A genome wide association analysis in the GENDER study

Percutaneous coronary intervention (PCI) has become an effective therapy to treat coronary artery diseases. However, one of the major drawbacks of PCI is the occurrence of restenosis in 8 to 40% of all treated patients. The GENetic Determinants of Restenosis (GENDER) project was designed to study the association between genetic polymorphisims and clinical restenosis. The discovery of genetic variants associated to the occurrence of restenosis after PCI may provide a more tailored therapy and may serve as rationale for new antirestenotic therapies. So far, several candidate gene approaches had already been performed in the GENDER samples but a Genome Wide Association Scan (GWAS) was still lacking. Here, we present preliminary results from the GWAS we are currently carrying out in the GENDER population. (Neth Heart J 2009;17:262-4.

A genome wide association analysis in the GENDER study

Cardiolog

RP105, a Toll Like Receptor 4 (TLR4) homolog, moderates restenosis and outward remodeling

Vascular Surger

Annexin A5 prevents post-interventional accelerated atherosclerosis development in a dose-dependent fashion in mice

BACKGROUND: Activated cells in atherosclerotic lesions expose phosphatidylserine (PS) on their surface. Annexin A5 (AnxA5) binds to PS and is used for imaging atherosclerotic lesions. Recently, AnxA5 was shown to inhibit vascular inflammatory processes after vein grafting. Here, we report a therapeutic role for AnxA5 in post-interventional vascular remodeling in a mouse model mimicking percutaneous coronary intervention (PCI). METHODS AND RESULTS: Associations between the rs4833229 (OR=1.29 (CI 95%), p(allelic)=0.011) and rs6830321 (OR=1.35 (CI 95%), p(allelic)=0.003) SNPs in the AnxA5 gene and increased restenosis-risk in patients undergoing PCI were found in the GENDER study. To evaluate AnxA5 effects on post-interventional vascular remodeling and accelerated atherosclerosis development in vivo, hypercholesterolemic ApoE(-/-) mice underwent femoral arterial cuff placement to induce intimal thickening. Dose-dependent effects were investigated after 3days (effects on inflammation and leukocyte recruitment) or 14days (effects on remodeling) after cuff placement. Systemically administered AnxA5 in doses of 0.1, 0.3 and 1.0mg/kg compared to vehicle reduced early leukocyte and macrophage adherence up to 48.3% (p=0.001) and diminished atherosclerosis development by 71.2% (p=0.012) with a reduction in macrophage/foam cell presence. Moreover, it reduced the expression of the endoplasmic reticulum stress marker GRP78/BiP, indicating lower inflammatory activity of the cells present. CONCLUSIONS: AnxA5 SNPs could serve as markers for restenosis after PCI and AnxA5 therapeutically prevents vascular remodeling in a dose-dependent fashion, together indicating clinical potential for AnxA5 against post-interventional remodeling.Cardiolog

ANNEXIN A5 PREVENTS REACTIVE STENOSIS IN A DOSE-DEPENDENT FASHION: POTENTIAL FOR CLINICAL APPLICATION

Vascular Biology and Interventio

Systematic testing of literature reported genetic variation associated with restenosis after percutaneous coronary intervention: results of the genetic determinants of restenosis study

Pathophysiology, epidemiology and therapy of agein

Systematic Testing of Literature Reported Genetic Variation Associated with Coronary Restenosis: Results of the GENDER Study

Development and application of statistical models for medical scientific researc