SHAPE Society

1. Parallel exercise training reverses
vascular dysfunction in
hypercholesterolemic rabbits
Yang AL1
, Jen CJ1,2
, and Chen HI1,2
*
Institute of Basic Medical Sciences1
,
Department of Physiology2
, National Cheng
Kung University, Tainan 701, TAIWAN

2. Motivation
Endothelial dysfunction is an early event in
atherosclerosis.
Expression of pro-inflammatory molecules is
upregulated in atherosclerosis.
Chronic exercise enhances endothelium-dependent
vasodilating responses in normal or hypertensive
animals.
We hypothesize that chronic exercise improves
vascular endothelial function and reduces the
expression of pro-inflammatory molecules in
hypercholesterolemic rabbits at early stages.

3. Methods I
• Animal models:
Male New Zealand White rabbits were divided into 4
groups: normal diet control(N); 2% high cholesterol
diet control(H); normal diet with exercise(NE); and
high cholesterol diet with exercise(HE).
• Exercise protocol:
Rabbits in exercise groups received running exercise
training on a leveled treadmill for 2, 4, 6, or 8 weeks
in total.

4. Methods II
• Oil red O staining:
to determine lipid deposition as fatty streaks
• Dose responses of ACh–induced
vasorelaxation in aortas
• Immunostaining of pro-inflammatory
molecules, i.e., adhesion molecules (P-
selectin, VCAM-1), MCP-1, and iNOS

5. Oil red O-stained thoracic aortas
(8 wk intervention)
N H
NE HE

6. ----------------------------------------------------------------------------------
Lipid Deposit (% surface area)
Group ------------------------------------------------------------------------
2wk 4wk 6wk 8wk
----------------------------------------------------------------------------------
H 1.5+0.3(6) 26+10(5) 32+8(9) 48+10(9)
HE 1.5+1.0(6) 8+3 (6)* 11+5(9)* 40+8(9)
----------------------------------------------------------------------------------
Data are expressed as mean +SEM.
Numbers in the parentheses indicate the numbers of
animals used in each group.
* P<0.05 (HE vs. H)
Exercise reduces high-cholesterol diet-evoked
lipid deposition in rabbit aortas

7. High cholesterol diet feeding impairs vasorelaxation,
whereas concomitant exercise reduces the impairment

8. Immunostaining of pro-inflammatory molecules
(6 wk intervention)
100µm

9. ----------------------------------------------------------------------------------
Group P-selectin VCAM-1 MCP-1 iNOS
----------------------------------------------------------------------------------
4wk
H 1.67+0.40 1.85+0.45 1.27+0.45 1.22+0.37
HE 0.38+0.15* 0.23+0.15* 0.36+0.18* 0.28+0.14*
6wk
H 2.22+0.35 1.63+0.21 1.76+0.28 2.42+0.23
HE 0.87+0.35* 0.43+0.14* 0.55+0.18* 0.93+0.36*
8wk
H 1.95+0.44 1.68+0.23 2.27+0.30 2.33+0.27
HE 0.73+0.19* 1.07+0.14* 1.28+0.21* 1.25+0.10**
----------------------------------------------------------------------------------
Data are expressed as mean +SEM.
* P<0.05; **P<0.01 (HE vs. H)
Exercise reduces high-cholesterol diet-induced
protein expression in rabbit aortas

10. Conclusion
High cholesterol diet feeding induces
lipid deposition and the expression of
pro-inflammatory molecules, and
impairs vascular responsiveness.
Parallel exercise training ameliorates
vascular structural changes and
improves endothelial function in
hypercholesterolemia.

11. Bibliography
Yang AL, Chen HI. Chronic exercise reduces
adhesion molecules/iNOS expression and
partially reverses vascular responsiveness in
hypercholesterolemic rabbit aortae.
Atherosclerosis 2003
Yang AL, Jen CJ, Chen HI. Effects of high
cholesterol diet and parallel exercise training
on the vascular function of rabbit aortas: a
time course study. J Appl Physiol 2003