title: The JCR:LA-cp rat: a novel rodent model of cystic medial necrosis.
abstract: Although there are multiple rodent models of the metabolic syndrome, very few develop vascular complications. In contrast, the JCR:LA-cp rat develops both metabolic syndrome and early atherosclerosis in predisposed areas. However, the pathology of the normal vessel wall has not been described. We examined JCR:LA control (+/+) orcp/cprats fed normal chow diet for 6 or 18 mo. JCR:LA-cp rats developed multiple features of advanced cystic medial necrosis including "cysts," increased collagen formation and proteoglycan deposition around cysts, apoptosis of vascular smooth muscle cells, and spotty medial calcification. These appearances began within 6 mo and were extensive by 18 mo. JCR:LA-cp rats had reduced medial cellularity, increased medial thickness, and vessel hypoxia that was most marked in the adventitia. In conclusion, the normal chow-fed JCR:LA-cp rat represents a novel rodent model of cystic medial necrosis, associated with multiple metabolic abnormalities, vascular smooth muscle cell apoptosis, and vessel hypoxia.NEW & NOTEWORTHYTriggers for cystic medial necrosis (CMN) have been difficult to study due to lack of animal models to recapitulate the pathologies seen in humans. Our study is the first description of CMN in the rat. Thus the JCR:LA-cp rat represents a useful model to investigate the underlying molecular changes leading to the development of CMN.
authors.affiliation: Department of Biomedical Science, University of Nottingham (Malaysia Campus), Semenyih, Selangor, Malaysia; yuhfen.pung@nottingham.edu.my.
authors.forename: Yuh Fen
authors.identifier: http://orcid.org/0000-0001-6195-3970
authors.initials: YF
authors.lastname: Pung
authors.affiliation: Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio.
authors.forename: William M
authors.initials: WM
authors.lastname: Chilian
authors.affiliation: Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom; and.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Bennett
authors.affiliation: Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom; and.
authors.forename: Nichola
authors.initials: N
authors.lastname: Figg
authors.affiliation: Department of Cardiothoracic Surgery, Serdang Hospital, Kajang, Selangor, Malaysia.
authors.forename: Mohd Hamzah
authors.initials: MH
authors.lastname: Kamarulzaman
mesh_terms: D000818:Animals; D017545:Aortic Aneurysm, Thoracic / Q000235:genetics* / Q000473:pathology; D050197:Atherosclerosis / Q000473:pathology; D001786:Blood Glucose / Q000378:metabolism; D001808:Blood Vessels / Q000473:pathology; D001835:Body Weight; D003094:Collagen / Q000096:biosynthesis; D003560:Cysts / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D000860:Hypoxia; D008055:Lipids / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics* / Q000473:pathology; D009336:Necrosis; D011509:Proteoglycans / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D001786:Blood Glucose; D008055:Lipids; D011509:Proteoglycans; D003094:Collagen
keywords: hypoxia; leptin; metabolic syndrome; rodent model