TY - JOUR
T1 - Hyperglycemia Induces Toll-Like Receptor Activity Through Increased Oxidative Stress
AU - Pahwa, Roma
AU - Jialal, Ishwarlal
PY - 2016/6/1
Y1 - 2016/6/1
N2 - Hyperglycemia-induced oxidative stress and inflammation are central in the genesis of diabetic vascular complications. Toll-like receptors (TLRs) play a crucial role in promoting inflammatory responses and are known to be activated in diabetic patients. Also in animal models, they have been shown to have a role in the pathogenesis of diabetic vasculopathies. However, the mechanisms underlying this increase in TLR activity in diabetes are not well documented. Since increased reactive oxygen species (ROS) are also produced in various tissues under diabetic conditions, we postulated that ROS act as a potential activator of TLR. Several studies support our hypothesis that hyperglycemia-induced oxidative stress appears to be an important factor in promoting TLR activity in monocytes, both microvascular and macrovascular endothelial cells and cardiomyocytes and in animal models. Most importantly, the increase in ROS and TLR activity is ameliorated with antioxidant strategies. Thus, targeting ROS/NADPH oxidase with small molecular inhibitors could be a promising strategy to reduce both oxidative stress and TLR-mediated inflammation in diabetic vascular diseases.
AB - Hyperglycemia-induced oxidative stress and inflammation are central in the genesis of diabetic vascular complications. Toll-like receptors (TLRs) play a crucial role in promoting inflammatory responses and are known to be activated in diabetic patients. Also in animal models, they have been shown to have a role in the pathogenesis of diabetic vasculopathies. However, the mechanisms underlying this increase in TLR activity in diabetes are not well documented. Since increased reactive oxygen species (ROS) are also produced in various tissues under diabetic conditions, we postulated that ROS act as a potential activator of TLR. Several studies support our hypothesis that hyperglycemia-induced oxidative stress appears to be an important factor in promoting TLR activity in monocytes, both microvascular and macrovascular endothelial cells and cardiomyocytes and in animal models. Most importantly, the increase in ROS and TLR activity is ameliorated with antioxidant strategies. Thus, targeting ROS/NADPH oxidase with small molecular inhibitors could be a promising strategy to reduce both oxidative stress and TLR-mediated inflammation in diabetic vascular diseases.
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U2 - 10.1089/met.2016.29006.pah
DO - 10.1089/met.2016.29006.pah
M3 - Review article
C2 - 27105077
AN - SCOPUS:84971265461
VL - 14
SP - 239
EP - 241
JO - Metabolic Syndrome and Related Disorders
JF - Metabolic Syndrome and Related Disorders
SN - 1540-4196
IS - 5
ER -