Adiponectin, in contrast to leptin, is not associated with body mass index, waist circumference and HOMA-IR in subjects of a west-African population.

Factors associated with plasma levels of adiponectin and leptin were studied in adult subjects without diabetes from Cotonou in Benin (West-Africa). Seventy (70) men and 45 women were included in the study. Anthropometric variables were measured and a venous blood sample was drawn from each subject, after an overnight fasting period, for measurement of plasma glucose, insulin, leptin, and adiponectin levels. HOMA-IR was determined to assess insulin resistance. Adiponectin and leptin levels were higher in women than in men (with adiponectin 18.48 ± 12.77 vs.7.8 ± 10.39 µg/mL, P < 0.0001, and leptin 30.77 ± 19.16 vs. 8.66 ± 8.24 ng/mL, P < 0.0001). Fasting insulin level and HOMA-IR were also higher in the females. Hyperleptinemia was observed in 66,96% of subjects and hypoadiponectinemia was present in 44.35% of subjects. In both men and women, leptin correlated with age (r = 0.2; P = 0.02), BMI (r = 0.572; P < 0.0001), waist circumference (r = 0.534; P < 0.0001), fasting insulin (r = 0.461; P < 0.001), and HOMA-IR (r = 0.430; P < 0.0001). No significant correlation was observed for adiponectin levels with these variables. Only in women, adiponectin was inversely correlated with fasting glucose (r = -0.423; P < 0.004). These data confirm previous descriptions of leptin but suggest that variations in factors determining serum adiponectin levels observed between ethnicities could also been seen between populations from the same ethnicity.

Polykystose renale autosomique dominante (PKAD) au CNHU-HKM de Cotonou: profil épidémiologique, clinique, biologique et intérêt du dépistage familial

Introduction: Étudier le profil épidémiologique, clinique et paraclinique de la PKAD chez des patients diagnostiqués au CNHU de Cotonou et évaluer l'intérêt d'un dépistage chez les patients à risque. Méthodes: Il s'agit d'une étude transversale comportant une revue de dossiers des patients cliniquement diagnostiqués PKAD à la clinique universitaire de néphrologie et d'hémodialyse du 1er janvier 2000 au 31 janvier 2011, et une enquête familiale chez les patients où le diagnostic de PKAD a été confirmé entre le 1er février et le 31 Août 2011.Un séquençage à la recherche de mutations dans les gènes de la Polycystine 1 et 2 a été réalisé chez les cas index. Résultats: L'incidence hospitalière de la PKAD était de 7,8 cas par an. Le dépistage familial avait permis d'examiner 99 membres de 22 familles et de confirmer 14 cas de PKAD. L'âge moyen des patients était de 45,6±12,8ans. Le signe physique le plus fréquent était l'hypertension artérielle (HTA (83%). Une insuffisance rénale chronique était observée dans 75% des cas. Le séquençage direct avait permis de mettre en évidence 7 nouvelles mutations dont 02 mutations dans les gènes PKD2 et 5 dans PKD1. Conclusion: La PKAD relativement fréquente, présente de nouvelles mutations chez les patients diagnostiqués au CNHU de Cotonou. Le conseil génétique est particulièrement indiqué dans les familles où la maladie rénale a débuté précocement

Decreased vascular contractility induced by hemin is associated with a reduced rho-kinase activity.

OBJECTIVES: In this study, the role of rho-kinase activity in the modulation of vascular contractility induced by hemin, a heme oxygenase inducer, was investigated. METHODS: Aortic rings from Wistar rats were incubated in physiological saline solution (PSS) containing hemin at 10-(4) M for six hours then contracted with phenylephrine, and a dose-response curve was established. The effect of Y-27632, a rho-kinase inhibitor, on the relaxation of the pre-contracted aortic rings was then studied. RESULTS: Incubation of the aortic rings in hemin induced an increased expression of heme oxygenase 1 (HO-1). A reduction in the contractile force of aortic rings incubated in hemin was observed in response to phenylephrine. Y-27632 at a concentration of 10-(6) M induced a 36% relaxation of the control aortic rings but only a 20% relaxation in aortic rings treated with hemin. CONCLUSION: These data suggest that the decreased vascular contractility induced by hemin could, in part, result from an inhibition of rho-kinase activity.

Hemin, a carbon monoxide donor, improves systemic vascular compliance by inhibiting the RhoA-Rhokinase pathway in spontaneous hypertensive rats.

Carbon monoxide donors have nitrite oxide vasorelaxant properties. We performed this study in order to determine the impact of Hemin on smooth muscle layer vasoreactivity in spontaneous hypertensive rats as compared to control Wistar rats. Twenty-one days of peritoneal administration of Hemin decreased the mean arterial blood pressure in spontaneous hypertensive rats (150+/-5 mmHg in spontaneous hypertensive rats treated with Hemin=30 vs. 166+/-6 mmHg in spontaneous control n=30, P<0.05). The passive relaxation of isolated aortic rings after the initial stretch was more important in spontaneous hypertensive treated with Hemin as compared to spontaneous hypertensive treated by Hemin and decreased the maximal contractile force induced by phenylephrine in Wistar aortic rings (C, n=10; H, n=10) although EC(50) values remained unchanged. In spontaneous hypertensive rats, contractile force was impaired in control rats and increased slightly with Hemin treatment. Global potassium channels were decreased in spontaneous hypertensive rats treated with Hemin and this decrease was predominant on Kv channels sensitive current attested by a patch clamp and confirmed by a reduced Kv 1.5 protein expression. On the other hand, the relaxation of the precontracted aortic ring induced by Y27632, an inhibitor of Rhokinase activity, was altered with Hemin. In Wistar rats, the magnitude of relaxation by Y27632 at 310(-7)M was 30% in Hemin-treated rats and 40% in control rats (P>0.05), when expressed as the amplitude of the 80 mM KCl-solution-induced contraction. At the same concentration, the relaxation induced by Y27632 was 115% in spontaneous hypertensive rats -C and 90% in spontaneous hypertensive rats -H (P<0.05). Moreover, western blotting showed that Hemin treatment decreased the amount of the active form of GTP-RhoA but the total RhoA remained unchanged.

Electrophysiological maturation of rat mesenchymal stem cells after induction of vascular smooth muscle cell differentiation in vitro.

Previous studies have suggested that mesenchymal stem cells (MSCs) can differentiate into smooth muscle-like cells. However their functionalities remain questionable. The aim of this study was to investigate the functionality of MSCs differentiated into smooth muscle (SM) in vitro by SM-inducing medium. MSCs have been isolated from rat bone marrow and cultured in SM-inducing medium. After 21 days in culture, messenger RNA and specific SM proteins such as myosin heavy chain and myosin light chain 2 were expressed in the in vitro differentiated MSCs to a similar level of that in freshly isolated SM cells (SMCs). At the electrophysiological level, MSCs presented an outward K+ current with an IK(DR) component and IK(Ca) component. In vitro differentiation induced an enhancement of the IK(Ca) current to a level similar to that observed in aortic SMCs. Calcium homeostasis measurements revealed that both differentiated and undifferentiated MSCs responded to extracellular adenosine triphosphate (ATP) in a similar fashion to SMCs. However MSCs failed to contract in response to ATP. This data shows that despite specific SM protein expression and modification of electrophysiological properties similar to that of aortic SMCs, MSCs cultured in differentiation medium failed to display contractile properties. These results underline the necessity to find the ideal cultured conditions to induce complete SMC function.

Undifferentiated mesenchymal stem cells seeded on a vascular prosthesis contribute to the restoration of a physiologic vascular wall.

BACKGROUND: We evaluated the possibility of restoring a physiologic vascular wall using undifferentiated mesenchymal stem cells (MSCs) seeded on a polyurethane vascular prosthesis. METHODS: Undifferentiated MSCs were seeded on a vascular prosthesis and implanted into Wistar male rats (weight, 350 g) to investigate differentiation into smooth muscle cells and to determine graft endothelialization in vivo. RESULTS: Seeded or nonseeded grafts were surgically implanted. Undifferentiated MSCs were first labelled for green fluorescent protein. After 2 weeks in vivo, MSC that were initially self-expanded on the graft in a monolayer were organized in a multicellular layer mimicking media of aortic adjacent wall. They coexpressed green fluorescent protein and smooth muscle proteins that were not present before the in vivo engraftment, indicating that in vivo conditions induced smooth muscle protein maturation. Undifferentiated MSC showed an electrophysiologic profile quite different than mature smooth muscle cells. In both in vitro- and in vivo-differentiated MSCs, adenosine triphosphate, an IP(3)-dependent agonist, induced an increase in calcium similar to that which occurred in mature smooth muscle cells. However, MSCs failed to respond to caffeine, a ryanodine receptor activator, indicating the absence of mature calcium signaling, and finally, contraction was absent. Endothelialization attested by immunohistology and scanning electron microscopy was greater in MSC-seeded grafts that prevent thrombosis. CONCLUSION: Only partial smooth muscle cell differentiation of MSCs resulted when seeded on vascular grafts, but MSCs spontaneously restore a media-like thick wall. Mesenchymal stem cells have a positive impact on in vivo endothelialization in rats that supports their potential for use in vascular surgery. CLINICAL RELEVANCE: Thrombosis of vascular prostheses is a major complication of surgery. We showed on rat aorta that mesenchymal stem cells seeded on polyurethane patch restore endothelium. It also induced incomplete smooth muscle differentiation. In the future, stem cell could prevent thrombosis of vascular prostheses.

Increase in serum adiponectin concentration in patients with heart failure and cachexia: relationship with leptin, other cytokines, and B-type natriuretic peptide.

AIMS: Adiponectin is a fat-derived hormone involved in the regulation of metabolism. Adiponectin concentration is inversely related to body weight and, in animals, causes weight loss. We, therefore, measured adiponectin concentration in patients with heart failure (HF) and cachexia. METHODS AND RESULTS: Serum adiponectin concentrations were measured in three groups of patients with coronary artery disease (CAD): (i) HF, reduced left ventricular systolic function, and cachexia (n = 10); (ii) HF, reduced systolic function but no cachexia (n = 20); (iii) HF-controls-patients with CAD, no HF, and preserved systolic function (n = 10); and in a healthy control group (n = 7). Patients with HF and cachexia had higher concentrations of adiponectin [23.8 (10.2-37.2) microg/mL] than all other groups: HF-no cachexia 8.1 (0.5-16.6) microg/mL; CAD-controls 7.1 (0.4-13.5) microg/mL; and healthy controls 8.7 (2.5-16.8) microg/mL) (P < 0.05 for each comparison). Adiponectin correlated negatively with body mass index, percentage of body fat, waist circumference and insulin resistance, and positively with B-type natriuretic peptide (BNP) and tumour necrosis factor-alpha. CONCLUSION: Cachexia in HF is associated with an increase in adiponectin concentration. This may represent preservation of the physiological response to change in body fat but might also suggest that adiponectin plays a role in the pathogenesis of cachexia. The correlation between BNP and adiponectin also raises the possibility that the former might increase the secretion of the latter.

Effets du clenbutérol sur l'expression de l'IGF-1 et des IGFPBs par les cellules musculaires C2C12

Nous avons etudie les effets du clenbuterol; un agoniste du recepteur ?2-adrenergique entrainant l'hypertrophie musculaire; sur l'expression de l'IGF-1 et des IGFBPs par les myotubes de cellules C2C12 en culture. A la concentration de 10-4 M; le clenbuterol a entraine une augmentation du niveau de l'ARN messager de l'IGF-1; IGFBP-4 et de l'IGFBP-5. L'effet sur l'IGFBP-5 est apparu apres 24h alors que les effets sur l'IGF-1 et l'IGFBP-4; plus tardifs; ont ete observes au bout de 48 heures d'incubation. Ces resultats montrent que le clenbuterol agit directement sur les cellules musculaires pour augmenter de l'expression de l'IGF-1 et des IGFBPs; mediateurs possibles de l'hypertrophie musculaire

Role of IGF-I and IGFBPs in the changes of mass and phenotype induced in rat soleus muscle by clenbuterol.

Clenbuterol induces hypertrophy and a slow-to-fast phenotype change in skeletal muscle, but the signaling mechanisms remain unclear. We hypothesized that clenbuterol could act via local expression of insulin-like growth factor I (IGF-I). Administration of clenbuterol to 3-mo-old female Wistar rats resulted in a 10 and 13% increase of soleus muscle mass after 3 and 9 days, respectively, reaching 16% after 4 wk. When associated with triiodothyronine, clenbuterol induced a dramatic slow-to-fast phenotype change. In parallel, clenbuterol administration induced in soleus muscle a fivefold increase in IGF-I mRNA levels associated with an eightfold increase in IGF-binding protein (IGFBP)-4 and a fivefold increase of IGFBP-5 mRNA levels on day 3. This increased IGF-I gene expression was associated with an increase in muscle IGF-I content, already detected on day 1 and persisting until day 5 without increase in serum IGF-I concentrations. These data show that muscle hypertrophy induced by clenbuterol is associated with a local increase in muscle IGF-I content. They suggest that clenbuterol-induced muscle hypertrophy could be mediated by local production of IGF-I.