title: Osborne-Mendel rats simultaneously develop cardiac and renal dysfunction, left atrial thrombosis, peripheral artery occlusion, and ascending aortic dissection.
abstract: Although chronic kidney disease (CKD) is strongly associated with onsets of cardiovascular disease (CVD), the pathogenic mechanism between these diseases has not been fully understood. To develop and validate new therapeutic strategies for this complication, appropriate experimental models that reflect the complexity of the underlying pathophysiology are needed. The Osborne-Mendel (OM) rat was identified as an atherosclerosis-prone and a premature-death rat strain among 16 inbred rat strains when fed high-cholesterol containing diet. When fed high-cholesterol diet, OM rats showed simultaneous occurrence of aortic aneurysm, aortic dissection, peripheral artery occlusion, and left atrial thrombosis. OM rats had significantly lower max dP/dt and higher min dP/dt than F344 rats did, indicating impaired left ventricle contractility and relaxation. OM rats developed renal dysfunction, showing increased urinary albumin excretion. OM rats also showed mild hypertension, decreased endothelial function, and enhanced coagulation and platelet aggregation, compared with F344 rats. We now report that OM rat would be a novel spontaneous animal model which simultaneously demonstrates cardiac and renal dysfunction, and CVD events. This model could be a useful model for the pre-clinical testing of pharmacological therapies and could provide new insight into potential targets and pathways for the treatment of CKD and CVD.
authors.affiliation: Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd., 26-1, Muraoka-Higashi 2chome, Fujisawa, Kanagawa, 251-8555, Japan. Electronic address: makoto.asahina@takeda.com.
authors.forename: Makoto
authors.initials: M
authors.lastname: Asahina
authors.affiliation: Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd., 26-1, Muraoka-Higashi 2chome, Fujisawa, Kanagawa, 251-8555, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Matsumoto
authors.affiliation: Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd., 26-1, Muraoka-Higashi 2chome, Fujisawa, Kanagawa, 251-8555, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Yasuhara
authors.affiliation: Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd., 26-1, Muraoka-Higashi 2chome, Fujisawa, Kanagawa, 251-8555, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Suzuki
authors.affiliation: Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd., 26-1, Muraoka-Higashi 2chome, Fujisawa, Kanagawa, 251-8555, Japan.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Takami
authors.affiliation: Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd., 26-1, Muraoka-Higashi 2chome, Fujisawa, Kanagawa, 251-8555, Japan.
authors.forename: Michiyasu
authors.initials: M
authors.lastname: Takeyama
authors.affiliation: Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd., 26-1, Muraoka-Higashi 2chome, Fujisawa, Kanagawa, 251-8555, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Tozawa
mesh_terms: D000818:Animals; D001014:Aortic Aneurysm / Q000209:etiology / Q000503:physiopathology*; D001157:Arterial Occlusive Diseases / Q000209:etiology / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000633:toxicity; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D006325:Heart Atria; D006331:Heart Diseases / Q000209:etiology / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D058729:Peripheral Arterial Disease / Q000209:etiology / Q000503:physiopathology*; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D013045:Species Specificity; D016019:Survival Analysis; D013927:Thrombosis / Q000209:etiology / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D002791:Cholesterol, Dietary
keywords: Animal model; Cardiovascular diseases; Osborne-Mendel rat