G574S affects the transactivation potential of HNF-1alpha on the insulin promoter in pancreatic beta-cells. Although it has been difficult to prove its role in the development of diabetes in case-control association studies, this variant exhibits functional effects consistent with it being a potential diabetes susceptibility allele.
1 The role of the extraendothelial and constitutive isoforms of cyclo-oxygenase-2 (COX-2) in the contractile effect of angiotensin II (Ang II) was investigated using thoracic and abdominal aortic rings without endothelium from young Wistar rats. 2 Ang II elicited similar contractions in both aortic segments, and the effect was inhibited by pretreatment with NS398 (a selective COX-2 inhibitor) but not SC-560 [selective cyclo-oxygenase-1 (COX-1) inhibitor]. 3 COX-2 mRNA was expressed under basal conditions in both aortic segments. Additionally, Ang II increased COX-2 mRNA expression in the abdominal but not the thoracic segment, while cycloheximide (a protein synthesis inhibitor) did not affect the contractile response to Ang II in either of the two segments; this suggests that the effect is not associated with de novo COX-2 synthesis. 4 In conclusion, the basal amount of COX-2 found in aortic smooth muscle cells is sufficient to explain the production of the prostanoids related to the contractile effect of Ang II. The production of these prostanoids, which are derived from constitutive COX-2, occurs independently of the endothelium vascular system.
Background Vascular dysfunction usually preceds clinically detectable fibrosis of systemic sclerosis (SSc). Vascular affection occurs more frequently in limited subtype of SSc (lcSSc) than diffuse subtype (dcSSc). The eNOS catalyses the synthesis of nitricoxide (NO), which maintains basal vascular tone andendothelial function. Abnormal production of e-NOS and/or iNOS impairs NO availability causing disease Objectives To investigate the prevalence of polymorphisms T-786C and G894T of the eNOS gene and the differential expression of eNOS/iNOS in the skin of SSc patients. Methods We included 139 consecutive SSc patients. The genotyping of T-786C and G894T polymorphisms of eNOS gene was performed by Polymerase Chain Reaction Real-Time Assay. The control group comprised 180 age-matched healthy volunteers. For the eNOS/iNOS skin expression we included 31 patients (14 lcSSc and 17 dcSSc). Results Revalence of scleroderma was 53.2% lcSSc (74/139) and46.7% (65/139) dsSSc. In control group: the prevalenceof T-786C polymorphismwas TT 68.45%, TC 29.4%, andCC2.22%;for G894T polymorphism was GG 74.1%, GT 23.02%, TT 2.87%.In lcSSc: T-786Cprevalence was TT 65.5%, TC 30.2% and CC 4.3% (OR 1.8, IC 0.4-7.9 associated to SSc); and the G894T prevalencewas GT 74.3%, GT 20.3% and TT 5.4% (OR 1.94, IC 0.54-7.04 associated to SSc).In dcSSc: the T-786Cprevalence was TT 76.6%, TC 20%, and CC 3.3%, and G894Tpolymorphism was GT 82%, GT 18% and TT 0% without association with SSc.The mean relative expression of eNOS was 10.17±15.5 and iNOS of 7.6±13.05 in lcSSc. For dcSSc the mean relative expression of eNOS was 1.74±1.16 and iNOS of 2.1±2.5. 1.08±0.3 y 1.36±0.7 in skin of volunteers of control group. Conclusions Genetic polymorphisms of eNOS were not arisk forpresenting systemic sclerosis in this sample.In the skin of both subtypes of systemic sclerosis, the relative expression of eNOS and iNOS is increased. However this increase was more meaningful in the lcSSc subtype of the disease. References Kahaleh B. vascular disease in scleroderma: mechanisms of vascular injury. Rheum Dis Clin North Am 2008;34:57-71. A. Dooley, S. Y. Low, A. Holmes, A. G. Kidane, D. J. Abraham, C. M. Black, and K. R. Bruckdorfer Nitric oxide synthase expression and activity in the tight-skin mouse model of fibrosis Rheumatology, 2008; 47: 272 - 280. Disclosure of Interest None Declared
Background Vascular dysfunction usually is observed before clinically detectable fibrosis of systemic sclerosis (SSc). The eNOS catalyses the synthesis of nitric oxide (NO), which maintains basal vascular tone and endothelial function. Abnormal production of e-NOS and/or iNOS impairs NO availability causing vascular disease. Genetic polymorphism may participatein these alterations. Objectives To investigate vascular differences associated to polymorphisms T-786C and G894T of the eNOS gene on differential expression of eNOS/iNOS in the skin and vascular Duplex Sonography parameters of SSc patients. Methods We included 139 consecutive SSc patients. The genotyping of T-786C and G894T polymorphisms of eNOS gene was performed by Polymerase Chain Reaction Real-Time Assay. The control group included 180 age-matched healthy volunteers. For the eNOS/iNOS skin expression we included 31 patients (14 lcSSc and 17 dcSSc). Results In lcSSc: T-786C prevalence was TT65.5%, TC30.2% and CC4.3% (OR 1.8, IC 0.4–7.9 associated to SSc); and the G894T prevalence was GT74.3%, GT20.3% and TT5.4% (OR 1.94, IC 0.54–7.04 associated to SSc). In dcSSc: the T-786C prevalence was TT76.6%, TC20%, and CC3.3%, and G894T polymorphism was GT 82%, GT 18% and TT 0% withoutassociation with SSc. In control group: the prevalence of T-786C polymorphism was TT68.45%, TC29.4%, and CC2.22%; for G894T polymorphismwas GG74.1%, GT23.02%, TT2.87%. The mean relative expression of eNOS was 10.17+/-15.5 and iNOS of 7.6+/-13.05 in lcSSc. For dcSSc the mean relative expression of eNOS was 1.74+/-1.16 and iNOS of 2.1+/-2.5.1.08+/-0.3 and 1.36+/-0.7 in skin of volunteers of control+group. Left brachial intima-media thickness was statistically significantly greater in allelic variants of eNOS in SSc (p=0.025). Conclusions In the skin of both subtypes of systemic sclerosis, the relative expression of eNOS and iNOS is increased. Genetic polymorphisms of eNOS is associated with anormal intima-media thicknes in SSc patients. Disclosure of Interest None Declared
One therapy that has demostrated that it normalize the cardiovascular responses of angiotensin receptor in one experimental model, is the hyperbaric oxygen therapy. It has been described the wide use of dexametasone during the neonatal period of time, having different and controversial responses. Dexametasone has been used commonly due to the improvement in the lung function into the respiratory difficulty syndrome. Some studies reports that the use of steroid during the neonatal period could have some beneficial effects but also it could induce cardiovascular and renal disorder during the development. As it has been described one of the main pathway involved is the renin‐aldosterone‐angiotensin system. Some researchers describe that steroids regulate the angiotensin II receptor and function.Objetivethe main idea is to analize the modification of the expression of angiotensin II receptor in rat with administration neonatal of dexametasone with/without hyperbaric oxygen therapy.Methodologyneonatal rat (2 days) were administrated with dexametasone and were divided in 2 groups one with hyperbaric oxygen therapy and the other without therapy. At the age of 6 weeks the animals were sacrificed, and the expression of the receptor At1 were measured in the heart and the kidney by PCR and inmunohistochemistry.ResultsThe group only with dexametasone showed has major expression of At1 receptor, however the group with dexametasone and hyperbaric oxygen therapy has a reduction in the expression of this receptor.ConclusionThis results could suggest that the hyperbaric oxygen therapy could normalize the expresion in this rats with dexametasone treatment, being beneficial because it could reduce the possibility of one cardiovascular pathology like and infarct.Support or Funding InformationSIP, COFAA, IPNThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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