Taken together, cigarette smoke exposure can aggravate vascular fibrosis and induce eNOS uncoupling in diabetes under experimental condition, suggesting that smoking might exacerbate diabetic vascular impairments.
In conclusion, our results indicated that dopamine D<sub>4</sub> receptor protected against hyperglycemia-induced endothelial dysfunction via the PI3K/eNOS pathway, which may provide a novel strategy in the treatment of diabetes.
Reduced expression of endothelial nitric oxide synthase (eNOS) is a hallmark of endothelial dysfunction in diabetes, which predisposes diabetic patients to numerous cardiovascular complications including blunted angiogenesis.
Diabetes or hypertension-mediated endothelial dysfunction show characteristics such as reduced nitric oxide synthesis through suppression of endothelial nitric oxide synthase activity in endothelial cells, reduced sensitivity of nitric oxide in smooth muscle cells, and inflammation - all of which have been either shown to be directly caused by gene regulatory mechanisms of non-coding RNAs or shown to be having a correlation with them.
Thus, BH<sub>4</sub> is an important mediator of endothelial nitric oxide synthase-dependent responses of cerebral arterioles in diabetes and may have therapeutic potential for the treatment of cerebral vascular disease.
The fibrogenesis of mesangial cells in diabetes was associated with increased superoxide generation and peroxynitrite production via iNOS induction and uncoupling.
In intervention studies using DBA2/J and Nos3 (eNos) KO mouse models of diabetes, TEPP-46 treatment reversed metabolic abnormalities, mitochondrial dysfunction and kidney pathology.
We investigated endothelial nitric oxide synthase involvement on (-)-epicatechin-induced increases in indicators associated with mitochondrial biogenesis in human coronary artery endothelial cells cultured in normal-glucose and high-glucose media, as well as to restore indicators of cardiac mitochondria from the effects of simulated diabetes.
The aim of this study is to quantify global DNA methylation and investigate the relationship with diabetes status and polymorphisms in MTHFR C677T and NOS3G894T genes in mixed ancestry subjects from South Africa.
A NOS3 polymorphism predicts endothelial response to folate in children with diabetes or obesity, with implications for vascular risk and folate intervention studies.
Regarding the eNOSE298D polymorphism, the frequency of the mutant D allele carriage was only observed to be higher among cases with hypertension associated with diabetes and obesity, in comparison with controls, yet not reaching statistical significance (41.2% vs. 34%, p > 0.05).
In stratified analyses, homozygosity for the NOS3 T allele in obese white participants but not in those whose BMI <30 kg/m(2) was associated with an elevated risk of diabetes (OR = 1.47, p = 0.02) when compared to the common GG genotype.
Impaired EDVR was associated significantly with reduced endothelial nitric oxide synthase (eNOS) protein expression in HUVEC (r=0.788, P<0.001), diabetes (P=0.024), and smoking status (yes/no, P=0.047).
To determine the frequency of eNOSG894T variant and to find the possible association between this polymorphism with CAD we studied 207 unrelated patients with total CAD (with and without diabetes) and 92 controls.
Taken together, these results suggest that the combined effects of eNOS deficiency and hyperglycemia contribute to podocyte injury, highlighting the importance of communication between endothelial cells and podocytes in diabetes.
We administered nicorandil to a model of advanced diabetic nephropathy (the streptozotocin-induced diabetes in mice lacking endothelial nitric oxide synthase, eNOSKO); controls included diabetic eNOS KO mice without nicorandil and nondiabetic eNOS KO mice treated with either nicorandil or vehicle.Mice were treated for 8 wk.
Therefore, eNOS gene variation may be a factor in the genetic propensity to T1DM and diabetic retinopathy that may have a prognostic value or may suggest interventional approaches to regulate eNOS in patients with diabetes.
Candidate-gene association studies that examined the association between polymorphisms of endothelial nitric oxide synthase (NOS3) gene (G894T, 4b/a, and T786C) and diabetic nephropathy or diabetes leading to severe nephropathy produced inconclusive results.
Despite the fact that women were older than men (72.3 vs. 69.5 years, p = 0.001) at recruitment, poor long-term survival was not sex-related, but instead predicted by age (p < 0.0001), cardiac failure (p = 0.004), smoking (p = 0.017), diabetes (p = 0.049), and variation in the eNOS gene locus (p = 0.033).
Multivariable linear regression models were used to assess the associations of single NOS3 polymorphisms and haplotypes with ABI after adjustment for covariates (age, sex, body mass index, smoking, total cholesterol, HDL cholesterol, and diabetes).
Enhancement of endothelial nitric oxide synthase production reverses vascular dysfunction and inflammation in the hindlimbs of a rat model of diabetes.
In patients with T2DM, homozygosity for the eNOS Asp298 allele was a significant risk factor (HR 3.12 [1.49-6.56], p = 0.003), but not in subjects without diabetes or hypertension.