A Mitochondrial Permeability Transition Pore Inhibitor Improves Renal Outcomes After

Revascularization in Experimental Atherosclerotic Renal Artery Stenosis

Alfonso Eirin, Zilun Li, Xin Zhang, James D. Krier, John R. Woollard, Xiang-Yang Zhu, Hui Tang, Sandra M. Herrmann, Amir Lerman, Stephen C. Textor, Lilach O. Lerman

AHA Journals

Jorge Burbano Castro Jose Santiago Camacho Quintero

Tercer semestre de medicinaProfesora: Lina María Martinez

Sánchez

INTRODUCTION

1. It provides Energy to the cell, for the

different processes .

1. It provides Energy to the cell, for the

different processes .

6. More than 150 diseases related to the mitochondria

6. More than 150 diseases related to the mitochondria

Intracellular organelle

Intracellular organelle

2. Has its own genetic

code

2. Has its own genetic

code

3.Outer membrane, inner membrane, intermembrane space, cristae, matrix

3.Outer membrane, inner membrane, intermembrane space, cristae, matrix

4. Krebs' cycleBeta oxidation

Oxidative phosphorylationElectron chains

4. Krebs' cycleBeta oxidation

Oxidative phosphorylationElectron chains

Proteins for its

activity

Proteins for its

activity

5. Main function:

Metabolites oxidation and obtaining ATP

5. Main function:

Metabolites oxidation and obtaining ATP

MITOCHONDRIA

KIDNEY

waste and excesses to the tubules

Ions, water and things which the

body could need.

In the form of urine (2L/day).

-Renal corpuscle-Proximal convoluted tubule-Loop of henle-Distal convoluted tubule

ATEROSCLEROSIS

RENAL ARTERY

below the superior mesenteric artery

STENOSIS

INTEGRATION

MAIN OBJECTIVE

MATERIALES Y MÉTODOS

ANIMALES

ANGIOGRAFÍA

para Imágenes

ELISA

WESTERN BLOT

RESULTADOS

Valores de terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) y caspasa-3 estuvieron elevados en ARAS pero en menor proporción en los tratados con Bendavia.

Bendavia redujo expresión de Bax (proapoptótico)

expresión de PGC-1, FNR-1, GABP, PPAR-α

expresión de HO-1, PPAR-δ

Se restaura SIRT-1

En ARAS+Bendavia aumento la densidad microvascular de los vasos renales corticales.

Normaliza el aumento de diámetro del vaso y tortuosidad.

ARAS + Bendavia iguala o aumenta la expresión renal de VEGF y sus receptores

ARAS + Bendavia disminuyo la producción de anión superóxido en riñón postestenotico

ARAS + Bendavia disminuyó la expresión de p47 y nitrotirosina (NT)

ARAS + Bendavia disminuye los niveles de MCP-1

ARAS + Bendavia disminuyó la producción de macrófagos CD163

Con Bendavia normalizó la expresión renal de TNF-α

Pacientes con ARAS, lesión tubular, fibrosis intersticial y glomerular estuvieron elevados, ARAS + Bendavia disminuidos.

Disminución del daño tubular

La inmunotinción de fibronectina y colágeno IV se redujo en Bendavia

Expresión de plaminógeno inhibidor- 1 se atenuó tanto en tratamiento con PTRA con o sin Bendavia , pero solo la expresión de TGF-β1 se restauró con Bendavia

Autors Hypothesis Agreement or disagreement

Niimi K, Yasui T, Hirose M, Hamamoto S, Itoh Y, Okada A, Kubota Y, Kojima Y, Tozawa K, Sasaki S, Hayashi Y, Kohri K.

Excessive ROS production leads to mPTP opening and release of cytochrome-C into the cytosol, which triggers not only apoptosis (by activating caspase-3 and -9) but also tubular damage via release of mitochondrial ROS into the cytosol.

They agree with the authors of this article, because one of the objectives of the treatment was to see if Bendavia can reduce the production of ROS and activation of apoptosis after PTRA in ARAS.

Lerman LO, Textor SC, Grande JP. ARAS activates multiple mechanisms that increase oxidative damage, apoptosis, inflammation, and interstitial fibrosis, leading to progressive renal dysfunction.

They agree because when a patient is treated with bendavia the goal is to reduce the mechanism that may contribute to worsening renal dysfunction.

Szeto HH, Liu S, Soong Y, Wu D, Darrah SF, Cheng FY, Zhao Z, Ganger M, Tow CY, Seshan SV.

Moreover, it prevents interstitial fibrosis and accelerated tubular regeneration in rat acute IRI

They are agree because one of the results of this article was that those that were treated with Bendavia normalized the expression of TGF-β and plasminogen-activator inhibitor-1 that are synthesized by inflammatory cells and can help to the development of intersticial fibrosis.

Zhu XY, Chade AR, Krier JD, Daghini E, Lavi R, Guglielmotti A, Lerman A, Lerman LO.

Renal inflammation is a critical determinant of disease progression in ARAS. Increased oxidative stress is associated with macrophage and lymphocyte infiltration into the stenotic swine kidney24

They are agree because in animals that were treated with Bendavia reduced number of macrophages CD163, preventing oxidative stress.

CONCLUSIONS

This work helped us to improve our comunicative habilities in other language different than spanish

These activities help to promote the investigation, keep us informed with the changes in today’s medicine and prepare us to face the future. It’s the must of people in a medical formation to keep actualized of the news about this changing world

Learning about things which are important, for example: to explore etiologically the human being for helping him and by this way, get the goal of the real medical mission.

It’s good to do this type of activities because stimulate the laboral and interpersonal relations with the classmates, essential dimension of the medical professional.

MAPAS