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Etienne Larger

Publications and source records attributed to Etienne Larger.

10 recordsLinked to original sources
PubMed2006

Angiotensinogen impairs angiogenesis in the chick chorioallantoic membrane.

Angiotensinogen shares with other members of the serine protease inhibitor (serpin) family antiangiogenic properties. Angiotensinogen inhibits in vitro endothelial cell proliferation, and is antiangiogenic in ovo in the chick chorioallantoic membrane assay. The cellular mode of action of angiotensinogen has been studied by applying purified human angiotensinogen or Chinese hamster ovary cells producing recombinant angiotensinogen onto the developing chorioallantoic membrane. Vessel density of the control and angiotensinogen-treated areas was quantitated by using Sambucus nigra lectin, a specific endothelial cell marker. After 48 h of angiotensinogen treatment by either applying purified angiotensinogen or angiotensinogen-producing Chinese hamster ovary cells, there was a 70% decrease in mesodermic vessel density in comparison to the control sections. Angiotensinogen treatment induced a strong decrease in endothelial cell proliferation of the chorioallantoic membrane vasculature, as shown by incorporation of bromo-deoxyuridine. Two days after local angiotensinogen treatment, increased apoptosis of endothelial cells of mesodermal blood vessels was detected by transferase-mediated deoxyuridine triphosphate nick end labeling assay. As assessed by in situ hybridization, the gene expression pattern of the main vascular growth factors and their receptors was not altered by angiotensinogen. Angiotensinogen, therefore, impairs angiogenesis without altering the expression level of vascular growth factors through the induction of apoptosis and decreased endothelial cell proliferation.

Angiogenesis Inhibitors↗
PubMed2006

Angiotensinogen modulates renal vasculature growth.

We have shown previously that angiotensinogen, like other members of the serine protease inhibitor family, has antiangiogenic properties in vitro on cultured endothelial cells and in ovo in the chick chorioallantoic membrane assay. The aim of this study was to show the effects of angiotensinogen on vascular wall remodeling in vivo. We measured the vessel wall thickness (tunica media) stained with an antibody to alpha-actin. In the kidney, arterioles were 21.5% thinner in male transgenic mice overexpressing human angiotensinogen than in male control animals. In other vascular beds, the arterial wall thickness was not affected. By using in situ hybridization and Northern blot analysis, human angiotensinogen expression was detected at a high level in the male kidney and at a much lower level in other organs. There is a relationship between the effect of angiotensinogen on arterial wall thickness and the local expression level of angiotensinogen in this model of transgenic mice. Because human angiotensinogen is not cleaved to a significant extent by mouse renin, the reduction in kidney arterial wall thickness is because of angiotensinogen itself and not angiotensin II, and we show that the reduction was not because of hypoplasia or hypotropia. In contrast, a marked difference in the expression of platelet-derived growth factor receptor-beta was observed in the kidney arterioles at day 5 when compared with controls. Altogether, these observations provide the first quantitative evidence that a high level of angiotensinogen expression can inhibit the growth of kidney artery walls in vivo.

Angiotensinogen↗
PubMed2006

Comparison of nutritional consequences of conventional therapy of obesity, adjustable gastric banding, and gastric bypass.

BACKGROUND: Roux-en-Y gastric bypass (RYGBP) is more efficient than adjustable gastric banding (AGB) in weight loss and relieving co-morbidities, but nutritional complications of each surgical procedure have been poorly evaluated. METHODS: A cross-sectional study was performed to compare nutritional parameters in 201 consecutive obese patients, who had been treated either by conventional behavioral and dietary therapy (CT, n=110) or by bariatric surgery, including 51 AGB and 40 RYGBP. RESULTS: BMI was similar after AGB (36.6 +/- 5.3 kg/m2) and RYGBP (35.4 +/- 6.3 kg/m2), but patients in the RYGBP group had lost more weight and had less metabolic disturbances than those in the AGB group. On the other hand, the prevalence of nutritional deficits was significantly higher in the RYGBP group than in the 2 other groups (P<0.01), whereas the AGB group did not differ from CT. Particularly, the RYGBP group presented an unexpected high frequency of deficiencies in fat-soluble vitamins. Moreover, vitamin B12, hemoglobin, plasma prealbumin and creatinine concentrations were low in the RYGBP group. CONCLUSION: RYGBP is more efficient than AGB in correcting obesity, but this operation is associated with a higher frequency of nutritional deficits that should be carefully monitored.

Adult↗
PubMed2005

Large genomic rearrangements in the hepatocyte nuclear factor-1beta (TCF2) gene are the most frequent cause of maturity-onset diabetes of the young type 5.

Maturity-onset diabetes of the young (MODY) 5 is caused by mutations in the TCF2 gene encoding the transcription factor hepatocyte nuclear factor-1beta. However, in 60% of the patients with a phenotype suggesting MODY5, no point mutation is detected in TCF2. We have hypothesized that large genomic rearrangements of TCF2 that are missed by conventional screening methods may account for this observation. In 40 unrelated patients presenting with MODY5 phenotype, TCF2 was screened for mutations by sequencing. Patients without mutations were then screened for TCF2 rearrangements by the quantitative multiplex PCR of short fluorescent fragments (QMPSF). Among the 40 patients, the overall detection rate was 70%: 18 had point mutations, 9 had whole-gene deletions, and 1 had a deletion of a single exon. Similar phenotypes were observed in patients with mutations and in subjects with large deletions. These results suggest that MODY5 is more prevalent than previously reported, with one-third of the cases resulting from large deletions of TCF2. Because QMPSF is more rapid and cost effective than sequencing, we propose that patients whose phenotype is consistent with MODY5 should be screened first with the QMPSF assay. In addition, other MODY genes should be screened for large genomic rearrangements.

Adolescent↗
PubMed2005

Role of beta-cells in type 1 diabetes pathogenesis.

Whether autoimmunity results primarily from a defect of the immune system, target organ dysfunction, or both remains an open issue in most human autoimmune diseases. The highly multigenic background on which diabetes develops in the NOD mouse and in the human suggests that numerous gene variants associate in contributing to activation of autoimmunity to beta-cells. Both immune genes and islet-related genes are involved. The presence of beta-cells is required for initiation of diabetes autoimmunity to proceed. Available experiments in the NOD mouse and epidemiological evidence in the human point to proinsulin as a key autoantigen in diabetes. The functional importance of insulin, the high number of autoantigens characterized at different stages of diabetes, and their clustering within beta-cell subparticles point to the islet as a starting point in the initiation phase of the disease. Genes that direct the autoimmune reaction toward the beta-cell target, autoantigens that are recognized by autoreactive B- and T-cells along the autoimmune process, the importance of beta-cells in the activation of autoreactive lymphocytes, and the expression level of key beta-cell molecules along diabetes development are successively considered in this review.

Animals↗
PubMed2004

Role of the renin-angiotensin system in primitive erythropoiesis in the chick embryo.

Inactivation of the gene encoding mouse angiotensin I-converting enzyme (ACE), which converts angiotensin I into angiotensin II, results in anemia in adult animals. This anemia is corrected by angiotensin II, demonstrating the involvement of angiotensin II in adult (definitive) erythropoiesis. We investigated the possible role of the renin-angiotensin system (RAS) in primitive erythropoiesis in the yolk sac of the chicken embryo. Enzymatically active ACE was detected in the yolk sac endoderm, concomitantly with the differentiation of blood islands in the adjacent yolk sac mesoderm. The simultaneous presence of all the other components of the RAS (renin, angiotensinogen, angiotensin II receptor) in the vicinity of the blood islands suggests that this system is involved in erythropoiesis. This role was confirmed by in vivo blockade of the RAS with fosinoprilate, a specific inhibitor of chicken ACE, which decreased hematocrit by 15%. A similar decrease in hematocrit was observed following treatment with the angiotensin II receptor antagonist Sar1-Ile8-Angiotensin II, suggesting that this effect was mediated by angiotensin II. Both treatments affected hematocrit by decreasing erythroblast proliferation. Thus, the RAS, and its effector peptide angiotensin II in particular, modulates primitive erythropoiesis.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Hyperglycemia-induced defects in angiogenesis in the chicken chorioallantoic membrane model.

Diabetes is associated with abnormal angiogenesis. Increased angiogenesis contributes to severe forms of diabetic retinopathy, but angiogenesis is decreased in response to myocardial ischemia in diabetic patients. We evaluated the direct effect of hyperglycemia on angiogenesis in the chicken chorioallantoic membrane assay, a model of active neoangiogenesis. Hyperglycemia, lasting up to 7 days, was induced in 7-day-old chick embryos by a single intravitellus glucose injection. Control embryos received either water (volumic control) or mannitol (osmotic control). Hyperglycemia decreased angiogenesis in this model from the 5th day on. The pattern and expression level of the main vascular growth factors' genes were not altered by hyperglycemia, as assessed by in situ hybridization and semiquantitative RT-PCR. As early as 2 days after hyperglycemia was induced, an increased apoptosis of endothelial cells and pericytes was detected by transferase-mediated deoxyuridine triphosphate nick-end labeling assay and electron microscopy. In the meantime, endothelial cell proliferation was decreased, as assessed by incorporation of bromo-deoxyuridine. Hyperglycemia can therefore impair angiogenesis without altering the expression level of vascular growth factors through induction of apoptosis and decreased proliferation of endothelial cells.

Allantois↗
PubMedDate not supplied

Normal renal function 8 to 13 years after cyclosporin A therapy in 285 diabetic patients.

BACKGROUND: Cyclosporin A (CyA) may induce acute nephrotoxicity. The question has been raised of the possible long-term unfavorable course of CyA-induced lesions. Advantage was taken of a large cohort of diabetic patients treated for several months using moderate CyA dosage to evaluate the long-term evolution of renal function in such patients. METHODS: Two hundred and eighty five recently diagnosed type 1 diabetic patients having received CyA for a mean of 19.9 months were monitored for 13 years, in parallel with 100 similar patients treated with insulin alone. RESULTS: In the CyA-treated group, a transient increase in creatininemia levels occurred during the first 18 months of treatment associated with a transient increase in renal vascular resistance. Both effects disappeared later on: creatininemia levels then remained normal. Inulin and p-aminohippurate (PAH) clearances remained normal throughout follow-up. Neither permanent renal failure nor progressive deterioration of renal function occurred in either group or in individual patients. A 10 to 12% increase in inulin and PAH clearance was elicited by IV amino acid infusion at 7 to 10 years, a finding consistent with a normal renal functional reserve. Patients with moderate kidney lesions on biopsy at 1 year had normal and stable clearance values at 7 to 13 years. The prevalence of arterial hypertension and retinopathy was lower in the CyA-treated group than in the control group, possibly because of the tighter metabolic control obtained in the CyA group. CONCLUSION: These results suggest that low-dose CyA treatment combined with thorough monitoring does not result in long-term renal dysfunction.

Adult↗
PubMedDate not supplied

[Hyperglycemia and angiogenesis].

Vascular complications of chronic hyperglycemia cause most of diabetes-associated morbidity and mortality. Main targets of chronic hyperglycemia are vascular endothelial cells. Ischemia is the late consequence of vascular damage in patients with diabetes and triggers an angiogenic response. In patients with diabetes, the angiogenic response to chronic ischemia can be excessive in some of the target organs and insufficient in others, in the same individual. The direct effects of hyperglycemia on the expression level of vascular growth factors have been variably appreciated and depend on the studied organ and model. Beyond the described effects of hyperglycemia on the expression level of vascular growth factors, direct and indirect effects of hyperglycemia on endothelial cell proliferation, extra-cellular matrix and metalloproteases might be involved in the pathology of angiogenesis in diabetes.

Cell Division↗