Current Pharmaceutical Design - Volume 20, Issue 22, 2014

The regulation of endothelial NO synthase (eNOS) employs multiple different cellular control mechanisms impinging on level and activity of the enzyme. This review aims at summarizing the current knowledge on the posttranslational modifications of eNOS, including acylation, nitrosylation, phosphorylation, acetylation, glycosylation and glutathionylation. Sites, mediators and impact on enzyme localization and activity of the Read More

Endothelial nitric oxide synthase (eNOS) is expressed in vascular endothelial cells and plays an important role in the regulation of vascular tone, platelet aggregation and angiogenesis. Protein-protein interactions represent an important posttranslational mechanism for eNOS regulation. eNOS has been shown to interact with a variety of regulatory and structural proteins which provide fine tuneup of eNOS activity and eNOS pro Read More

Numerous epidemiological studies indicate that consumption of polyphenol-rich food and beverages is associated with a protective effect on the cardiovascular system. The beneficial effect has been attributable to several mechanisms including the improvement of the vascular function. Indeed, polyphenols have been shown to be potent stimulators of endothelial vasoprotective mechanisms including the formation of nitri Read More

The methylarginines asymmetric dimethylarginine (ADMA) and monomethylarginine (L-NMMA) are endogenously formed inhibitors of nitric oxide synthases (NOS), which have extensively been investigated as risk markers and used as pharmacological tools to study the L-arginine-nitric oxide (NO) pathway in vitro and in vivo. It is the aim of the present review to summarize the clinical and experimental data on the pharmacolo Read More

Nitric oxide (NO) is a gaseous signaling molecule and effector in various biological processes. In mammalian cells, NO is produced by a family of NO synthases (NOS). Three NOS isoforms have been identified as: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). In addition to NO, NOS also produces superoxide anion. This phenomenon is named NOS uncoupling as superoxide generation mainly occurs when Read More

Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthase (NOS). In the cardiovascular system, endothelial NOS (eNOS) has a major role in maintaining vascular tone and endothelial function, as well as in mediating many other vascular protective properties. Evidence from humans and animals have demonstrated that decreased BH4 bioavailability, with subsequent uncoupling of eNOS, has significant effects Read More

Cardiovascular disease remains the number one killer in the United States and many other countries. Each year, there are enormous research efforts on its pathogenesis, prevention and treatment led by scientists worldwide. One of the most significant research areas is the impact and mechanisms of existing or new cardiovascular risk factors on the vascular system. The current review provides the most updated resear Read More

Many cardiovascular diseases and drug-induced complications are associated with - or even based on - an imbalance between the formation of reactive oxygen and nitrogen species (RONS) and antioxidant enzymes catalyzing the break-down of these harmful oxidants. According to the “kindling radical” hypothesis, the formation of RONS may trigger in certain conditions the activation of additional sources of RONS. Acco Read More

Under physiological conditions, nitric oxide (NO) is produced in the vasculature mainly by the endothelial NO synthase (eNOS). This endothelium-derived NO is a protective molecule with antihypertensive, antithrombotic and anti-atherosclerotic properties. Cardiovascular risk factors such as hypertension, hypercholesterolemia, cigarette smoking and diabetes mellitus induce oxidative stress mostly by stimulation of the NADPH Read More

Response to anti-diabetic medications is not always predictable or favourable even in phenotypically similar type-2 diabetes (T2D) cases. This is not only due to patient’s compliance and access to care but is also considered to be an effect of idiosyncratic differences among individuals, stemming from the combination of their unique genetic background and environmental exposures. In this systematic review, we aimed to summar Read More

It is currently estimated that over 370 million individuals have diabetes, making diabetes a major public health issue contributing significantly to global morbidity and mortality. The steep rise in diabetes prevalence over the past decades is attributable, in a large part, to lifestyle changes, with dietary habits and behaviour as significant contributors. Despite the relatively wide availability of antidiabetic medicine, it is lifestyle appr Read More

The recent increase in the prevalence of obesity seems to be responsible for the increase in T2 Diabetes Mellitus (T2DM). At present around 50 % of T2DM patients are obese and this percentage appears set to increase in the near future. Successful management of T2DM in obese patients is a complicated task, as many parameters such as blood pressure, LDL-cholesterol levels have to be adequately controlled along with HbA1 Read More

Sodium-glucose co-transporters (SGLT2) are mainly expressed in the kidneys and are responsible for the renal handling of glucose load. SGLT2 inhibitors represent the latest oral agents for diabetes treatment. Their unique mechanism of action, which practically spares the insulin secretion or insulin utilization, differentiates the SGLT2 inhibitors from any existing antidiabetic agent. Thus, it is hypothesized that SGLT2 inhibitors Read More

Statins are highly efficacious lipid modifying agents that reduce the risk for cardiovascular (CV) events in both primary and secondary prevention settings. However, statins affect molecular mechanisms which adversely impact on insulin sensitivity and β-cell function, thereby increasing risk for new onset diabetes mellitus (NOD). Defining the mechanisms involved is the focus of considerable current investigation. The statins redu Read More

The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. T2DM is associated with both microvascular (neuropathy, nephropathy and retinopathy) and macrovascular complications [coronary artery disease (CAD), stroke, carotid artery disease and peripheral artery disease (PAD)]. Apart from acting on diabetic dyslipidemia, statins were shown to exert beneficial effects on several diabetic complications as we Read More

Diabetics are regarded a special category of patients known to experience higher rates of cardiovascular complications as compared to the non-diabetic ones. Despite substantial efforts to minimize these risks, with aggressive antiplatelet and lipid lowering therapy, some of the diabetic patients still have a considerable residual risk for cardiovascular adverse events. Important preclinical data with potent lipid-lowering ag Read More

Diabetic neuropathy is a common complication of diabetes mellitus affecting 30-50% of patients and is a major cause for increased costs, morbidity and mortality. Strict diabetes control prevents this complication and may restore neurologic deficits in the early stages. Several efforts have been undertaken to alter the natural history of this complication, including the use of aldose reductase and protein kinase-C inhibitors, as well Read More

The aim of this review is to examine the evidence on the role of antidiabetic agents in patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). In particular, metformin does not seem to have significant effects on liver histology. Glitazones improve steatosis and necro-inflammation, delay progression of fibrosis, and ameliorate glucose and lipid metabolism and subclinical inflammati Read More