1. 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

2. Jorge Burbano Castro
Jose Santiago Camacho Quintero
Tercer semestre de medicina
Profesora: Lina María Martinez
Sánchez

3. INTRODUCTION

4. MITOCHONDRIA
6. More than
6. More than 1. ItIt provides
1. provides
150 diseases
150 diseases Energy to the
Energy to the
related to the
related to the cell, for the
cell, for the
mitochondria
mitochondria different
different
processes . .
processes
5. Main
5. Main
function:
function: 2. Has its
Intracellular
Intracellular
2. Has its Proteins
Proteins
Metabolites
Metabolites organelle own genetic
own genetic for its
organelle for its
oxidation and
oxidation and code
obtaining ATP
code activity
activity
obtaining ATP
4.4. Krebs' cycle
Krebs' cycle 3.Outer
3.Outer
Beta oxidation
Beta oxidation membrane, inner
membrane, inner
membrane,
membrane,
Oxidative
Oxidative intermembrane
intermembrane
phosphorylation
phosphorylation space,
space, cristae,
cristae,
Electron chains matrix
matrix
Electron chains

6. KIDNEY
Ions, water -Renal corpuscle
waste and -Proximal convoluted
excesses to and things In the form
tubule
the tubules which the of urine -Loop of henle
body could (2L/day). -Distal convoluted
tubule
need.

8. ATEROSCLEROSIS

10. RENAL ARTERY
below the
superior
mesenteric
artery

11. STENOSIS

12. INTEGRATION

13. MAIN OBJECTIVE

15. MATERIALES Y
MÉTODOS

16. ANIMALES

17. ANGIOGRAFÍA

18. para Imágenes

19. ELISA

21. WESTERN BLOT

23. RESULTADOS

25. 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

26.  En ARAS+Bendavia aumento la densidad
microvascular de los vasos renales corticales.
 Normaliza el aumento de diámetro del vaso y
tortuosidad.

27. ARAS + Bendavia iguala o
aumenta la expresión renal
de VEGF y sus receptores
ARAS + Bendavia disminuyo
la producción de anión
superóxido en riñón
postestenotico

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

30. ARAS + Bendavia disminuye los
niveles de MCP-1
ARAS + Bendavia disminuyó la
producción de macrófagos CD163

31. Con Bendavia normalizó la expresión
renal de TNF-α

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

33. 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

34. Autors Hypothesis Agreement or disagreement
Niimi K, Yasui T, Hirose M, Hamamoto S, Excessive ROS production leads to mPTP They agree with the authors of this article,
Itoh Y, Okada A, Kubota Y, Kojima Y, opening and release of cytochrome-C into because one of the objectives of the treatment
Tozawa K, Sasaki S, Hayashi Y, Kohri K. the cytosol, which triggers not only was to see if Bendavia can reduce the production
apoptosis (by activating caspase-3 and -9) of ROS and activation of apoptosis after PTRA in
but also tubular damage via release of ARAS.
mitochondrial ROS into the cytosol.
Lerman LO, Textor SC, Grande JP. ARAS activates multiple mechanisms that They agree because when a patient is treated with
increase oxidative damage, apoptosis, bendavia the goal is to reduce the mechanism
inflammation, and interstitial fibrosis, that may contribute to worsening renal
leading to progressive renal dysfunction. dysfunction.
Szeto HH, Liu S, Soong Y, Wu D, Darrah SF, Moreover, it prevents interstitial fibrosis They are agree because one of the results of this
Cheng FY, Zhao Z, Ganger M, Tow CY, and accelerated tubular regeneration in rat article was that those that were treated with
Seshan SV. acute IRI 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 Renal inflammation is a critical determinant They are agree because in animals that were
R, Guglielmotti A, Lerman A, Lerman LO. of disease progression in ARAS. Increased treated with Bendavia reduced number of
oxidative stress is associated with macrophages CD163, preventing oxidative stress.
macrophage and lymphocyte infiltration
into the stenotic swine kidney24

35. CONCLUSIONS

36.  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

37. 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.

38. MAPAS