Dave Koole1, Joost A van Herwaarden2, Casper G Schalkwijk3, Floris P J G Lafeber4, Aryan Vink5, Mirjam B Smeets6, Gerard Pasterkamp7, Frans L Moll2. 1. Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands; Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: d_koole@yahoo.com. 2. Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands. 3. Department of Internal Medicine, Laboratory for Metabolism and Vascular Medicine, Maastricht University, Maastricht, The Netherlands. 4. Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. 5. Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands. 6. Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands. 7. Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Abstract
BACKGROUND: Diabetes is a risk factor for atherosclerotic disease but negatively associated with the development and progression of abdominal aortic aneurysm (AAA). Advanced glycation end products (AGEs) are increased in diabetes and renders the vascular matrix more resistant to proteolysis. We assessed the concentration of AGEs in AAA biopsies obtained from diabetic and nondiabetic patients and hypothesized that (nonenzymatic) glycation of AAA tissue protects against proteolytic breakdown of collagen. METHODS: AAA biopsies were collected from 30 diabetic and 30 matched nondiabetic AAA patients at the time of open repair. Aortic control samples from 10 nondiabetic and 16 diabetic patients were collected, and concentrations of the AGE cross-link pentosidine was measured. Furthermore, noncross-linking AGEs (adducts), as well as proteolytic enzymes known to play a role in aneurysm development (matrix metalloproteinase [MMP]-2, MMP-9, cathepsin B and S) were quantified. Ex vivo, nondiabetic AAA biopsies were glycated and measured subsequently for collagen type I release. RESULTS: Pentosidine concentrations in AAA wall biopsies were increased in patients with diabetes compared with nondiabetics 9.4 (5.0-13.5) vs 6.0 (2.5-9.6) pmol/μmol lysine (P = .02). Increased pentosidine concentrations were also observed in nonaneurysmatic aortic wall biopsies from diabetic patients. In diabetic AAA vascular wall tissue, pentosidine concentration was negatively correlated with aortic diameter (r = -0.43; P = .02). Ex vivo glycated AAA biopsies were resistant against MMP-induced collagen type I degradation as compared with controls (7.0 vs 10.4 μg/L; P = .02). No differences were observed for AGEs that are not forming cross-links. CONCLUSIONS: These findings suggest that cross-linking AGEs like pentosidine play a protective role in AAA progression in diabetic patients.
BACKGROUND:Diabetes is a risk factor for atherosclerotic disease but negatively associated with the development and progression of abdominal aortic aneurysm (AAA). Advanced glycation end products (AGEs) are increased in diabetes and renders the vascular matrix more resistant to proteolysis. We assessed the concentration of AGEs in AAA biopsies obtained from diabetic and nondiabetic patients and hypothesized that (nonenzymatic) glycation of AAA tissue protects against proteolytic breakdown of collagen. METHODS: AAA biopsies were collected from 30 diabetic and 30 matched nondiabetic AAA patients at the time of open repair. Aortic control samples from 10 nondiabetic and 16 diabeticpatients were collected, and concentrations of the AGE cross-link pentosidine was measured. Furthermore, noncross-linking AGEs (adducts), as well as proteolytic enzymes known to play a role in aneurysm development (matrix metalloproteinase [MMP]-2, MMP-9, cathepsin B and S) were quantified. Ex vivo, nondiabetic AAA biopsies were glycated and measured subsequently for collagen type I release. RESULTS:Pentosidine concentrations in AAA wall biopsies were increased in patients with diabetes compared with nondiabetics 9.4 (5.0-13.5) vs 6.0 (2.5-9.6) pmol/μmol lysine (P = .02). Increased pentosidine concentrations were also observed in nonaneurysmatic aortic wall biopsies from diabeticpatients. In diabetic AAA vascular wall tissue, pentosidine concentration was negatively correlated with aortic diameter (r = -0.43; P = .02). Ex vivo glycated AAA biopsies were resistant against MMP-induced collagen type I degradation as compared with controls (7.0 vs 10.4 μg/L; P = .02). No differences were observed for AGEs that are not forming cross-links. CONCLUSIONS: These findings suggest that cross-linking AGEs like pentosidine play a protective role in AAA progression in diabeticpatients.
Authors: Xuejuan Ning; Ning Ding; Shoshana H Ballew; Caitlin W Hicks; Josef Coresh; Elizabeth Selvin; James Pankow; Weihong Tang; Kunihiro Matsushita Journal: Atherosclerosis Date: 2020-10-06 Impact factor: 5.162
Authors: Matthew J Nordness; B Timothy Baxter; Jon Matsumura; Michael Terrin; Kevin Zhang; Fei Ye; Nancy R Webb; Ronald L Dalman; John A Curci Journal: J Vasc Surg Date: 2021-10-23 Impact factor: 4.860