le système cardiovasculaire: macro et microcirculation · n d h csa (cm2) aorta 1 25 mm 2mm 2.8...
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Le système cardiovasculaire: macro et microcirculation
Bernard LEVYINSERM Hôpital Lariboisière Paris
n D h CSA (cm2)
Aorta 1 25 mm 2mm 2.8
Arteries 40-110000 20 - 0.5 mm 1 - 0.1mm 40
Arterioles 3x10 6 500-20 µm 100 - 10 µm 55
Capillaries 3x 10 9 15 - 5 µm 0.5 µm 1350
3cm2 40 55 1350 cm2
Damping
Reflection
ResistanceExchanges
Few elastic arteriesThousands of muscular arteries Millions of arterioles resistance & reflectionBillions of capillaries diffusion and exchanges
distribution and damping
Shear
Pressure
Mechanical forces in the vascular wall
Internal elastic
lamina
SMC, collagen
PG
Endothelium
External elastic
lamina
Shear Stress = 4 µ Q / π r3 = 4 µ (πr2 V) / π r3 = 4 µ V / r
Tensile stress = P r / h
Smooth muscle
Pressure
Endothelium
Shear stress
abg
K+
AktNO MAPK
ab
g
FAK
MAPK
PKC
Vasodilation
Remodeling or Myogenic tone
P. rh
Tensile stress
Laplace law
Hypertension
Pressure-induced vascular remodelling
ECM synthesis/degradation
VSMC hypertrophy/hyperplasia
0 80 150
Pressure (mmHg)
***
0
1
2
3
4
5
6
7
35S
-Met
(dpm
/mg tis
sue x
10
-3)
0
1
2
3
4
5
6
7
3H
-Td
R
(dpm
/mg tis
sue x
10
-3)
DNA synthesis Protein synthesis
Pressure-induced changes in DNA and protein synthesis
Bardy et al, Circ Res 1995
0 80 150
Pressure (mmHg)
Wong & Langille. Circ Res 1996
Photomicrographs of the internal elastic lamina (IEL) from right common carotid arteries
Role of MMPs in vessel remodelling
MMPs
10 80 150 mmHg
MMP2
MMP9
Lehoux et al. Circulation. 2004.
400
500
600
700
800
900
1000
0 50 100 150 200
Pressure (mmHg)
10 mmHg
80 mmHg
Role of MMPs in vascular remodelling
***
150 mmHg
80 mmHg 150 mmHg
Bardy et al. Circ Res, 1996
70 mmHg 150 mmHg10 mmHg
Strain-induced fibronectin expression in whole aorta
Langille et al. Am J Physiol.1990
Thoracic
aorta
Fetal Post-partum
Arterial pressure (mmHg)
Mechanical factors & physiological remodeling
40
60
Remodelage par contrainte pariétale (Pression)
Pression
Contrainte = Pr/h
Activation Muscle Lisse
Synthèse Protéines
Matrice extracellulaire
Facteurs de croissance
Hypertrophie, hyperplasie
Epaisseur media
Poiseuille’s law
= 4 µ . Q
π . r3
Shear stress
Langille et al. Am J Physiol.1990
Fetal Post-partum
Abdominal
aorta
Abdominal aortic flow
Time (days)
Shear stress and physiological vascular remodelling
Control CCA Flow-loaded CCA
Arteriovenous fistula
Model of arteriovenous fistula
Right common
carotid arteryRight external
jugular vein Left common
carotid artery
Castier et al. Circ Res 2005
0,7
0 7 14 21
Diameter (µm)0.7
0.6
0.5
0.40 7 14 21
Day
RCC
LCC
0 7 14 21
Shear (dynes/cm2)
LCC
RCC
300
200
100
00 7 14 21
High shear stress induces ROS production in arteries of wild-type but not p47 -/- mice
WT
p47-/-
Control AVFCastier et al. Circ Res 2005
eNOS-/-
NOXp22
p67
p47
O2 O2-
NO ONOO-
rac
eNOS
Pro-MMPs
MMPs
Diameter (µm) Shear (dynes/cm2)
0 7 14 21
Day
0.7
0.6
0.5
0.4
0 7 14 21
Day
wt
wtp47-/-
p47-/-
300
200
100
0
Role of ROS in vascular adaptation to blood flow
Castier et al. Circ Res 2005
eNOS-/-
eNOS-/-
Growth factorsproMMPs
SMC growth
DistensionContact Loss
uPA?
plasmin
NOXp22
p67
p47
O2 O2-
NO ONOO-
rac
SHEAR STRESS
MMPs
Matrix degradation
Apoptosis EnlargementHyperplasia
COEUR AORTE ART. DE
RESISTANCE
CAPILLAIRES
VEINES
Système à Haute Pression
Ao
LA
LV
AoLA
LV
Diastole
Systole
TPR
TPR
Damping of pressure and flow
Large arteries in hypertension:RemodelingHypertrophyFibrosisStiffening
•Arteries with significant MT and then Resistance (Diameter < 300 µm) : Intraluminal pressure < Aortic pressure
Resistance arteries:
•The most important in quantity
P. Bruneval
Organization of Smooth Muscle Cells: vasomotor tone
3rd and 4th arteriole generation
CONTROL INTRALUMINAL EXTRALUMINAL
ANGIOTENSINE II
100
µm
Henrion D et al. J Clin Invest. 1997; 100: 2909-2914.
Percentage of passive diameter at 100 mmHg
50
100
10 30 70 110 150 190 230 270 mmHg
Levy et al Circulation 2001; 104:736-741
Endothélium et filtration endothéliale
In vivo Shear Oriented Endothelial Cells
thin (<1µm) and fragile capillary wall
P. Bruneval
