Characterization and clinical outcomes of drug-eluting in-stent restenosis.

BACKGROUND: The best therapeutic alternative for patients suffering from in-stent restenosis after drug-eluting stent implantation remains to be elucidated. OBJECTIVE: To characterize the pattern, treatment and outcomes of DES-related in-stent restenosis in patients treated at our institution. METHODS: We determined the incidence and major adverse clinical events in 71 consecutive patients with DES failure among 2473 patients who were treated with 2548 drug-eluting stents between 2004 and 2007. We analyzed the clinical data, procedural parameters and clinical outcomes. RESULTS: The type and number of stents implanted were as follows: Cypher (n = 1808), Endeavor (421) and Taxus (319); of these, 53 (2.9%), 10 (2.4%), and 8 (2.5%) patients respectively presented with restenosis. The mean time to restenosis was 11.3 +/- 9.9 months. Patients' mean age was 65 +/- 11 years; 75% were male, and 68% had diabetes mellitus. Unstable angina was the clinical presentation in 52 (73%). At 6 months, 3 patients had developed myocardial infarction (4.2%), repeat restenosis at follow-up was diagnosed in 8 patients (11.3%), the overall major adverse clinical events rate was 18.3% (13 patients), and 2 patients died (2.8%). CONCLUSIONS: Drug-eluting stent-related restenosis is relatively infrequent but remains a clinical challenge. It occurs more frequently in complex lesion subsets, but the overall intermediate-term prognosis is tolerable.

Activation of GRP78 on endothelial cell membranes by an ADAM15-derived peptide induces angiogenesis.

Impaired angiogenesis is one of the features of ischemic diseases. We have previously identified, by screening a phage display peptide library, a peptide that induces angiogenesis in endothelial cells under hypoxic conditions by binding the cell's membrane heat shock protein GRP78. Protein data base search identified 4 amino acids (HWRR) of that synthetic peptide present on the ADAM15 metalloprotease domain, a protein considered to be involved in neovascularization. Three peptides were synthesized according to the ADAM15 sequence placing HWRR at different positions. Peptide ADoPep1 exhibited significant angiogenic properties under hypoxic conditions as determined by cell proliferation, migration and tube formation. In a mouse hind limb ischemia model, a single injection of the peptide restored blood perfusion. The identified peptide was found to activate GRP78 on endothelial cell membrane and siRNA directed against the GRP78 mRNA interfered with induction of angiogenesis by the peptide. The peptide binding induced a decrease in heat shock protein GRP78 that is overexpressed under hypoxic conditions. The mechanism of peptide-induced angiogenic activity involves inhibition of apoptosis as well as increased Akt phosphorylation and ERK 1/2 activation. The peptide did not induce VEGF receptor-2 protein synthesis and phosphorylation, suggesting a VEGF-independent mechanism of angiogenesis.