Regulation of Inducible Nitric Oxide Synthase (iNOS) and its Potential Role in Insulin Resistance, Diabetes and Heart Failure

Nitric oxide synthases (NOS) are the enzymes responsible for nitric oxide (NO) generation. NO is a reactive oxygen species as well as a reactive nitrogen species. It is a free radical which mediates several biological effects. It is clear that the generation and actions of NO under physiological and pathophysiological conditions are regulated and extend to almost every cell type and function within the circulation. In mammals 3 distinct isoforms of NOS have been identified: neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS). The important isoform in the regulation of insulin resistance (IR) is iNOS. Understanding the molecular mechanisms regulating the iNOS pathway in normal and hyperglycemic conditions would help to explain some of vascular abnormalities observed in type 2 diabetes mellitus (T2DM). Previous studies have reported increased myocardial iNOS activity and expression in heart failure (HF). This review considers the recent animal studies which focus on the understanding of regulation of iNOS activity/expression and the role of iNOS agonists as potential therapeutic agents in treatment of IR, T2DM and HF

Influence of a high-fat diet on cardiac iNOS in female rats

Overexpression of inducible nitric oxide synthase (iNOS) is a key link between high-fat (HF) diet induced obesity and cardiovascular (CV) disease. Several studies have reported that oestradiol has cardioprotective effects that may be mediated through reduction of iNOS activity/expression. In the present study, female Wistar rats were fed a standard diet or a HF diet (balanced diet for laboratory rats enriched with 42% fat) for 10 weeks. Gene and protein expression of iNOS were measured in heart tissue. HF diet-fed rats exhibited a significant increase in cardiac iNOS mRNA by 695% (p<0.05), iNOS protein level by 248% (p<0.01), without changes in nitrate/nitrite levels. Expression of CD36 protein in plasma membranes was increased by 37% (p<0.05), while the concentration of free fatty acids (FFA) was reduced by 25% (p<0.01) in HF diet-fed rats. Expression of the p50 subunit of nuclear factor-κB (NFκB-p50) in heart lysate was increased by 77% (p<0.01) in HF diet-fed rats. Expression and phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinases 1/2 (ERK1/2) in control and HF diet-fed rats were also examined. Expression of Akt and ERK1/2 were unchanged between the groups. There was a significant increase in the ratio of phospho-Akt/total Akt but not for phospho-ERK1/2/total ERK1/2/ in HF-fed rats. Estrogen receptor-α levels (by 50%; p<0.05) and serum oestradiol concentrations (by 35%; p<0.05) were examined and shown to be significantly reduced in HF diet-fed rats. Our results revealed that a HF diet led to increased iNOS expression, most likely via a mechanism involving Akt and NFκB-p50 proteins. Decreased levels of oestradiol and ERα protein in the HF-fed group, in combination with increased iNOS levels are consistent with the hypothesis that oestradiol has a cardioprotective effect through its ability to regulate iNOS expression.PostprintPeer reviewe

Prevalence of the metabolic syndrome in patients with carotid disease according to NHLBI/AHA and IDF criteria: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome (MetS) has been related to type 2 diabetes and cardiovascular diseases. Different criteria for diagnosis of MetS have been recommended, but there is no agreement about which criteria are best to use. The aim of the present study was to investigate agreement between the National Heart, Lung, and Blood Institute, American Heart Association (NHLBI/AHA) and the International Diabetes Federation (IDF) definitions of MetS in patients with symptomatic carotid disease and to compare the frequency of cardiovascular risk factor in patients with MetS diagnosed by these two sets of criteria.</p> <p>Methods</p> <p>The study was a cross-sectional one involving 644 consecutive patients with verified carotid disease who referred to the Vascular Surgery Clinic Dedinje in Belgrade during the period April 2006 - November 2007. Anthropometric parameters blood pressure, fasting plasma glucose and lipoproteins were measured using standard procedures.</p> <p>Results</p> <p>MetS was present in 67.9% of participants, according to IDF criteria, and in 64.9% of participants, according to the NHLBI/AHA criteria. A total of 119 patients were categorized differently by the two definitions. Out of all participants 10.7% had MetS by IDF criteria only and 7.8% of patients had MetS by NHLBI/AHA criteria only. The overall agreement of IDF and NHLBI/AHA criteria was 81.5% (Kappa 0.59, <it>p </it>< 0.001). In comparison with patients who met only IDF criteria, patients who met only NHLBI/AHA criteria had significantly more frequently cardiovascular risk factors with the exception of obesity which was significantly more frequent in patients with MetS diagnosed by IDF criteria.</p> <p>Conclusion</p> <p>The MetS prevalence in patients with symptomatic carotid disease was high regardless of criteria used for its diagnosis. Since some patients with known cardiovascular risk factors were lost by the use of IDF criteria it seems that NHLBI/AHA definition is more suitable for diagnosis of MetS. Large follow-up studies are needed to test prognostic value of these definitions.</p

Treatment of Infected Pseudoaneurysm of Femoral Artery after Vascular Closure Device Deployment: A Practical Solution

Like other invasive procedures, percutaneous coronary interventions are associated with complications. Most common access site for these procedures is common femoral artery. Complications such as groin and retroperitoneal hematoma can be encountered as well as pseudoaneurysms, arteriovenous fistulas, acute arterial occlusion, and infection. When infected pseudoaneurysm occurs, surgical treatment can be extremely difficult. We present a case of the patient in whom infected pseudoaneurysm of common femoral artery developed after percutaneous coronary intervention and was successfully treated by surgical excision and autoarterial graft insertion