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AGE/RAGE signaling

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Rap1a Activity Elevated The Impact Of Endogenous Ages In Diabetic Collagen To Stimulate Increased Myofibroblast Transition And Oxidative Stress, Stephanie D. Burr, Christopher C. Dorroh, James A. Stewart May 2022

Rap1a Activity Elevated The Impact Of Endogenous Ages In Diabetic Collagen To Stimulate Increased Myofibroblast Transition And Oxidative Stress, Stephanie D. Burr, Christopher C. Dorroh, James A. Stewart

Faculty and Student Publications

Diabetics have an increased risk for heart failure due to cardiac fibroblast functional changes occurring as a result of AGE/RAGE signaling. Advanced glycation end products (AGEs) levels are higher in diabetics and stimulate elevated RAGE (receptor for AGE) signaling. AGE/RAGE signaling can alter the expression of proteins linked to extracellular matrix (ECM) remodeling and oxidative stressors. Our lab has identified a small GTPase, Rap1a, that may overlap the AGE/RAGE signaling pathway. We sought to determine the role Rap1a plays in mediating AGE/RAGE changes and to assess the impact of isolated collagen on further altering these changes. Primary cardiac fibroblasts from …


Rap1a Regulates Cardiac Fibroblast Contraction Of 3d Diabetic Collagen Matrices By Increased Activation Of The Age/Rage Cascade, Stephanie D. Burr, James A. Stewart Jun 2021

Rap1a Regulates Cardiac Fibroblast Contraction Of 3d Diabetic Collagen Matrices By Increased Activation Of The Age/Rage Cascade, Stephanie D. Burr, James A. Stewart

Faculty and Student Publications

Cardiovascular disease is a common diabetic complication that can arise when cardiac fibroblasts transition into myofibroblasts. Myofibroblast transition can be induced by advanced glycated end products (AGEs) present in the extracellular matrix (ECM) activating RAGE (receptor for advanced glycated end products) to elicit intracellular signaling. The levels of AGEs are higher under diabetic conditions due to the hyperglycemic conditions present in diabetics. AGE/RAGE signaling has been shown to alter protein expression and ROS production in cardiac fibroblasts, resulting in changes in cellular function, such as migration and contraction. Recently, a small GTPase, Rap1a, has been identified to overlap the AGE/RAGE …


Extracellular Matrix Components Isolated From Diabetic Mice Alter Cardiac Fibroblast Function Through The Age/Rage Signaling Cascade, Stephanie D. Burr, James A. Stewart Jun 2020

Extracellular Matrix Components Isolated From Diabetic Mice Alter Cardiac Fibroblast Function Through The Age/Rage Signaling Cascade, Stephanie D. Burr, James A. Stewart

Faculty and Student Publications

© 2020 The Authors Individuals suffering from diabetes have an increased risk of developing cardiovascular complications such as heart failure. Heart failure can be a result of the stiffening of the left ventricle, which occurs when cardiac fibroblasts become “active” and begin to remodel the extracellular matrix (ECM). Fibroblast “activation” can be triggered by the AGE/RAGE signaling cascade. Advanced Glycation End products (AGEs) are produced and accumulate in the ECM over time in a healthy individual, but under hyperglycemic conditions, this process is accelerated. In this study, we investigated how the presence of AGEs in either non-diabetic or diabetic ECM …