Role of Ligands of Receptor for Advanced Glycation End Products (RAGE) in Peripheral Artery Disease

2018 ◽  
Vol 21 (5) ◽  
pp. 456-463 ◽  
Author(s):  
Sho-ichi Yamagishi ◽  
Takanori Matsui
2014 ◽  
Vol 34 (4) ◽  
pp. 933-938 ◽  
Author(s):  
Lisanne C. de Vos ◽  
Douwe J. Mulder ◽  
Andries J. Smit ◽  
Robin P.F. Dullaart ◽  
Nanne Kleefstra ◽  
...  

Objective— Advanced glycation end products play a pivotal role in atherosclerosis. Recently, we showed that tissue advanced glycation end products deposition, noninvasively assessed by skin autofluorescence (SAF), is increased in patients with peripheral artery disease. The aim of the present study was to establish whether SAF is associated with all-cause mortality and with fatal or nonfatal major adverse cardiovascular events (MACE) in patients with peripheral artery disease. Approach and Results— We performed a single-center prospective cohort study of 252 patients with peripheral artery disease (mean age, 66 ± 11 years), recruited from the outpatient clinic (October 2007 to June 2008) who were followed until June 2013. SAF was measured with the AGE Reader. The primary end point was all-cause mortality, and the secondary end point was fatal or nonfatal MACE, defined as cardiovascular death and nonfatal myocardial infarction or stroke. During a median follow-up of 5.1 (interquartile range, 5.0–5.3) years, 62 (25%) patients died. Fatal or nonfatal MACE occurred in 62 (25%) patients. A higher SAF was associated with increased risk for all-cause mortality (hazard ratio per unit increase, 2.01; 95% confidence interval, 1.40–2.88; P =0.0002) and fatal or nonfatal MACE (hazard ratio, 1.82; 95% confidence interval, 1.28–2.60; P =0.001), also after adjustment for cardiovascular risk factors and the use of lipid-lowering drugs (hazard ratio, 1.63; 95% confidence interval, 1.13–2.34; P =0.009 and hazard ratio, 1.50; 95% confidence interval, 1.04–2.17; P =0.03, for all-cause mortality and fatal and nonfatal MACE, respectively). Conclusions— SAF as a measure of advanced glycation end products deposition is independently associated with all-cause mortality and fatal or nonfatal MACE in patients with peripheral artery disease after a 5-year follow-up.


2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Lynne L. Johnson ◽  
Jordan Johnson ◽  
Rebecca Ober ◽  
April Holland ◽  
Geping Zhang ◽  
...  

Background Expression of receptor for advanced glycation end products (RAGE) plays an important role in diabetic peripheral artery disease. We proposed to show that treatment with an antibody blocking RAGE would improve hind limb perfusion and muscle viability in diabetic pig with femoral artery (FA) ligation. Methods and Results Purpose‐bred diabetic Yucatan minipigs with average fasting blood sugar of 357 mg/dL on insulin to maintain a glucose range of 300 to 500 mg/dL were treated with either a humanized monoclonal anti‐RAGE antibody (CR‐3) or nonimmune IgG. All pigs underwent intravascular occlusion of the anterior FA. Animals underwent ( 201 Tl) single‐photon emission computed tomography/x‐ray computed tomography imaging on days 1 and 28 after FA occlusion, angiogenesis imaging with [ 99m Tc]dodecane tetra‐acetic acid–polyethylene glycol–single chain vascular endothelial growth factor (scVEGF), muscle biopsies on day 7, and contrast angiogram day 28. Results showed greater increases in perfusion to the gastrocnemius from day 1 to day 28 in CR‐3 compared with IgG treated pigs ( P =0.0024), greater uptake of [99mTc]dodecane tetra‐acetic acid‐polyethylene glycol‐scVEGF (scV/Tc) in the proximal gastrocnemius at day 7, confirmed by tissue staining for capillaries and vascular endothelial growth factor A, and less muscle loss and fibrosis at day 28. Contrast angiograms showed better reconstitution of the distal FA from collaterals in the CR‐3 versus IgG treated diabetic pigs ( P =0.01). The gastrocnemius on nonoccluded limb at necropsy had higher 201 Tl uptake (percentage injected dose per gram) and reduced RAGE staining in arterioles in CR‐3 treated compared with IgG treated animals ( P =0.04). Conclusions A novel RAGE‐blocking antibody improved hind limb perfusion and angiogenesis in diabetic pigs with FA occlusion. Contributing factors are increased collaterals and reduced vascular RAGE expression. CR‐3 shows promise for clinical treatment in diabetic peripheral artery disease.


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