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Drug evaluation using pharmacologically induced aortic dissection prone model mice
Yuki Izawa-Ishizawa(%, Mitsuhiro Goda)%, Fuka Aizawa*%, Yoshito Zamami*!+%, Hirofumi Hamano+%,Kenta Yagi)%, Yasumasa Ikeda(%, Keisuke Ishizawa*!+%, and Toshiaki Tamaki,%(%Department of Pharmacology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan)%Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital, Tokushima, Japan*%

Department of Pharmacy, Tokushima University Hospital, Tokushima, Japan+%

Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences,Tokushima, Japan,%

Anan Medical Center, Tokushima, JapanSUMMARY
Aortic dissection$or dissecting aortic aneurysm%is a condition in which the aortic wall isseparated into two layers at the medial level to form a pseudocavity.
#entry, allows blood to tear through the medial layer and flow in.

The intima crack, called theThe location of the #entry andthe extent of the dissection can cause a variety of serious complications, including rupture, cardiac
tamponade, and obstruction of branched vessels.

According to the Guideline on Diagnosis andTreatment of Aortic Aneurysm and Aortic Dissection )')', it is estimated that -("+& of the onsetof dissection die before arrival at the hospital, and .*& will die within )+ hours after the onset.

It

has been suggested that the morbidity rate has been increasing in recent years.

Since many ofthem have a fatal prognosis, it is an important issue to prevent the onset itself.

However, noeffective therapeutic agent or preventive strategy has been established so far.

The first reason isthat it is extremely difficult to design clinical studies because aortic dissection traced the rapid onset
and progression.

The second is that the pathophysiology and preventive drug search are notsufficiently conducted even at the basic research level.

Epidemiologically, the results of theInternational Registry of Aortic Dissection$IRAD%revealed that aging, hypertension, atherosclerosis, and hereditary connective tissue diseases are risk factors.
similar pathological conditions caused by these risk factors.

The aortic aneurysm also shows

However, one of the major differences

between aneurysm and dissection is the presence of aortic intima rupture.

Therefore, we attemp-

ted to establish a mouse model developing dissection at a high rate by adding the endothelial
dysfunction to a pharmacologically induced aortic aneurysm model mouse.

Furthermore, weevaluated the efficacy of pitavastatin and several nutrients using our novel model mice and verified
its usefulness as a model animal.

Key words : aortic dissection, endothelial dysfunction, statin, polyphenol, large medical databases