Angiotensin converting enzyme inhibiting therapy is associated with lower vitreous vascular endothelial growth factor concentrations in patients with proliferative diabetic retinopathy

被引:65
作者
van Buggenum, IMH
Polak, BCP
Reichert-Thoen, JWM
de Vries-Knoppert, WAEJ
van Hinsbergh, VWM
Tangelder, GJ
机构
[1] Vrije Univ Amsterdam, Med Ctr, Inst Cardiovasc Res, Dept Ophthalmol, NL-1007 MB Amsterdam, Netherlands
[2] Vrije Univ Amsterdam, Med Ctr, Inst Cardiovasc Res, Dept Physiol,TNO,PG,Gaubius Lab, NL-1007 MB Amsterdam, Netherlands
关键词
angiotensin-converting enzyme inhibitors; vascular endothelial growth factor; diabetic retinopathy; diabetes mellitus; enalapril; antihypertensive agents; patients;
D O I
10.1007/s00125-001-0747-8
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims/hypothesis. Vascular endothelial growth factor (VEGF) is thought to be instrumental in the progression of diabetic retinopathy. Indications exist that the renin-angiotensin system is involved in VEOF overexpression. We assessed the vitreous VEGF concentrations in patients and related them to anti-hypertensive treatment, with special interest in the use of ACE-inhibitors. Methods. Samples of vitreous fluid (10-80 mul) were obtained from 39 patients both with Type I (insulin-dependent) and Type It (non-insulin-dependent) diabetes mellitus and 11 non-diabetic patients undergoing intra-ocular surgery. The VEGF-A concentrations were assessed by immunoassay. Results. Control patients and patients without proliferative diabetic retinopathy (n = 8) had low and comparable VEGF concentrations (medians < 50 pg/ml). In contrast, patients with proliferative diabetic retinopathy (n = 31) had high vitreous VEGF concentrations (median 1134 pg/ml), which showed a negative correlation with the use of ACE inhibiting medication (Spearman rank-R = -0.54; p = 0.002, n = 13). Diastolic and systolic blood pressure did not differ significantly between the two subgroups with proliferative diabetic retinopathy, i.e. those patients receiving ACE-inhibition (medians 88/160 mm Hg, respectively) and the others (90/160). For the mostly used ACE-inhibitor in the proliferative diabetic retinopathy group, i.e. enalapril (n = 8), a linear dose-effect relation was observed (-20 +/- 4 pg . ml(-1) mg(-1) . day(-1); p = 0.024; coefficient +/- SEM). Conclusion/interpretation. Treatment with ACE-inhibitors attenuates retinal overexpression of VEGF-A in patients with proliferative diabetic retinopathy, probably by interference with a local effect of angiotensin II.
引用
收藏
页码:203 / 209
页数:7
相关论文
共 41 条
[1]   INCREASED VASCULAR ENDOTHELIAL GROWTH-FACTOR LEVELS IN THE VITREOUS OF EYES WITH PROLIFERATIVE DIABETIC-RETINOPATHY [J].
ADAMIS, AP ;
MILLER, JW ;
BERNAL, MT ;
DAMICO, DJ ;
FOLKMAN, J ;
YEO, TK ;
YEO, KT .
AMERICAN JOURNAL OF OPHTHALMOLOGY, 1994, 118 (04) :445-450
[2]  
AFIFI AA, 1996, CHAPMAN HALL TEXTS S, P176
[3]   Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective beta-isoform-selective inhibitor [J].
Aiello, LP ;
Bursell, SE ;
Clermont, A ;
Duh, E ;
Ishii, H ;
Takagi, C ;
Mori, F ;
Ciulla, TA ;
Ways, K ;
Jirousek, M ;
Smith, LEH ;
King, GL .
DIABETES, 1997, 46 (09) :1473-1480
[4]   VASCULAR ENDOTHELIAL GROWTH-FACTOR IN OCULAR FLUID OF PATIENTS WITH DIABETIC-RETINOPATHY AND OTHER RETINAL DISORDERS [J].
AIELLO, LP ;
AVERY, RL ;
ARRIGG, PG ;
KEYT, BA ;
JAMPEL, HD ;
SHAH, ST ;
PASQUALE, LR ;
THIEME, H ;
IWAMOTO, MA ;
PARK, JE ;
NGUYEN, HV ;
AIELLO, LM ;
FERRARA, N ;
KING, GL .
NEW ENGLAND JOURNAL OF MEDICINE, 1994, 331 (22) :1480-1487
[5]  
ALDINGTON SJ, 1995, DIABETOLOGIA, V38, P437, DOI 10.1007/BF00410281
[6]  
Amin RH, 1997, INVEST OPHTH VIS SCI, V38, P36
[7]   RENAL RENIN-ANGIOTENSIN SYSTEM IN DIABETES - FUNCTIONAL, IMMUNOHISTOCHEMICAL, AND MOLECULAR BIOLOGICAL CORRELATIONS [J].
ANDERSON, S ;
JUNG, FF ;
INGELFINGER, JR .
AMERICAN JOURNAL OF PHYSIOLOGY, 1993, 265 (04) :F477-F486
[8]  
BERKA JL, 1995, INVEST OPHTH VIS SCI, V36, P1450
[9]   Role of vascular endothelial growth factor in diabetic nephropathy [J].
Cha, DR ;
Kim, NH ;
Yoon, JW ;
Jo, SK ;
Cho, WC ;
Kim, HK ;
Won, NH .
KIDNEY INTERNATIONAL, 2000, 58 :S104-S112
[10]   Long-term effects of angiotensin-converting enzyme inhibition and metabolic control in hypertensive type 2 diabetic patients [J].
Chan, JCN ;
Ko, GTC ;
Leung, DHY ;
Cheung, RCK ;
Cheung, MYF ;
So, WY ;
Swaminathan, R ;
Nicholls, MG ;
Critchley, JAJH ;
Cockram, CS .
KIDNEY INTERNATIONAL, 2000, 57 (02) :590-600