Biomedical subjects

Georgia Soldatos

Publications and source records attributed to Georgia Soldatos.

3 recordsLinked to original sources

PubMed2006

Advanced glycation end products and vascular structure and function.

Diabetes mellitus has now reached epidemic proportions in the Western world. The associated microvascular and macrovascular complications are a result of severe metabolic derangement, which leads to chronic tissue injury. Although there are a number of proposed pathophysiologic mechanisms for the vascular complications associated with diabetes, this review focuses predominantly on the role of advanced glycation end products (AGEs) in the pathogenesis of diabetes-associated atherosclerosis. The potential role of AGEs in enhancing arterial stiffness, an entity occurring with a greater prevalence in populations known to have higher-than-normal AGE levels, is also examined. Pharmacologic interventions aimed at reducing the level of these chemical compounds or interrupting their action provide hope for the future treatment of both atherosclerotic vascular disease and systolic hypertension, particularly in the setting of diabetes.

Animals↗

PubMed2005

Advanced-glycation end products in insulin-resistant states.

Insulin resistance is a central component of a number of clinical conditions, including the metabolic syndrome, diabetes, and hypertension. There is emerging evidence that the consequent hyperinsulinemia and visceral adiposity may be directly responsible for the excess cardiovascular morbidity and mortality seen in these conditions. Advanced-glycation end products, a chemically diverse group of compounds found in higher levels in insulin-resistant states, have also been shown to adversely affect endothelial function as well as activate numerous intracellular signaling pathways implicated in the atherosclerotic pathway. In this review, we summarize the factors thought to be important in both the initiation and exacerbation of the insulin-resistant state, and directly examine the potential role of advanced-glycation end products in this process.

Adipose Tissue↗

PubMed2005

Below the radar: advanced glycation end products that detour "around the side". Is HbA1c not an accurate enough predictor of long term progression and glycaemic control in diabetes?

Advanced glycation is the irreversible attachment of reducing sugars onto the free amino groups of proteins. Its physiological roles are thought to include the identification of senescent proteins and hence there is a time dependent accumulation of advanced glycation end products (AGEs). AGE labelled proteins are catabolised by cells into low molecular weight peptides and amino acids and excreted primarily via the kidneys. This process appears to be tightly controlled by AGE clearance receptor complexes containing AGE-R1, AGE-R2 and AGE-R3 and scavenger receptors such as CD36, SR-AII and SR-BI. Conditions such as diabetes, however, which have a metabolic overload of reducing sugars, rapidly accelerate AGE formation. In addition, advanced glycation is facilitated by oxidative stress and renal disease even in the absence of increases in reducing sugar concentrations. As part of our western diet, we also ingest AGEs of which approximately 50-80% are absorbed, catabolised and excreted over a period of two days. As AGE levels rise during diabetes, interruption of normal function occurs via three distinct mechanisms, namely AGE induced cross-linking of extracellular matrices, stiffening elastic fibres, disturbing cellular adhesion and preventing turnover. The second is by intracellular formation of AGEs, which causes generalised cellular dysfunction. The third is via the chronic activation of specific receptors such as RAGE, the receptor for advanced glycation end products, which produces excesses in inflammatory molecule production. Due to the range of dysfunction produced by the accumulation of AGEs in diabetes, there is a growing need for early recognition and intervention in this process.

Journal Article↗