Expertos Invitados





CONTRIBUIÇAO DA PREDISPOSIÇAO A HIPERTENSAO ARTERIAL PARA A SUSCETIBILIDADE A NEFROPATIA DIABETICA

(especial para SIIC © Derechos reservados)
Alterações na regulação do ciclo celular e na produção de matriz extracelular podem estar envolvidas na maior suscetibilidade à nefropatia diabética em indivíduos com predisposição à HA.
butori9.jpg Autor:
B lopes de faria j
Columnista Experto de SIIC
Artículos publicados por B lopes de faria j
Recepción del artículo
17 de Febrero, 2004 		Primera edición
14 de Mayo, 2004 		Segunda edición, ampliada y corregida
7 de Junio, 2021

CONTRIBUIÇAO DA PREDISPOSIÇAO A HIPERTENSAO ARTERIAL PARA A SUSCETIBILIDADE A NEFROPATIA DIABETICA

Resumen
A nefropatia diabética (ND) acomete cerca de 35% dos pacientes portadores de diabetes mellitus (DM). Várias linhas de evidências sugerem que a predisposição à hipertensão arterial (HA) aumenta o risco de desenvolvimento da ND. Com o objetivo de entender os mecanismos celulares e moleculares envolvidos na interação entre predisposição à HA e suscetibilidade a ND nosso grupo tem estudado ratos espontaneamente hipertensos (SHR) com DM induzido por estreptozotocina. Esses ratos que se tornam hipertensos em 100% dos casos com 12 semanas de idade são normotensos com 4 a 6 semanas de vida. Portanto, nesta fase é possível se estudar a influência da genética da hipertensão independente da presença do fenótipo, HA. Nosso grupo demonstrou que os ratos SHR pré-hipertensão apresentam redução renal de fibronectina e aumento na velocidade de replicação das células mesangiais, alterações que não foram observadas nos controles geneticamente normtensos ratos Wistar Kyoto (WKY). Após indução do DM, observamos redução significativa da replicação de células renais acompanhada de aumento de um inibidor do ciclo celular o p27Kip1 e da produção de uma proteína pró-fibrótica, a fibronectina. Essas alterações que puderam ser revertidas com o tratamento anti-hipertensivo e estão envolvidas na patogênese da ND não estavam presentes nos ratos WKY diabéticos. Essas observações sugerem que alterações na regulação do ciclo celular e na produção de matriz extracelular podem estar envolvidas na maior suscetibilidade à ND em indivíduos com predisposição à HA.

Palabras clave
Nefropatia diabética, hipertensão arterial, ciclo celular, SHR, fibronectina


Artículo completo
(castellano)
Extensión:  +/-5.1 páginas impresas en papel A4
Exclusivo para suscriptores/assinantes

CONTRIBUTION OF PREDISPOSITION OF HYPERTENSION TO SUSCEPTIBILITY TO DIABETIC NEPHROPATHY

Abstract
It is unclear why only a subset of patients with diabetes mellitus (DM) develops diabetic nephropathy. Several lines of evidences suggest that predisposition to hypertension is involved in susceptibility to diabetic renal disease. Spontaneously hypertensive rats (SHR) extensively studied as animal model of essential hypertension are normotensive during the first 4 to 6 weeks of age and 100% of the rats will develop hypertension with 12 weeks of age. If these rats are studied with 4 to 6 weeks of age we can investigate the effects of the genetic of hypertension independently of that determined by hypertension per se. We have demonstrated that in pre-hypertensive SHR renal expression of fibronectin is decreased and mesangial cell proliferation rate is increased when compared to the genetically normotensive control, Wistar Kyoto (WKY) rats. Two weeks after the induction of diabetes SHR rats presented significant reduction in renal cell replication with elevation of a cell cycle inhibitor, p27Kip1. These abnormalities that have been involved in the pathogenesis of diabetic nephropathy were not present in the diabetic WKY rats. In addition, renal fibronectin expression was elevated only in the diabetic SHR. These abnormalities could be prevented in the diabetic SHR by antihypertensive treatment. In conclusion, these observations could contribute to understanding the mechanism involved in susceptibility to diabetic renal disease in individuals with predisposition to hypertension and orientates intervention aimed at prevention of diabetic nephropathy.

Key words
Diabetic nephropathy, hypertension, cell cycle, SHR, fibronectin

Clasificación en siicsalud
Artículos originales > Expertos de Iberoamérica >
página   www.siicsalud.com/des/expertocompleto.php/

Especialidades
Principal: Nefrología y Medio Interno
Relacionadas: Diagnóstico por Laboratorio, Endocrinología y Metabolismo, Genética Humana



Comprar este artículo
Extensión: 5.1 páginas impresas en papel A4

file05.gif (1491 bytes) Artículos seleccionados para su compra



Bibliografía del artículo
  1. US Renal Data System (USRDS) 2001: Annual Data Report: Atlas of End-Stage Renal Disease in the United States. Bethesda, NIH, National Institute of Diabetes and Digestive and Kidney Diseases, 2001.
  2. Raine AEG: Epidemiology, development and treatment of end-stage renal failure in type 2 (non-insulin-dependent) diabetic patients in Europe. Diabetologia 1993; 36:1099-1104.
  3. Trivedi HS, Pang MMH, Campbell A, Saab P: Slowing the progression of chronic renal failure: Economic benefits and patients' perspectives. Am J Kidney Dis 2002; 39:721–729.
  4. Lopes de Faria JB, Bittencourt ZZLC, Ribeiro Alves MAVF: Prevalência da nefropatia diabética em pacientes adultos com insuficiência renal crônica terminal. Rev Ass Med Bras 1995; 41:353-356.
  5. World Health Organization. The World Health Report 1997.
  6. Borch-Johnsen K, Andersen PK, Deckert T: The effect of proteinuria on relative mortality in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 1985; 28: 590-596.
  7. The Diabetes Control and Complications Trial Research Group: The effect of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329:977-986.
  8. UK Prospective Diabetes Study (UKPDS) Group: Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352:837-853.
  9. Seaquist ER, Goetz FC, Rich S, Barbosa J: Familial clustering of diabetic kidney disease. Evidence for genetic susceptibility to diabetic nephropathy. N Engl J Med 1989; 320:1161-1165.
  10. Pettitt DJ, Saad MF, Bennett PH, Nelson RG, Knowler WC: Familial predisposition to renal disease in two generations of Pima Indians with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 1990; 33:438-443.
  11. Canani LH, Gerchman F, Gross JL: Increased familial history of arterial hypertension, coronary heart disease, and renal disease in Brazilian type 2 diabetic patients with diabetic nephropathy. Diabetes Care 1998; 21:1545-1550.
  12. Viberti GC, Keen H, Wiseman MJ: Raised arterial pressure in parents of proteinuric insulin-dependent diabetics. Br Med J 1987; 295:515-517.
  13. Krolewski AS, Canessa M, Warran JH, Laffel LMB, Christlieb AR, Knowler WC, Rand LI: Predisposition to hypertension and susceptibility to renal disease in insulin-dependent diabetes mellitus. N Engl J Med 1988; 318:140-145.
  14. Lopes de Faria JB, Friedman R, Tariq T, Viberti GC: Prevalence of raised sodium-lithium countertransport activity in type 1 diabetic patients. Kidney Int 1992; 41: 877-882.
  15. Canessa M, Adragna N, Solomon H, Connolly TM, Tosteson BS, Tosteson DC: Increased sodium-lithium countertransport in red cell of patients with essential hypertension. N Engl J Med 1980; 302:772-776.
  16. Hasstedt SJ, Wu LL, Ash KO, Kuida H, Williams RR: Hypertension and sodium-lithium countertransport in Utah pedigrees: evidences for major-locus inheritance. Am J Hum Genet 1988; 43:14-22.
  17. Monciotti CG, Semplicini A, Morocutti A, Maioli M, Cipollina MR, Barzon I, Palaro C, Brocco E, Trevisan M, Fioretto P, Crepaldi G, Nosadini R: Elevated sodium-lithium countertransport activity in erythrocytes is predictive of the development of microalbuminuria in IDDM. Diabetologia 1997; 40:654-661.
  18. Cooper ME, Allen TJ, O'Brien RC, Macnullan PA, Clarke B, Jerums G, Doyle AE: Effects of genetic hypertension on diabetic nephropathy in the rat: functional and structural characteristics. J Hypertens 1988; 6:1009-1016.
  19. Okamoto K, Tabei R, Fukushima M, Nosaka S, Yamori Y, Ichijima K,Haebara H, Matsumoto M, Maruyama T, Suziki Y, Tamegai IM: Further observations of the development of a strain of spontaneously hypertensive rats. Jap Circ J 1966; 30:703-716.
  20. Lopes de Faria JB, Zoukhri D, Lorenzi M: Mesangial cells abnormalities in spontaneously hypertensive rats before the onset of hypertension. Kidney Int 1997; 52:387-392.
  21. Lopes de Faria JB, Silveira LA: Increased renal cell proliferation in spontaneously hypertensive rats before the onset of hypertension. Nephron 2002; 91:170-172.
  22. Jones SC, Saunders HJ, Qi W, Pollock CA: Intermittent high glucose enhances cell growth and collagen synthesis in cultured human tubulointerstitial cells. Diabetologia 1999; 42:1113-1119.
  23. Righetti AE, Boer-Lima PA, Lopes de Faria JB: The presence of genetic hypertension stimulates early renal accumulation of fibronectin in experimental diabetes mellitus. Diabetologia 2001; 44:2088-2091.
  24. Pavan MV, Ghini B, Castro M, Lopes de Faria JB: Prevention of hypertension attenuates albuminuria and renal expression of fibronectin in diabetic spontaneously hypertensive rats. Am J Nephrol 2003; 23:422-428.
  25. Lehfeld L, Ghini B, Silveira LA, Lopes de Faria JB: Early blood pressure normalization independent of the class of antihypertensive agent prevents augmented renal fibronectin and albuminuria in experimental diabetic nephropathy. Kidney Blood Press Res (in presss).
  26. Al-Douahji M, Brugarolas J, Brown PAJ, Stehman-Breen CO, Alpers CE, Shankland SJ: The cyclin kinase inhibitor p21WAF1/CIP1 is required for glomerular hypertrophy in experimental diabetic nephropathy. Kidney Int 1999; 56:1691-1699.
  27. Mogensen CE, Andersen MJF, Denmark A: Increased kidney size and glomerular filtration rate in early juvenile diabetes. Diabetes 1973; 22:706-712.
  28. Wolf G, Schroeder R, Thaiss F, Ziyadeh FN, Helmchen U, Stahl RAK: Glomerular expression of p27Kip1 in diabetic db/db mouse: role of hyperglycemia. Kidney Int 1998; 53:869-879.
  29. Silveira LA, Bacchi CE, Pinto GA, Lopes de Faria JB: The genetics of hypertension modifies response in renal cell replication induced by experimental diabetes. Diabetes 2002; 51:1529-1534.
  30. Ziyadeh FN, Hoffman BB, Han DC, Iglesias-de la Cruz MC, Hong SW, Isono M, Chen S, McGowan TA, Sharma K: Long-term prevention of renal insufficiency, excess matrix gene expression, and glomerular mesangial metrix expansion by treatment with monoclonal antibody in db/db diabetic mice. PNAS 2000; 97:8015-8020.
  31. Awazu M, Omori S, Ishikura K, Hida M, Fujita H: The lack of cyclin kinase inhibitor p27Kip1 ameliorates progression of diabetic nephropathy: J Am Soc Nephrol 2003; 14:699-708.
Título español
Resumen
 Palabras clave
 Bibliografía
 Artículo completo
(exclusivo a suscriptores)
 Autoevaluación
  Tema principal en SIIC Data Bases
 Especialidades

 English title
 Abstract
 Key words
Full text
(exclusivo a suscriptores)

Autor 
Artículos
Correspondencia

Patrocinio y reconocimiento
Imprimir esta página
 
 
 
 
 
 
 
 
 
 
 
 
Está expresamente prohibida la redistribución y la redifusión de todo o parte de los contenidos de la Sociedad Iberoamericana de Información Científica (SIIC) S.A. sin previo y expreso consentimiento de SIIC.
ua31618
Inicio/Home

Copyright siicsalud © 1997-2024 ISSN siicsalud: 1667-9008