results of this study may help to boost the nutritional content of plant-based diets by allowing for the use of roasted sesame seed oil and its components.

Elaborer des méthodes par modélisation prédictive
Enjeux économiques qui y sont liés sont importants (industriels, public)
Modélisation est avant tout une affaire d’informatique (systèmes peu complexes)
Systèmes vivants (hyper-complexes): => Modélisation est une affaire de biologie assistée par l’informatique

Conclusion
La modélisation prédictive est très utile
Systèmes vivants sont hyper-complexes (Systèmes intégratifs et non linéaires)
Savoir utiliser les bases de données informationnelles

La sarriette est une plante médicinale appartient à la famille des lamiacées. Dans cette étude, nous avons intéressées de Satureja montana des monts de Maadid (région de Hodna). Deux extraits bruts ont été préparés à partir de la partie aérienne : L’un méthanolique et l’autre aqueux. Les rendements d’extraction sont de l’ordre de 09,78 % et 18,7% respectivement. Les tests phytochimiques appliquées au Satureja montana ont montré la présence de plusieurs familles de composés chimiques potentiellement bioactives, notamment les flavonoïdes et les tanins. L’estimation quantitative des phénols totaux, flavonoïdes, flavones et flavonols par les méthodes colorimétriques a montré que l’extrait méthanolique est plus riche en ces composés par rapport l’extrait aqueux. L’activité antioxydante a été évaluée par trois méthodes : Le piégeage de radical libre DPPH• dont les IC50 ont été estimées à 31,65 ± 0,33 et 34,88 ± 0,16 μg/ml pour l’extraits méthanolique et aqueux respectivement et qui sont inférieures à celle obtenue par le BHT (21,67 ± 0,21 μg/ml). La capacité antioxydante totale (TAC) est estimée à 172, 97 ± 2,89 μg EAA/mg pour l’extrait méthanolique et 266, 15 ± 8,35 μg EAA/mg pour l’extrait aqueux. Pour le test de réduction du fer (FRAP), les EC50 montrent un pouvoir réducteur de l’ordre de : 98,71 ± 0,70 μg/ml (acide ascorbique), 366,27 ± 2,94 μg/ml (extrait méthanolique) et 461,52 ± 0,47μg/ml (aqueux). L’activité antibactérienne est déterminée vis-à-vis de deux souches bactériennes de référence, selon la méthode de diffusion dans les puits. Les résultats obtenus ont montrés que les deux extraits ont un effet sur la souche Escherichia coli, alors que l’extrait méthanolique seulement possède un effet sur la souche Bacillus cereus.

La sarriette est une plante médicinale qui appartient à la famille des lamiacées. Dans cette étude, nous nous sommes intéressées au Satureja calamintha des monts de Maadid (région de Hodna).
Deux extraits bruts ont été préparés à partir de la partie aérienne : l’un obtenu par décoction (EDéc) et l’autre par extraction aux micro-ondes (EMO). Les rendements d’extraction sont de l’ordre de 17,5 ± 0,5 % et 21,83 ± 0,7 % respectivement. Les tests phytochimiques appliquées aux extraits de Satureja calamintha ont montré la présence de plusieurs familles de composés chimiques potentiellement bioactives, notamment les flavonoïdes et les tanins. L’estimation quantitative des polyphénols totaux et des flavonoïdes par méthode colorimétrique a montré que EDéc est plus riche en métabolites secondaires par rapport à EMO. L’activité antioxydante a été évaluée par deux méthodes : i) le piégeage du radical libre DPPH avec des IC50 à 24,77 ± 0,76 et 23,07 ± 0,18 µg/ml pour EDéc et EMO respectivement et qui sont supérieures à celle obtenue par le BHT (22,25 ± 1,24 µg/ml) ; ii) La capacité antioxydante totale (TAC) est estimée à 84,64 ± 0,72 µg EAA/mg pour EDéc et 80,41 ± 19,13 µg EAA/mg pour EMO.
L’activité antibactérienne est déterminée vis-à-vis de deux souches bactériennes de référence : Escherichia coli (Gram négatif) et Bacillus subtillus (Gram positive), selon la méthode de diffusion dans les disques. Les deux extraits n’ont montré aucun effet sur la souche E. coli, Cependant, ils possèdent un effet inhibiteur modéré sur la souche B. subtillus.

Pallenis spinosa is a medicinal plant which is used in folk medicine as curative or preventive remedies for various diseases. Individual phenolic compounds from the methanolic extracts of its flowers, leaves and stem were determined by the high performance liquid chromatography method (HPLC) and total phenolic contents (TPC) were evaluated by Folin–Ciocalteu assay. The stability and bioactivity (antioxidant activity, micellar cholesterol solubility, α-amylase, and angiotensin converting enzymes (ACE) inhibitory effects) of these extracts in the gastrointestinal environment was determined before and after their protection in hydroxypropylmethylcellulose (HPMC) capsules. HPLC analysis revealed the presence of thirteen phenolic compounds with nine flavonoids and four phenolic acids. Except for kaempferol, the twelve other compounds have not been previously detected in the aerial part of the studied plant. Quantification of phenolics by HPLC and Folin Ciocalteu methods revealed that the highest TPC was detected in the flower extracts (104.31 ± 0.80 and 145.73 ± 0.48 mg EGA per g of extract, respectively). Leaf extracts displayed the best antioxidant capacity against the two tested radicals DPPH and ABTS (IC50 = 1.24 ± 0.03 and 0.94 ± 0.02 mg mL−1, respectively), FRAP assay (IC50 = 0.50 ± 0.02 mg mL−1), α-amylase inhibitory (IC50 = 1.25 ± 0.00 mg mL−1) and angiotensin activity with an inhibitory percent of 30.10 ± 0.12%. The best activity shown by stem extracts was against micellar cholesterol solubility (67.57 ± 0.00%). A strong decrease in TPC and their bioactivity was observed after the gastrointestinal digestion (GID) in non encapsulated extracts. These results showed that P. spinosa is a good source of phenolic compounds and GID affects significantly their composition, content and bioactivity.

Chronic Obstructive Pulmonary Disease is a generally smoking-linked major cause of morbidity and mortality. Genome-wide Association Studies identified a locus including a non-synonymous single nucleotide polymorphism in CHRNA5, rs16969968, encoding the nicotinic acetylcholine receptor α5 subunit, predisposing to both smoking and Chronic Obstructive Pulmonary Disease. Here we report that nasal polyps from rs16969968 non-smoking carriers exhibit airway epithelium remodeling and inflammation. These hallmarks of Chronic Obstructive Pulmonary Disease occur spontaneously in mice expressing human rs16969968. They are significantly amplified after exposure to porcine pancreatic elastase, an emphysema model, and to oxidative stress with a polymorphism-dependent alteration of lung function. Targeted rs16969968 expression in epithelial cells leads to airway remodeling in vivo, increased proliferation and production of pro-inflammatory cytokines through decreased calcium entry and increased adenylyl-cyclase activity. We show that rs16969968 directly contributes to Chronic Obstructive Pulmonary Disease-like lesions, sensitizing the lung to the action of oxidative stress and injury, and represents a therapeutic target.

The beneficial effects of sesame seeds are of great interest for the conception of healthy dairy products such as probiotic stirred yogurt. We investigated the effects of adding raw or roasted sesame seeds on the probiotic viability, quality parameters and consumers acceptability of stirred yogurt during 28 days cold storage (4 °C). All yogurts were analyzed for microbial counts (starter culture and probiotic), pH, titratable acidity, proteolytic activity, syneresis and antioxidant activity. Yogurts containing sesame seeds showed the highest probiotic counts, proteolytic activity, radical scavenging activity high titratable acidity, and low pH. Raw and roasted sesame can selectively impact probiotic growth with limited effect on yogurt starter culture especially at long cold storage (14-28 days). Yogurts enriched with roasted sesame had higher sensory acceptability compared to control and probiotic yogurts. Roasted sesame can be successfully incorporated to improve probiotic viability and sensory properties of stirred yoghurt, as well as to improve the antioxidant properties.

Les artères dites « de résistance » contrôlent les débits sanguins locaux. Elles sont sensibles à la pression qui engendre une contraction myogénique et au débit qui, par l’intermédiaire des forces de cisaillement, stimule l’endothélium et la production d’agents vasorelaxants comme le monoxyde d’azote (NO). Cette balance entre tonus myogénique et dilatation dépendante du flux détermine un tonus basal qui rend plus efficace les systèmes vasoactifs locaux et circulants. Une réactivité qui donne aux artères de résistance la capacité de répondre rapidement aux besoins métaboliques générés par le fonctionnement des organes. Le débit sanguin augmente de façon chronique au cours de la croissance, lors de la grossesse et avec une pratique régulière de l’exercice physique. Le remodelage en réponse à une augmentation chronique de débit sanguin correspond à une augmentation du diamètre, un épaississement de la paroi et une amélioration de la fonction endothéliale de l’artère.

OBJECTIVES:

Nicotine and its associated nicotinic acetylcholine receptors (nAChRs) are believed to be involved in the progression of lung carcinomas. This study aimed at examining the localization of nAChRs in human lung tumours and, by using primary cultures of tumour cells derived from these tumours, determining the nAChR roles in cell proliferation and tumour invasion.
MATERIALS AND METHODS:

Immunohistochemistry was used to assess nAChR expression in non-small cell lung carcinomas (NSCLC). Primary cultures of tumour cells were established from NSCLC tissue samples and the effects of nicotine and nAChR antagonists on cell proliferation and invasion were assessed.
RESULTS:

α5, α7, β2 and β4 nAChR subunits were expressed in all adenocarcinomas (AC) and squamous cell carcinomas (SCC) tissue samples. In AC, all subunits were identified in glandular structures. In SCC, α5, β2 and β4 subunits were essentially identified in tumour cells at invasive fronts, whereas α7 subunit was mainly present in the most differentiated tumour cells and less frequently at invasive fronts. In AC and SCC, there was an inverse distribution of cell proliferation marker Ki-67 and α7 nAChR. Both α7 nAChR and heteromeric nAChRs positively regulated in vitro tumour invasion in NSCLC. Heteromeric nAChRs had a limited activity in regulating tumour cell proliferation in vitro. In contrast, α7 nAChR was a repressor of proliferation in tumour cells isolated from well differentiated NSCLC but mediated the pro-proliferative activity of nicotine in cells isolated from poorly differentiated NSCLC.
CONCLUSION:

α7 nAChR and heteromeric α5*β2*β4* nAChRs play a role in ex vivo tumour progression by stimulating invasion and, depending on the differentiation status of the tumour, by regulating proliferation. Our results suggest that the use of α7 nAChR antagonists to prevent lung cancer progression should be restricted to poorly differentiated tumours.

BACKGROUND:

A chronic increase in blood flow in resistance arteries is associated with increased lumen diameter (outward remodeling) and improved endothelium (NO)-mediated relaxation. Flow-mediated remodeling of resistance arteries is essential for revascularization in ischemic diseases. Nevertheless, it is impaired in 12 to 24-month old rats and in young Zucker Diabetic Fatty (ZDF) rats due to advanced glycation end products (AGEs) and oxidative stress. As type 2 diabetes occurs preferentially in older subjects we investigated flow-mediated remodeling and the effect of the AGEs breaker ALT-711 associated or not to the antioxidant TEMPOL in one-year old lean (LZ) and ZDF rats.
METHODS:

Mesenteric resistance arteries were exposed to high (HF) or normal blood flow (NF) in vivo. They were collected after 2 weeks for in vitro analysis.
RESULTS:

In LZ rats, diameter expansion did not occur despite a significant increase in blood flow in HF arteries. Nevertheless, endothelium-mediated relaxation was higher in HF than in NF arteries. ALT-711, alone or in combination with TEMPOL, restored outward remodeling in HF arteries in association with AGEs reduction. TEMPOL alone had no effect. ALT-711, TEMPOL or the combination of the 2 drugs did not significantly affect endothelium-mediated relaxation in HF and NF arteries.In ZDF rats, diameter did not increase despite the increase in blood flow and endothelium-mediated relaxation was further decreased in HF arteries in association with AGEs accumulation and excessive oxidative stress. In both NF and HF arteries, endothelium-mediated relaxation was lower in ZDF than in LZ rats. ALT-711, TEMPOL or their combination did not improve remodeling (diameter equivalent in HF and NF arteries). In parallel, they did not reduce AGEs level and did not improve MMPs activity. Nevertheless, ALT-711 and TEMPOL partly improved endothelium-mediated relaxation through a reduction of oxidative stress and the association of ALT-711 and TEMPOL fully restored relaxation to the level found in LZ rats.
CONCLUSIONS:

ALT-711 did not improve outward remodeling in mature ZDF rats but it reduced oxidative stress and consequently improved endothelium-dependent relaxation. In mature LZ rats, ALT-711 improved outward remodeling and reduced AGEs level. Consequently, AGEs breaking is differently useful in ageing whether it is associated with diabetes or not.

In resistance arteries, a chronic increase in blood flow induces hypertrophic outward remodeling. This flow-mediated remodeling (FMR) is absent in male rats aged 10 mo and more. As FMR depends on estrogens in 3-mo-old female rats, we hypothesized that it might be preserved in 12-mo-old female rats. Blood flow was increased in vivo in mesenteric resistance arteries after ligation of the side arteries in 3- and 12-mo-old male and female rats. After 2 wk, high-flow (HF) and normal-flow (NF) arteries were isolated for in vitro analysis. Arterial diameter and cross-sectional area increased in HF arteries compared with NF arteries in 3-mo-old male and female rats. In 12-mo-old rats, diameter increased only in female rats. Endothelial nitric oxide synthase expression and endothelium-mediated relaxation were higher in HF arteries than in NF arteries in all groups. ERK1/2 phosphorylation, NADPH oxidase subunit expression levels, and arterial contractility to KCl and to phenylephrine were greater in HF vessels than in NF vessels in 12-mo-old male rats only. Ovariectomy in 12-mo-old female rats induced a similar pattern with an increased contractility without diameter increase in HF arteries. Treatment of 12-mo-old male rats and ovariectomized female rats with hydralazine, the antioxidant tempol, or the angiotensin II type 1 receptor blocker candesartan restored HF remodeling and normalized arterial contractility in HF vessels. Thus, we found that FMR of resistance arteries remains efficient in 12-mo-old female rats compared with age-matched male rats. A balance between estrogens and vascular contractility might preserve FMR in mature female rats.

OBJECTIVE:

Flow- (shear stress-)mediated outward remodeling of resistance arteries is involved in collateral growth during postischemic revascularization. As this remodeling is especially important during pregnancy, we hypothesized that estrogens may be involved. A surgical model eliciting a local increase in blood flow in 1 mesenteric resistance artery was used in 3-month-old ovariectomized female rats either treated with 17-β-estradiol (E2) or left untreated.
METHODS AND RESULTS:

After 14 days, arterial diameter was greater in high-flow arteries than in normal-flow vessels. An ovariectomy suppressed high-flow remodeling, while E2 restored it. High-flow remodeling was absent in mice lacking the estrogen receptor α but not estrogen receptor β. The kinetics of inflammatory marker expression, macrophage infiltration, oxidative stress, and metaloproteinases expression were not altered by the absence of E2 after 2 and 4 days, that is, during remodeling. Nevertheless, E2 was required for the increase in endothelial nitric oxide synthase expression and activation at day 4 when diameter expansion occurs. Finally, the impact of E2 on the endothelium appeared crucial for high-flow remodeling, as this E2 action was abrogated in mice lacking endothelial NOS, as well as in Tie2-Cre(+) ERα(f/f) mice.
CONCLUSIONS:

We demonstrate the essential role of E2 and endothelial estrogen receptor α in flow-mediated remodeling of resistance arteries in vivo.

Shear stress due to blood flow is the most important force stimulating vascular endothelium. Acute stimulation of the endothelium by shear stress induces a vasodilatation mainly due to the release of nitric oxide (NO) among other relaxing agents. After a chronic increase in blood flow (shear stress), the endothelium triggers diameter enlargement, medial hypertrophy and improvement of arterial contractility and endothelium-mediated dilation. Shear stress-mediated outward remodeling requires an initial inflammatory response followed by the production of reactive oxygen species (ROS) and peroxinitrite anions, which activate MMPs and extracellular matrix digestion allowing diameter expansion. This outward remodeling occurs in collateral growth following occlusion of a large artery. In diabetes, an excessive ROS production is associated with the formation of advanced glycation end-products (AGEs) and the glycation of enzymes involved in vascular tone. The balance between inflammation, AGEs and ROS level determines the ability of resistance arteries to develop outward remodeling whereas AGEs and ROS contribute to decrease endothelium-mediated dilation in remodeled vessels. This review explores the interaction between ROS, AGEs and the endothelium in shear stress-mediated outward remodeling of resistance arteries in diabetes. Restoring or maintaining this remodeling is essential for an efficient blood flow in distal organs.

Flow-mediated remodeling of resistance arteries is essential for revascularization in ischemic diseases, but this is impaired in diabetes. We hypothesized that breaking advanced glycation end product (AGE) cross-links could improve remodeling in mesenteric resistance arteries in Zucker diabetic fatty (ZDF) rats compared with lean Zucker (LZ) rats. Arteries, exposed to high (HF) or normal (NF) blood flow after alternate arterial ligation in vivo, were collected after 2 weeks. In LZ rats, HF artery diameter was larger than for NF vessels, but this was not the case in ZDF rats. Endothelium-mediated dilation in ZDF rats, which was lower than in LZ rats, was further decreased in HF arteries. Treatment of rats with the AGE-breaker 4,5-dimethyl-3-phenacylthiazolium chloride (ALT-711) (3 mg/kg/day; 3 weeks) reversed diabetes-induced impairment of HF-dependent remodeling. ALT-711 also improved endothelium nitric oxide-dependent relaxation in mesenteric resistance arteries. Reactive oxygen species reduction restored relaxation in ZDF rats but not in LZ or ALT-711-treated rats. AGEs were reduced in ALT-711-treated ZDF rats compared with ZDF rats. Metalloproteinase activity, necessary for HF-dependent remodeling, was reduced in ZDF rats compared with LZ rats and restored by ALT-711. Thus, targeting AGE cross-links may provide a therapeutic potential for overcoming microvascular complications in ischemic disorders occurring in diabetes.

Heme oxygenase 1 is induced by hemodynamic forces in vascular smooth muscle and endothelial cells. We investigated the involvement of heme oxygenase 1 in flow (shear stress)-dependent remodeling. Two or 14 days after ligation of mesenteric resistance arteries, vessels were isolated. In rats, at 14 days, diameter increased by 23% in high-flow arteries and decreased by 22% in low-flow arteries compared with normal flow vessels. Heme oxygenase activity inhibition using Tin-protoporphyrin abolished diameter enlargement in high-flow arteries and accentuated arterial narrowing in low-flow arteries (32% diameter decrease versus 22% in control). Two days after ligation, heme oxygenase 1 expression increased in high-flow and low-flow vessels, in association with a reduced mitochondrial aconitase activity (marker of oxidative stress) in high-flow arteries only. Inhibition of macrophage infiltration (clodronate) decreased heme oxygenase 1 induction in low-flow but not in high-flow arteries. Similarly, inhibition of NADPH oxidase activity (apocynin) decreased heme oxygenase 1 induction in low-flow but not high-flow arteries. However, dihydroethidium staining was higher in high-flow and low-flow compared with normal flow arteries. In arteries cannulated in an arteriograph, heme oxygenase 1 mRNA increased in a flow-dependent manner and was abolished by N(G)-nitro-l-arginine methyl ester, catalase, or mitochondrial electron transport chain inhibition. Furthermore, heme oxygenase 1 induction using cobalt-protoporphyrin restored altered high-flow remodeling in endothelial NO synthase knockout mice. Thus, in high-flow remodeling, heme oxygenase 1 induction depends on shear stress-generated NO and mitochondria-derived hydrogen peroxide. In low-flow remodeling, heme oxygenase 1 induction requires macrophage infiltration and is mediated by NADPH oxidase-derived superoxide.

BACKGROUND:

Aging is associated with reduced structural and functional adaptation to chronic changes in blood flow (shear stress) in small arteries. As heme oxygenase-1 (HO-1) is induced by hemodynamic forces in vascular smooth muscle and endothelial cells, we hypothesized that it might improve flow-dependent remodeling in aging.
METHOD:

First-order mesenteric arteries from 3 and 16-month-old rats were exposed to high, low, or normal flow by alternate ligation in vivo. Rats were treated with the HO-1 inducer, cobalt protoporphyrin (CoPP, 5 mg/kg) or vehicle. 14 days later, local blood flow was measured in vivo, and arteries were studied in vitro.
RESULTS:

Despite an equivalent change in blood flow, diameter enlargement in the high-flow arteries was blunted in old compared to young rats and was associated with decreased endothelium-dependent relaxation to acetylcholine. In old rats, HO-1 induction with CoPP restored outward remodeling, via a paradoxical reactive oxygen species-dependent mechanism, and was associated with a Mn-superoxide dismutase (SOD) overexpression, as well as a significant reduction of mitochondrial aconitase activity, used as a biomarker for oxidative stress. The heme oxygenase activity inhibitor, Sn-protoporphyrin, and the SOD-mimetic, TEMPOL, prevented the effect of CoPP on remodeling and oxidative status in old rats. Furthermore, HO-1 induction improved endothelial function, in association with increased endothelial nitric oxide synthase protein expression and phosphorylation (Ser-1177). In low-flow arteries, inward remodeling was unaffected by aging or by CoPP. Thus, in old rats, CoPP-induced up-regulation of HO-1 restored high-flow-dependent remodeling (diameter enlargement) and improved endothelial function in mesenteric arteries.
CONCLUSION:

This opens new perspectives in the treatment of ischemic diseases in aging.

Les artères dites « de résistance » contrôlent les débits sanguins locaux. Elles sont sensibles à la pression qui engendre une contraction myogénique et au débit qui, par l’intermédiaire des forces de cisaillement, stimule l’endothélium et la production d’agents vasorelaxants comme le NO. Cette balance entre tonus myogénique et dilatation dépendante du flux détermine un tonus basal qui rend plus efficace les systèmes vasoactifs locaux et circulants. Cette réactivité donne aux artères de résistance la capacité de répondre rapidement aux besoins métaboliques générés par le fonctionnement des organes. Le débit sanguin augmente de façon chronique lors de la croissance, de la grossesse et avec une pratique régulière de l’exercice physique. Une augmentation chronique de débit est également requise dans les zones péri-ischémiques et là le remodelage artériel participe à la revascularisation à côté de l’artériogenèse et de l’angiogenèse. Bien sÛr, un tel remodelage est délétère à proximité de tissus tumoraux. Ce remodelage en réponse à une augmentation chronique de débit sanguin correspond à une augmentation du diamètre, un épaississement de la paroi et une amélioration de la fonction endothéliale de l’artère. Néanmoins, l’amplitude de ce remodelage diminue aussi avec l’âge pour disparaître au-delà de la médiane de l’espérance de vie, à partir de laquelle le risque d’accident cardiovasculaire croit de façon importante. Ce remodelage pourrait représenter une cible thérapeutique potentielle dans le vieillissement vasculaire physiologique aussi bien que pathologique.