Charité - Universitätsmedizin Berlin
Over the past years, our main focus was to analyze differential gene expression patterns of human neointima to elucidate the molecular mechanisms of neointima formation and atherosclerosis. We applied cDNA array technology to characterize gene expression profiles in specimens of e.g. human neointima retrieved from patients with symptomatic in-stent restenosis by helix cutter atherectomy. Some of the differentially expressed genes complied with expected gene expression patterns of neointima. Additionally, we discovered previously unknown gene expression patterns, such as the upregulation of FK506-binding protein 12 (FKBP12) in neointimal SMCs. FKBP12 is the intracellular receptor for the makrolid sirolimus, an effective inhibitor of the mTORC1 complex. Our discovery provided a rationale for the use of sirolimus in prevention of restenosis in patients with coronary stent placement. Likewise, both placement of sirolimus-eluting stents and systemic treatment with sirolimus resulted in significant reductions of the risk of restenosis. Furthermore, we described the upregulation of a progenitor cell-associated gene expression pattern in human neointima from coronary in-stent restenosis such as the induction of the SDF-1 receptor CXCR-4 or the G-CSF receptor supporting the notion, that recruitment of bone marrow-derived progenitor cells to the site of vascular injury plays a role in neointima formation.
CBF, Medizinische Klinik II, Kardiologie und Pulmologie
Forschung & Lehre