OBJECTIVE: Coronary atherosclerotic plaque composition of diabetic subjects and localization of receptor for advanced glycation end products (RAGE) and its ligands have not been extensively studied. METHODS AND RESULTS: Hearts from diabetic subjects and age, race, and sex-matched nondiabetic subjects dying suddenly were examined. Coronary arteries were dissected and lesions were evaluated for plaque burden, necrotic core size, and inflammatory infiltrate. The expression of RAGE, the RAGE-binding protein (S100-A12, EN-RAGE), and cell death (apoptosis) were also determined. Lesions from type II diabetic subjects had larger mean necrotic cores (P=0.01) and greater total and distal plaque load (P<0.001) than nondiabetic subjects. Necrotic core size correlated positively with diabetic status, independent of other risk factors. Intimal staining for macrophages, T-cells, and HLA-DR was also significantly greater in diabetic subjects (P=0.03, P=0.003, and P<0.0001), respectively. The association of increased macrophage infiltrate was independent of cholesterol levels and patient age. Expression of RAGE and EN-RAGE was significantly greater in diabetic subjects (P=0.004) and was associated with apoptotic smooth muscle cells and macrophages. CONCLUSIONS: In sudden coronary death, inflammation and necrotic core size play a greater role in the progression of atherosclerosis in diabetic subjects. The expression of RAGE and EN-RAGE may further compromise cell survival and promote plaque destabilization.
OBJECTIVE: Coronary atherosclerotic plaque composition of diabetic subjects and localization of receptor for advanced glycation end products (RAGE) and its ligands have not been extensively studied. METHODS AND RESULTS: Hearts from diabetic subjects and age, race, and sex-matched nondiabetic subjects dying suddenly were examined. Coronary arteries were dissected and lesions were evaluated for plaque burden, necrotic core size, and inflammatory infiltrate. The expression of RAGE, the RAGE-binding protein (S100-A12, EN-RAGE), and cell death (apoptosis) were also determined. Lesions from type II diabetic subjects had larger mean necrotic cores (P=0.01) and greater total and distal plaque load (P<0.001) than nondiabetic subjects. Necrotic core size correlated positively with diabetic status, independent of other risk factors. Intimal staining for macrophages, T-cells, and HLA-DR was also significantly greater in diabetic subjects (P=0.03, P=0.003, and P<0.0001), respectively. The association of increased macrophage infiltrate was independent of cholesterol levels and patient age. Expression of RAGE and EN-RAGE was significantly greater in diabetic subjects (P=0.004) and was associated with apoptotic smooth muscle cells and macrophages. CONCLUSIONS: In sudden coronary death, inflammation and necrotic core size play a greater role in the progression of atherosclerosis in diabetic subjects. The expression of RAGE and EN-RAGE may further compromise cell survival and promote plaque destabilization.
Authors: Steven Rosenberg; Michael R Elashoff; Philip Beineke; Susan E Daniels; James A Wingrove; Whittemore G Tingley; Philip T Sager; Amy J Sehnert; May Yau; William E Kraus; L Kristin Newby; Robert S Schwartz; Szilard Voros; Stephen G Ellis; Naeem Tahirkheli; Ron Waksman; John McPherson; Alexandra Lansky; Mary E Winn; Nicholas J Schork; Eric J Topol Journal: Ann Intern Med Date: 2010-10-05 Impact factor: 25.391
Authors: Jenny E Kanter; Farah Kramer; Shelley Barnhart; Michelle M Averill; Anuradha Vivekanandan-Giri; Thad Vickery; Lei O Li; Lev Becker; Wei Yuan; Alan Chait; Kathleen R Braun; Susan Potter-Perigo; Srinath Sanda; Thomas N Wight; Subramaniam Pennathur; Charles N Serhan; Jay W Heinecke; Rosalind A Coleman; Karin E Bornfeldt Journal: Proc Natl Acad Sci U S A Date: 2012-01-17 Impact factor: 11.205
Authors: Julie A Lovshin; Petter Bjornstad; Leif E Lovblom; Johnny-Wei Bai; Yuliya Lytvyn; Geneviève Boulet; Mohammed A Farooqi; Sam Santiago; Andrej Orszag; Daniel Scarr; Alanna Weisman; Hillary A Keenan; Michael H Brent; Narinder Paul; Vera Bril; Bruce A Perkins; David Z I Cherney Journal: Diabetes Care Date: 2018-10-01 Impact factor: 19.112
Authors: Petter Bjornstad; Pattara Wiromrat; Richard J Johnson; Rachel Sippl; David Z I Cherney; Randy Wong; Marian J Rewers; Janet K Snell-Bergeon Journal: Diabetes Care Date: 2018-11-27 Impact factor: 19.112
Authors: Stanley Chia; O Christopher Raffel; Masamichi Takano; Guillermo J Tearney; Brett E Bouma; Ik-Kyung Jang Journal: Diabetes Res Clin Pract Date: 2008-05-05 Impact factor: 5.602
Authors: Ling Yan; Per Bjork; Radu Butuc; Joseph Gawdzik; Judy Earley; Gene Kim; Marion A Hofmann Bowman Journal: Atherosclerosis Date: 2013-02-28 Impact factor: 5.162
Authors: Ryo Kawakami; Shunsuke Katsuki; Richard Travers; Dayanna Carolina Romero; Dakota Becker-Greene; Livia Silva Araujo Passos; Hideyuki Higashi; Mark C Blaser; Galina K Sukhova; Josef Buttigieg; David Kopriva; Ann Marie Schmidt; Daniel G Anderson; Sasha A Singh; Luis Cardoso; Sheldon Weinbaum; Peter Libby; Masanori Aikawa; Kevin Croce; Elena Aikawa Journal: Arterioscler Thromb Vasc Biol Date: 2020-05-28 Impact factor: 8.311