Erectile dysfunction in hypercholesterolemic atherosclerotic apolipoprotein E knockout mice.
BACKGROUND
Erectile dysfunction (ED) and cardiovascular diseases share the same risk factors. Although the use of hypercholesterolemic rabbit models has proven to be useful to illustrate the link between ED and hypercholesterolemia, the cost of daily maintenance of the animals and necessity for important amounts of drug have limited their use.


OBJECTIVE
We aimed to develop a new model of atherosclerosis-associated ED in a well-known experimental model of atherosclerosis, the apolipoprotein E knockout (ApoE KO) mouse.


METHODS
Erectile function was evaluated by recording frequency-dependent increases in intracavernous pressure following electrical stimulation of the cavernous nerve in 26-, 32-, and 38-week-old ApoE KO mice fed a Western-type diet and age-matched C57BL6/J anesthetized mice. Atherosclerotic lesions were evaluated by planimetry in oil red O-stained aortas.


RESULTS
We found that in contrast to C57BL6/J mice, ApoE mice displayed atherosclerotic lesions covering 22% of the aortic luminal surface at 26 weeks of age and increasing to 27% and 35% at 32 weeks and 38 weeks of age, respectively. The amplitude of erectile responses to electrical stimulation of the cavernous nerve was markedly impaired in 26-week-old ApoE KO mice as compared with age-matched C57BL6/J mice. Impairment in erectile function persisted in ApoE KO mice 32 and 38 weeks of age.


CONCLUSIONS
The ApoE KO mouse, a well-characterized model to study disorders associated with hypercholesterolemia and atherosclerosis in cardiovascular research, could therefore be suitable for investigation of disease-modifying effects of new therapeutic strategies aiming to target both atherosclerosis and ED.
Behr-Roussel
Delphine
D
Pelvipharm, Gif sur Yvette, France.
Darblade
Benoit
B
Pelvipharm, Gif sur Yvette, France.
Oudot
Alexandra
A
Pelvipharm, Gif sur Yvette, France.
Compagnie
Sandrine
S
Pelvipharm, Gif sur Yvette, France.
Bernabé
Jacques
J
Pelvipharm, Gif sur Yvette, France.
Alexandre
Laurent
L
Pelvipharm, Gif sur Yvette, France.
Giuliano
François
F
Neuro-Urology Unit, Andrology Unit, Department of Physical Medicine and Rehabilitation, Raymond Poincaré Hospital, Garches, France. Electronic address: giuliano@cyber-sante.org.
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000378:metabolism; D050197:Atherosclerosis / Q000150:complications / Q000503:physiopathology*; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism; D007172:Erectile Dysfunction / Q000209:etiology / Q000503:physiopathology*; D006937:Hypercholesterolemia / Q000150:complications / Q000503:physiopathology*; D018783:Impotence, Vasculogenic / Q000209:etiology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D001057:Apolipoproteins E