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

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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


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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



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Bibliografía del artículo
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