title: The degeneration of biological cardiovascular prostheses under pro-calcific metabolic conditions in a small animal model.
abstract: In order to allow for a comparative evaluation of the in vivo degeneration of biological and tissue-engineered heart valves and vascular grafts, a small animal model of accelerated cardiovascular calcification is desired. Wistar rats (n = 102; 6 groups) were fed ad libitum with regular chow and 5 different regimens of pro-calcific diet supplemented with combinations of vitamin D (VD), cholesterol (CH) and dicalcium phosphate (PH). Moreover, cryopreserved (n = 7) or detergent-decellularized rat aortic conduit grafts (n = 6) were infrarenally implanted in Wistar rats under severely pro-calcific conditions. The follow-up lasted up to 12 weeks. High-dose application of VD (300,000 IU/kg), CH (2%) and PH (1.5%) resulted in elevated serum calcium and cholesterol levels as well as LDL/HDL ratio. It increased the tissue MMP activity visualized by in situ zymography and caused significantly aggravated calcification of the native aortic valve as well as the aortic wall as assessed by histology and micro-computed tomography. (Immuno)histology and quantitative real-time PCR revealed chondro-osteogenic cell transformation, lipid deposition, nitrosative stress and low-level inflammation to be involved in the formation of calcific lesions. Despite pro-calcific in vivo conditions, decellularization significantly reduced calcification, inflammation and intimal hyperplasia in aortic conduit implants. A well balanced dietary trigger for pathologic metabolic conditions may represent an appropriate mid-term treatment to induce calcifying degeneration of aortic valves as well as vascular structures in the systemic circulation in rats. With respect to experimental investigation focusing on calcifying degeneration of native or prosthetic tissue, this regimen may serve as a valuable tool with a rapid onset and multi-facetted character of cardiovascular degeneration.
authors.affiliation: Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Moorenstrasse 5, Duesseldorf 40225, Germany. Electronic address: alexander.assmann@med.uni-duesseldorf.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Assmann
authors.affiliation: Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Moorenstrasse 5, Duesseldorf 40225, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Zwirnmann
authors.affiliation: Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Moorenstrasse 5, Duesseldorf 40225, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Heidelberg
authors.affiliation: Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Moorenstrasse 5, Duesseldorf 40225, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Schiffer
authors.affiliation: Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Moorenstrasse 5, Duesseldorf 40225, Germany.
authors.forename: Kim
authors.initials: K
authors.lastname: Horstkötter
authors.affiliation: Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Moorenstrasse 5, Duesseldorf 40225, Germany.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Munakata
authors.affiliation: Department of Experimental Molecular Imaging, RWTH-Aachen University, Medical Faculty, Pauwelsstr. 30, Aachen D-52074, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Gremse
authors.affiliation: Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Moorenstrasse 5, Duesseldorf 40225, Germany.
authors.forename: Mareike
authors.initials: M
authors.lastname: Barth
authors.affiliation: Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Moorenstrasse 5, Duesseldorf 40225, Germany. Electronic address: artur.lichtenberg@med.uni-duesseldorf.de.
authors.forename: Artur
authors.initials: A
authors.lastname: Lichtenberg
authors.affiliation: Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Moorenstrasse 5, Duesseldorf 40225, Germany.
authors.forename: Payam
authors.initials: P
authors.lastname: Akhyari
mesh_terms: D000818:Animals; D001021:Aortic Valve / Q000378:metabolism* / Q000473:pathology; D001705:Bioprosthesis; D002114:Calcinosis / Q000378:metabolism* / Q000473:pathology; D004032:Diet; D004195:Disease Models, Animal; D006349:Heart Valve Diseases / Q000378:metabolism* / Q000473:pathology; D006350:Heart Valve Prosthesis; D019918:Heart Valve Prosthesis Implantation; D008297:Male; D017208:Rats, Wistar
keywords: Animal model; Aortic valve sclerosis; Atherosclerosis; Decellularization; Heart valve prosthesis; Vitamin D