- Email: [email protected]
Glycoxidation induces vascular smooth muscle cell injury in diabetes through mediation of membrane attack complement
International Congress Series 1245 (2002) 439 – 440
Glycoxidation induces vascular smooth muscle cell injury in diabetes through mediation of membrane attack complement Noriko Uesugi a,*, Noriyuki Sakata a, Seikoh Horiuchi b, Jing Meng a, Shigeo Takebayashi a a
Second Department of Pathology, School of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0133, Japan b Second Department of Biochemistry, School of Medicine, Kumamoto University, Japan
Abstract Hyperglycemia promotes arteriosclerosis by the enhanced formation of advanced glycation endproducts (AGEs). Increased deposition of AGEs and membrane attack complement (MAC) has been noticed in the vascular wall in human diabetes (DM). In vitro, glycated human CD59 complement regulatory protein, losing MAC inhibitory function. We hypothesize that smooth muscle cell injury is accelerated by the interaction between MAC and glycation of CD59. D 2002 Elsevier Science B.V. All rights reserved. Keywords: Diabetes; Glycoxidation; MAC; Smooth muscle cell injury; Media
1. Aim The purpose of this paper is to investigate the distribution of MAC and AGEs on the medial smooth muscle cells in the renal artery in DM.
2. Method The samples were obtained from 30 autopsy subjects: 16 cases with DM (four with renal dysfunction, five with occasional proteinuria and seven with no renal symptom), 4 cases with hypertension and 11 control cases (17 – 89 years old.). Renal tissue sections *
Corresponding author. Tel.: +81-92-801-1011; fax: +81-92-863-8383. E-mail address: [email protected] (N. Uesugi).
0531-5131/02 D 2002 Elsevier Science B.V. All rights reserved. PII: S 0 5 3 1 - 5 1 3 1 ( 0 2 ) 0 1 0 2 4 - 5
440
N. Uesugi et al. / International Congress Series 1245 (2002) 439–440
were immunohistochemically examined for the expression of MAC, C3 and carboxymethyllysin (CML), CD59 and single-strand DNA for detection of apoptosis and smooth muscle actin (SMA). The percentage of area (%) of MAC and CML deposition in interlobar and arcuate artery was determined using NIH image. The loss of smooth muscle cells (SM) in media is semiquantitatively graded from 0 (none) to 3 (over 50% of loss of SM). Colocalization of SM and CML was assessed using an immunohistochemical double-staining technique.
3. Result In serial sections, CML colocalized with MAC, and both were stained in the area devoid of CD59 expression. Double staining revealed the presence of CML in the area with a loss of SMA. Only a few smooth muscle cells positive for ssDMA were detected among cases. CD59 is weakly positive in media except in the area of loss of SMA. Morphological analysis showed that no relation was observed between intima/ medial ratio and the percent medial deposition of MAC and CML. However, the grade of medial SM loss significantly correlated with the percent medial deposition of CML (r = 0.72) and MAC (r = 0.71). The degree of loss of medial SM was significantly higher in DM cases with renal dysfunction (2 F 0.7) than in DM cases without renal dysfunction (1.0 F 0.9), hypertension (HT) cases (0.7 F 0.6) and elderly patients (0.6 F 0.6, over 60 years old). The percent medial deposition of MAC and CML was significantly higher in DM cases with renal dysfunction (32 F 15%, 18 F 12%) than DM cases with no renal dysfunction (10 F 15%, 4 F 6%), HT cases (6.7 F 8.6, 0.3 F 0.5) and aged patients (4.8 F 6.3%, 0.4 F 1.6%).
4. Conclusion Glycoxidation may promote medial smooth muscle cell necrosis of renal artery in DM patients, which may be mediated by MAC.
Glycoxidation induces vascular smooth muscle cell injury in diabetes through mediation of membrane attack complement Noriko Uesugi a,*, Noriyuki Sakata a, Seikoh Horiuchi b, Jing Meng a, Shigeo Takebayashi a a
Second Department of Pathology, School of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0133, Japan b Second Department of Biochemistry, School of Medicine, Kumamoto University, Japan
Abstract Hyperglycemia promotes arteriosclerosis by the enhanced formation of advanced glycation endproducts (AGEs). Increased deposition of AGEs and membrane attack complement (MAC) has been noticed in the vascular wall in human diabetes (DM). In vitro, glycated human CD59 complement regulatory protein, losing MAC inhibitory function. We hypothesize that smooth muscle cell injury is accelerated by the interaction between MAC and glycation of CD59. D 2002 Elsevier Science B.V. All rights reserved. Keywords: Diabetes; Glycoxidation; MAC; Smooth muscle cell injury; Media
1. Aim The purpose of this paper is to investigate the distribution of MAC and AGEs on the medial smooth muscle cells in the renal artery in DM.
2. Method The samples were obtained from 30 autopsy subjects: 16 cases with DM (four with renal dysfunction, five with occasional proteinuria and seven with no renal symptom), 4 cases with hypertension and 11 control cases (17 – 89 years old.). Renal tissue sections *
Corresponding author. Tel.: +81-92-801-1011; fax: +81-92-863-8383. E-mail address: [email protected] (N. Uesugi).
0531-5131/02 D 2002 Elsevier Science B.V. All rights reserved. PII: S 0 5 3 1 - 5 1 3 1 ( 0 2 ) 0 1 0 2 4 - 5
440
N. Uesugi et al. / International Congress Series 1245 (2002) 439–440
were immunohistochemically examined for the expression of MAC, C3 and carboxymethyllysin (CML), CD59 and single-strand DNA for detection of apoptosis and smooth muscle actin (SMA). The percentage of area (%) of MAC and CML deposition in interlobar and arcuate artery was determined using NIH image. The loss of smooth muscle cells (SM) in media is semiquantitatively graded from 0 (none) to 3 (over 50% of loss of SM). Colocalization of SM and CML was assessed using an immunohistochemical double-staining technique.
3. Result In serial sections, CML colocalized with MAC, and both were stained in the area devoid of CD59 expression. Double staining revealed the presence of CML in the area with a loss of SMA. Only a few smooth muscle cells positive for ssDMA were detected among cases. CD59 is weakly positive in media except in the area of loss of SMA. Morphological analysis showed that no relation was observed between intima/ medial ratio and the percent medial deposition of MAC and CML. However, the grade of medial SM loss significantly correlated with the percent medial deposition of CML (r = 0.72) and MAC (r = 0.71). The degree of loss of medial SM was significantly higher in DM cases with renal dysfunction (2 F 0.7) than in DM cases without renal dysfunction (1.0 F 0.9), hypertension (HT) cases (0.7 F 0.6) and elderly patients (0.6 F 0.6, over 60 years old). The percent medial deposition of MAC and CML was significantly higher in DM cases with renal dysfunction (32 F 15%, 18 F 12%) than DM cases with no renal dysfunction (10 F 15%, 4 F 6%), HT cases (6.7 F 8.6, 0.3 F 0.5) and aged patients (4.8 F 6.3%, 0.4 F 1.6%).
4. Conclusion Glycoxidation may promote medial smooth muscle cell necrosis of renal artery in DM patients, which may be mediated by MAC.