Protein Block Stops Vascular Damage in Diabetes
By HospiMedica International staff writers Posted on 24 Jun 2013 |
A new study demonstrates that the inhibition of a protein activated when blood sugar is raised suppresses accelerated atherosclerosis in diabetic mice.
Researchers at Lund University (Sweden) conducted a study in Streptozotocin (STZ)-induced diabetic in mice to investigate whether Nuclear Factor of Activated T-Cells (NFAT) activation may be a link between diabetes and atherogenesis, by measuring blood monocytes, endothelial activation, and inflammatory markers in the aorta, and proinflammatory cytokines in plasma. The study was initiated following previous studies that showed that hyperglycemia activates the transcription factor NFAT in the arterial wall, inducing the expression of the pro-atherosclerotic protein osteopontin.
The study showed that NFAT activation resulted in 2.2 fold increase in aortic atherosclerosis and enhanced proinflammatory burden. Subsequent in vivo treatment with the NFAT blocker A-285222 for four weeks completely inhibited the diabetes-induced aggravation of atherosclerosis, while having no effect in nondiabetic mice. The STZ-treated mice also exhibited hyperglycemia and higher plasma cholesterol and triglycerides, but these were unaffected by A-285222. In fact, the substance did not affect NFAT in any other cells or organs, ruling out systemic immunosuppression as the mechanism behind reduced atherosclerosis. The study was published in the June 3, 2013, issue of PLOS one.
“That is important. We don’t want to suppress the whole immune system. We also saw that the substance only has an effect when NFAT is active. The plaque formation was only stopped in diabetic mice and not in nondiabetic mice, which had normal blood sugar levels”, said lead author Anna Zetterqvist, MSc. “It appears that there are different mechanisms behind plaque formation caused by diabetes and not caused by diabetes.”
A wealth of epidemiologic evidence demonstrate that hyperglycemia promotes a widespread and aggressive form of atherosclerosis in the coronary arteries, lower extremities, and extracranial carotid arteries of diabetic patients, causing nearly 80% of all deaths and much of their disability. Both diabetes type 1 and type 2 are independent risk factors for myocardial infarction (MI), peripheral vascular disease (PVD), and stroke. In addition, recent studies also show a causal association between elevated glucose levels and increased carotid intima-media thickness, a marker of subclinical atherosclerosis.
Related Links:
Lund University
Researchers at Lund University (Sweden) conducted a study in Streptozotocin (STZ)-induced diabetic in mice to investigate whether Nuclear Factor of Activated T-Cells (NFAT) activation may be a link between diabetes and atherogenesis, by measuring blood monocytes, endothelial activation, and inflammatory markers in the aorta, and proinflammatory cytokines in plasma. The study was initiated following previous studies that showed that hyperglycemia activates the transcription factor NFAT in the arterial wall, inducing the expression of the pro-atherosclerotic protein osteopontin.
The study showed that NFAT activation resulted in 2.2 fold increase in aortic atherosclerosis and enhanced proinflammatory burden. Subsequent in vivo treatment with the NFAT blocker A-285222 for four weeks completely inhibited the diabetes-induced aggravation of atherosclerosis, while having no effect in nondiabetic mice. The STZ-treated mice also exhibited hyperglycemia and higher plasma cholesterol and triglycerides, but these were unaffected by A-285222. In fact, the substance did not affect NFAT in any other cells or organs, ruling out systemic immunosuppression as the mechanism behind reduced atherosclerosis. The study was published in the June 3, 2013, issue of PLOS one.
“That is important. We don’t want to suppress the whole immune system. We also saw that the substance only has an effect when NFAT is active. The plaque formation was only stopped in diabetic mice and not in nondiabetic mice, which had normal blood sugar levels”, said lead author Anna Zetterqvist, MSc. “It appears that there are different mechanisms behind plaque formation caused by diabetes and not caused by diabetes.”
A wealth of epidemiologic evidence demonstrate that hyperglycemia promotes a widespread and aggressive form of atherosclerosis in the coronary arteries, lower extremities, and extracranial carotid arteries of diabetic patients, causing nearly 80% of all deaths and much of their disability. Both diabetes type 1 and type 2 are independent risk factors for myocardial infarction (MI), peripheral vascular disease (PVD), and stroke. In addition, recent studies also show a causal association between elevated glucose levels and increased carotid intima-media thickness, a marker of subclinical atherosclerosis.
Related Links:
Lund University
Latest Critical Care News
- Powerful AI Risk Assessment Tool Predicts Outcomes in Heart Failure Patients
- Peptide-Based Hydrogels Repair Damaged Organs and Tissues On-The-Spot
- One-Hour Endoscopic Procedure Could Eliminate Need for Insulin for Type 2 Diabetes
- AI Can Prioritize Emergecny Department Patients Requiring Urgent Treatment
- AI to Improve Diagnosis of Atrial Fibrillation
- Stretchable Microneedles to Help In Accurate Tracking of Abnormalities and Identifying Rapid Treatment
- Machine Learning Tool Identifies Rare, Undiagnosed Immune Disorders from Patient EHRs
- On-Skin Wearable Bioelectronic Device Paves Way for Intelligent Implants
- First-Of-Its-Kind Dissolvable Stent to Improve Outcomes for Patients with Severe PAD
- AI Brain-Age Estimation Technology Uses EEG Scans to Screen for Degenerative Diseases
- Wheeze-Counting Wearable Device Monitors Patient's Breathing In Real Time
- Wearable Multiplex Biosensors Could Revolutionize COPD Management
- New Low-Energy Defibrillation Method Controls Cardiac Arrhythmias
- New Machine Learning Models Help Predict Heart Disease Risk in Women
- Deep-Learning Model Predicts Arrhythmia 30 Minutes before Onset
- Breakthrough Technology Combines Detection and Treatment of Nerve-Related Disorders in Single Procedure