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Disclosure of Interest
JULIO PASCUAL
Scientific advice to companies:
Novartis
Travel refunds, congress registration fees:
Novartis
Research grant:
Abbvie, Amgen

The details of each Disclosure of Interest are available at the Invited Speakers desk (located in the Registration Area).

LOSS OF ACE2 ACCENTUATED RENAL

HYPERTROPHY AND ANGII-INDUCED
HYPERTENSION IN DIABETIC MICE
Sergi Clotet, Mara Jos Soler, Marta Rebull, Julio Pascual and Marta Riera.
Department of Nephrology, Hospital del Mar-Institut Hospital del Mar dInvestigacions
Mdiques, Barcelona, Spain.

London, May 29, 2015.

INTRODUCTION
Chronic Kidney Disease (CKD) is caracteritzed by an irreversible
deterioration of renal function that gradually progresses to renal failure
(Levey et al. Kidney Int, 2005).

Diabetic Nephropathy (DN) is the leading cause of CKD in our society

(Brenner et al. N Engl J Med, 2001).

Renin Angiotensin System (RAS) Important regulator of cardiac and

renal function (Taal et al. Kidney Int. 2000).
Angiotensin II (AngII) has been shown to promote renal
vasoconstriction, albuminuria, fibrosis, apoptosis and inflammation
(Jennings et al. Am J Physiol Renal Physiol. 2012).

ANGII effects in kidney function

GLOMERULUS

BLOOD VESSEL

ANGII

COOH

NH2
D

COOH
P

ANGII

COOH

NH2

NH2

TUBULOINTERSTITIUM

NH2

COOH
D

ANGII

COOH

NH2
D

NH2

COOH
Y

AT1R

AT1R

AT1R

Vasoconstriction
Hypertension
ROS generation
Endothelial dysfunction
Atherosclerosis
Thrombosis

ROS generation
Mesangial matrix accumulation
GFR Alterations
Glomerulosclerosis
Podocyte loss
Albuminuria

Na reabsorption
ROS generation
Monocyte-macrophage infiltration
Interstitial fibrosis

ANGII infusion in the STZ model

Nicholas et al., Am J Nephrol 2004

ANGII infusion in non-DB ACE2KO mice

Ang II infusion

ACE2KO male mice

WT male mice

Crowley et al., PNAS 2006

AIM

To analize the effect of ACE2

deletion on diabetic and AngIIinfused female mice.

METHODS: Animal model

ACE2KO

WT

SHAM operated
NH2

COOH

GENOTYPING
ANGII-infused
(1.44g/daygr)
4 weeks

8 weeks of DB

18 weeks

4 weeks of ANGII

22 weeks

END-POINT

10 weeks

C57BL/6 females

TYPE 1 DIABETES INDUCTION

STZ: 150mg/Kg IP (2 doses)
Vehicle: Sodium Citrate 0.05M pH4.5

CONT

DB

Parameters assessed:
Blood glucose
Body, Kidney and Heart Weight
Systolic and Diastolic Blood Pressure
Heart Rate
Urinary Albumin Excretion

METHODS: Study groups

n = 10

Female WT-CONT + SHAM

n = 12

Female WT-CONT + ANGII

n = 11

Female WT-DB + SHAM

n = 11

Female WT-DB + ANGII

n = 10

Female ACE2KO-CONT + SHAM

n = 10

Female ACE2KO-CONT + ANGII

n = 10

Female ACE2KO-DB + SHAM

n=9

Female ACE2KO-DB + ANGII

WT-CONT

WT

WT-DB

C57BL/6

ACE2KO
CONT

ACE2KO

ACE2KO
DB

RESULTS: Blood glucose

$
$

$
$

* p<0.05 vs. SHAM; $ p<0.05 vs CONT; # p<0.05 vs WT

RESULTS: Blood glucose

*$#

$
$#
$#

$
$
$

$
$
$

$
$
$
$

$
$

* p<0.05 vs. SHAM; $ p<0.05 vs CONT; # p<0.05 vs WT

RESULTS: Blood glucose (end of follow-up)

$
$

$ p<0.05 vs CONT

RESULTS: Body weight (end of follow-up)

$ p<0.05 vs CONT

RESULTS: Blood pressure (end of follow-up)

Systolic Blood
Pressure (mmHg)

150

*#

140

130

120

SHAM
110

ANGII

100
90
80

WT-CONT

WT-DB

ACE2KO-CONT

Diastolic Blood
Pressure (mmHg)

130

*#

ACE2KO-DB

*#

110

*
SHAM
ANGII

90

70

50

WT-CONT

WT-DB

ACE2KO-CONT

ACE2KO-DB

* p<0.05 vs. SHAM; # p<0.05 vs WT

RESULTS: Kidney weight and Urinary albumin excretion (end of follow-up)

*#

$
*

*#
$

* p<0.05 vs. SHAM; $ p<0.05 vs CONT; # p<0.05 vs WT

RESULTS: Heart weight and heart rate (end of follow-up)

*#

*#

$ $

* p<0.05 vs. SHAM; $ p<0.05 vs CONT; # p<0.05 vs WT

CONCLUSION

Loss of ACE2 accentuated renal

hypertrophy and ANGII-induced
hypertension, albuminuria and cardiac
hypertrophy in type 1 diabetic female
mice.

Blood Vessel

Serum ACE

Blood
Pressure

Vasoconstriction
Serum ACE2

Ang-I
NH2

Ang-(1-7)

Ang-II
P

COOH NH2

COOH
D

NH2

COOH
D

High
BG

NH2

Tissue ACE

COOH

AT1R
Tissue ACE2

0
Cardiac hypertrophy

Renal hypertrophy and albuminuria

Blood Vessel

Serum ACE

Blood
Pressure

Vasoconstriction
Serum ACE2

Ang-II

Ang-I
NH2

COOH NH2

Ang-(1-7)
COOH

NH2

High
BG

ACE2 Defficiency

NH2

COOH
D

Tissue ACE

COOH

AT1R
Tissue ACE2

0
Cardiac hypertrophy

Renal hypertrophy and albuminuria

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