Systemic Sclerosis: Gene Expression Profiling by Microarray Technology of Endothelial Cells

Abstract number: P1721

Giusti¹ B, Del Rosso² M, Fibbi² G, Matucci-Cerinic² M, Rossi¹ L, Poggi¹ F, Evangelisti¹ L, Sestini¹ I, Pepe¹ G, Abbate¹ R

¹¹Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence; Azienda Ospedaliero-Universitaria Careggi, Florence, Italy ¹¹Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence; Azienda Ospedaliero-Universitaria Careggi, Florence, Italy ²²Department of Experimental Pathology and Oncology, University of Florence, Italy

Systemic sclerosis (SSc) is a clinically heterogeneous, systemic disorder which affects the connective tissue of the skin, internal organs and the walls of blood vessels. Defective angiogenesis, resulting in tissue ischemia, is prominent in the diffuse form of SSc, but its pathogenetic basis is unknown. We isolated microvascular endothelial cells (MVEC) from the dermis of healthy individuals (N-MVEC) and patients with diffuse SSc (SSc-MVEC) in order to identify differences in the gene expression profiling. For this purpose we used a 14 000 gene oligonucleotide array (70-mers oligonucleotide, Operon technologies). Total RNA from cultured MVEC was isolated by RNeasy Kit (QIAGEN). Pooling of MVEC total RNA from patients and controls was performed. One hundred and ninety nine genes showed altered expression levels between SSc-MVEC and N-MVEC: 153 were up-regulated and 46 were down-regulated. More than 25 of the genes (e.g. MIF, LAMR1, IL-8, CTGF, CFL1, PEA15, PGAR, KLKs, PLAT, PLAU, etc) which were differentially expressed in SSc-MVEC are directly or indirectly involved with angiogenesis. Interestingly, in contrast with the clinical data indicating a vascular desert-like pattern, many proangiogenetic genes were found to be over-expressed in SSc. These results suggest that an epigenetic event which occurs in SSc may be able to vanish the angiogenic attitude of MVEC. Preliminary data indicate that the truncation of the urokinase-plasminogen activator receptor (uPAR) in SSc-MVEC may account, at least in part, for defective angiogenesis.