Reduced NO synthesis and eNOS mRNA expression in endothelial cells from newborns with a strong family history of type 2 diabetes

Alvarado-Vásquez, Noé; Zapata, Estrella; Alcázar-Leyva, Susana; Massó, Felipe; Montaño, Luis F.

doi:10.1002/dmrr.743

Cited by 35 publications

(22 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Today, it is recognized that diminished endothelial nitric oxide synthase (eNOS) activity, reduced nitric oxide (NO) synthesis, as well as an increased synthesis of reactive oxygen species (ROS) are characteristics of DM that favor development of pro-atherogenic changes (Tousoulis et al, 2013). Additional evidence supports that endothelial cells from healthy individuals, but with a strong familial history of DM2, show alterations in the synthesis of NO and ROS in presence of high glucose (Alvarado-Vásquez et al, 2007a, 2007b. The latter is probably associated with the numerous changes observed in molecules involved in endothelial functionality (e.g., VCAM-1, vWF), or in the proinflammatory state (e.g., C-reactive protein, TNF-α, E-selectin) (Gogitidze et al, 2010;Gómez et al, 2008;Tousoulis et al, 2013).…”

Section: Endothelial Dysfunction In Diabetes Mellitus (Dm)mentioning

confidence: 95%

Circulating cell-free mitochondrial DNA as the probable inducer of early endothelial dysfunction in the prediabetic patient

Alvarado-Vásquez¹

2015

Experimental Gerontology

Self Cite

View full text Add to dashboard Cite

Section: Endothelial Dysfunction In Diabetes Mellitus (Dm)mentioning

confidence: 95%

Circulating cell-free mitochondrial DNA as the probable inducer of early endothelial dysfunction in the prediabetic patient

Alvarado-Vásquez¹

2015

Experimental Gerontology

Self Cite

View full text Add to dashboard Cite

“…Based on this fact, the question concerning the participation of NO, and the possible altered arginine/NO metabolism in the etiology of insulin resistance and T2DM is raised. T2DM itself is associated with various alterations in the activity and expression of NOS isoenzymes [3][4][5][6]. The advantageous effect of dietary L-arginine, the precursor of NO, on insulin sensitivity, plasma levels of glucose and fatty acids and atherosclerosis has recently been reviewed [7].…”

Section: Introductionmentioning

confidence: 99%

Role of nitric oxide (NO) metabolism and inflammatory mediators in childhood obesity

et al. 2011

View full text Add to dashboard Cite

show abstract

“…The protein may play a compensatory role in this regard. In regenerated and senescent endothelium, the reduced responsiveness to activation of endothelial G i -coupled receptors (27) and the reduced eNOS level (16) reduce the capacity for endothelium-dependent vasodilatation (2,33); (29). The augmented presence of secretoneurin could enhance endotheliumdependent relaxations due to activation or increased expression of the endothelial nitric oxide synthase pathway by non-G idependent mechanisms [e.g., in response to endogenous bradykinin (19)].…”

Section: Discussionmentioning

confidence: 99%

Secretoneurin facilitates endothelium-dependent relaxations in porcine coronary arteries

Chan

Vanhoutte

2011

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Chan CK, Vanhoutte PM. Secretoneurin facilitates endotheliumdependent relaxations in porcine coronary arteries. Am J Physiol Heart Circ Physiol 300: H1159 -H1165, 2011. First published February 4, 2011 doi:10.1152/ajpheart.00519.2010.-Secretoneurin enhances the adhesion and transendothelial migration properties of monocytes and is a part of the peptide family encoded by the secretogranin II gene. The expression of the secretogranin II gene is upregulated in senescent endothelium. The present study was designed to examine the effects of secretoneurin on endotheliumdependent responsiveness. Isometric tension was measured in rings (with or without endothelium) of porcine coronary arteries. Secretoneurin did not induce contraction of quiescent or contracted rings. In preparations contracted by U-46619, relaxation was observed with high concentrations of the peptide. This relaxation was endothelium dependent and reduced by the nitric oxide synthase inhibitor N -nitro-L-arginine methyl ester (L-NAME). It was abolished when the preparations were incubated with L-NAME in combination with the cyclooxygenase inhibitor indomethacin. The relaxation was not affected by the combination of 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34) and 6,12,19,20,25,26-hexahydro-5,27:13,18:21,24-trietheno-11,7-etheno-7H-dibenzo[b,m] [1,5,12,16]tetraazacyclotricosine-5,13-diiumditrifluoroacetate hydrate (UCL 1684), which abrogates endothelium-dependent hyperpolarizations. These results indicate that secretoneurin acutely induces relaxation through the activation of endothelial nitric oxide synthase (eNOS) and cyclooxygenase, with nitric oxide playing the dominant role. Prolonged (24 h) incubation with physiological concentrations of secretoneurin enhanced the relaxations to bradykinin and to the calcium ionophore A-23187, but this difference was not observed in preparations incubated with L-NAME or the calmodulin antagonist calmidazolium. Under these conditions, the relaxation to sodium nitroprusside remained unchanged. Incubation with secretoneurin significantly augmented the expression of eNOS and calmodulin as well as the dimerization of eNOS in cultures of porcine coronary arterial endothelial cells. These observations suggest that secretoneurin not only acutely causes but also, upon prolonged exposure, enhances endotheliumdependent relaxations. nitric oxide; secretogranin II ENDOTHELIUM-DEPENDENT, instantaneous decreases in vascular tone (7a) are mediated by nitric oxide in large arteries in response to increased shear stress and other stimuli. Nitric oxide also prevents smooth muscle proliferation as well as platelet aggregation (32,33). Under normal conditions, endothelium-derived nitric oxide is produced by the endothelial isoform of nitric oxide synthase (eNOS) (1). Endothelial cells also contain cyclooxygenase(s) transforming arachidonic acid into endoperoxides, which are metabolized further into vasoactive prostanoids, in particular, the vasodilator prostacyclin (21).In senescent cultured porcine coronary arterial endot...

show abstract

Reduced NO synthesis and eNOS mRNA expression in endothelial cells from newborns with a strong family history of type 2 diabetes

Abstract: Our results show how HUVECs, isolated from healthy newborns with a strong family history of DM2, have an abnormal intracellular synthesis of NO and an impaired expression of eNOS, GLUT1 and p53 genes, all associated with NO synthesis.

Cited by 35 publications

References 41 publications

Circulating cell-free mitochondrial DNA as the probable inducer of early endothelial dysfunction in the prediabetic patient

Circulating cell-free mitochondrial DNA as the probable inducer of early endothelial dysfunction in the prediabetic patient

Role of nitric oxide (NO) metabolism and inflammatory mediators in childhood obesity

Secretoneurin facilitates endothelium-dependent relaxations in porcine coronary arteries

Contact Info

Product

Resources

About