University of Oulu

Juha Näpänkangas, Pasi Ohtonen, Pauli Ohukainen, Jonna Weisell, Timo Väisänen, Tuomas Peltonen, Panu Taskinen, Jaana Rysä, Increased mesenchymal podoplanin expression is associated with calcification in aortic valves, Cardiovascular Pathology, Volume 39, 2019, Pages 30-37, ISSN 1054-8807,

Increased mesenchymal podoplanin expression is associated with calcification in aortic valves

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Author: Näpänkangas, Juha1; Ohtonen, Pasi2; Ohukainen, Pauli3;
Organizations: 1Department of Pathology, Cancer Research and Translational Medicine Research Unit, University of Oulu and Oulu University Hospital, Finland
2Division of Operative Care and MRC Oulu, Oulu University Hospital and University of Oulu, Finland
3Research Unit of Biomedicine, Computational Medicine, University of Oulu, Finland
4School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
5Research Unit of Biomedicine, Pharmacology and Toxicology, University of Oulu, Finland
6Department of Cardiovascular Surgery, Oulu University Hospital and University of Oulu, Finland
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 10.9 MB)
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Language: English
Published: Elsevier, 2019
Publish Date: 2019-12-07


Background and aim of the study: Calcific aortic valve disease (CAVD) is a progressive disease starting from mild valvular sclerosis and progressing to severe aortic stenosis (AS) with calcified valves. The origin of the calcification is proposed to be mesenchymal cells which have differentiated towards an osteoblastic phenotype. Podoplanin is a glycoprotein expressed in the endothelium of lymphatic vessels and in osteoblasts and osteocytes, mesenchymal cells, as well as in many carcinomas and aortic atherosclerotic lesions. In CAVD, its expression has been evaluated only as a marker of the lymphatic vasculature.

Materials and methods: We determined podoplanin expression in human aortic valves in four patient groups: control (C, n=7), aortic regurgitation (AR, n=8), aortic regurgitation and fibrosis (AR + f, n=15) and AS (n=49) by immunohistochemistry and quantitative real-time PCR (RT-PCR).

Results: Immunohistochemically, podoplanin expression was significantly increased in AR + f and AS groups when compared with the control and AR groups and the level of expression positively correlated with the extent of calcification and vascularity. Podoplanin mRNA levels were 1.7-fold higher in the AS group as compared with the control group (P=.05). Podoplanin-positivity was present not only in lymphatic vessel endothelium but also in osteoblasts, osteocytes, chondrocytes, macrophages and extracellular matrix. The majority of the podoplanin-positivity was in spindle cells with a myofibroblastic phenotype, often associated with calcifications. Tricuspid valves had more calcification-associated podoplanin than bi/unicuspid valves (median 1.52 vs 1.16, P<.001).

Conclusions: CAVD is characterized by an increased expression of podoplanin; this is associated with the differentiation of valvular interstitial cells into calcium-producing, myofibroblast-like cells. In addition, tricuspid valves express relatively more podoplanin than bi/unicuspid valves.

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Series: Cardiovascular pathology
ISSN: 1054-8807
ISSN-E: 1879-1336
ISSN-L: 1054-8807
Volume: 39
Pages: 30 - 37
DOI: 10.1016/j.carpath.2018.11.006
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3121 General medicine, internal medicine and other clinical medicine
Funding: The study was funded by the Academy of Finland (grants 276747, 284504 and 312611), the Finnish Foundation for Cardiovascular Research and the Orion Research Foundation.
Copyright information: © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license