PDGF-C and -D and their receptors PDGFR-α and PDGFR-β in atherosclerotic human arteries

• Published in: European journal of clinical investigation Vol. 39; no. 4; pp. 320 - 327
• Main Authors: Karvinen, H., Rutanen, J., Leppänen, O., Lach, R., Levonen, A.-L., Eriksson, U., Ylä-Herttuala, S.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2009
• Subjects: Adult; Aged; Aged, 80 and over; Arteries - metabolism; Arteries - pathology; Atherosclerosis - immunology; Atherosclerosis - metabolism; Atherosclerosis - pathology; Atherosclerotic lesion; Female; gene expression; Humans; Immunohistochemistry - methods; immunohistology; Male; Medicin och hälsovetenskap; Middle Aged; platelet derived growth factor; Platelet-Derived Growth Factor - immunology; Platelet-Derived Growth Factor - metabolism; Receptor, Platelet-Derived Growth Factor alpha - immunology; Receptor, Platelet-Derived Growth Factor alpha - metabolism; Receptor, Platelet-Derived Growth Factor beta - immunology; Receptor, Platelet-Derived Growth Factor beta - metabolism; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - metabolism
• ISSN: 0014-2972; 1365-2362; 1365-2362
• DOI: 10.1111/j.1365-2362.2009.02095.x

Background  Platelet derived growth factors (PDGFs) are mitogens for fibroblasts and smooth muscle cells. This growth factor family contains four members PDGF‐A, PDGF‐B, PDGF‐C and PDGF‐D. Biology of recently discovered PDGF‐C and PDGF‐D is not well‐established. Here we studied the expression of PDGF‐C and PDGF‐D and their receptors PDGFR‐α and PDGFR‐β in normal and atherosclerotic human arteries. Materials and methods  Human arterial samples from amputations and autopsies were classified according to the atherosclerotic stage and the expression of PDGF‐C and PDGF‐D proteins and their receptors was studied by immunohistochemistry. In situ hybridization and reverse transcriptase‐PCR were used to study mRNA expression. Results  Both growth factors were expressed in medial smooth muscle cells (SMCs) in normal arteries and atherosclerotic lesions. However, clear differences were found in the expression profiles in endothelium: PDGF‐C was strongly expressed in endothelial cells in both normal arteries and lesions whereas PDGF‐D was only weakly expressed in endothelium. PDGF‐C expression was very prominent in lesion macrophages. PDGF‐D was expressed throughout the artery wall in lesions. PDGFR‐α expression was strong in endothelium and in lesion macrophage‐rich areas, whereas PDGFR‐β was mostly expressed in SMCs. Conclusions  Our results suggest that PDGF‐C may play an important role in endothelium in normal and atherosclerotic arteries and in macrophages in lesions. PDGF‐D was expressed in all types of lesions with the same intensity and thus differs from the expression of PDGF‐C.