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Appendix - CNIC

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SCIENTIFIC REPORT ´09<br />

> RESEARCH INTEREST<br />

Accumulation of blood-borne leukocytes and their<br />

proliferation within the atherosclerotic plaque is a hallmark<br />

of atherosclerosis. During disease progression, inflammatory<br />

mediators produced by activated neointimal macrophages<br />

and lymphocytes induce the proliferation of vascular smooth<br />

muscle cells (VSMCs) and their migration towards the<br />

growing lesion. Moreover, accumulation of non-cellular<br />

material such as modified lipids and extracellular matrix<br />

components contribute to atheroma growth. Excessive<br />

cellular hyperplasia is also a feature of restenosis, the major<br />

limitation to the long-term success of revascularization via<br />

stent placement.<br />

Our research addresses the cellular, molecular and genetic<br />

mechanisms that underlie the development of atherosclerosis<br />

and restenosis, with particular emphasis on the role of cellcycle<br />

regulatory factors, as well as the identification of<br />

biomarkers of these diseases. Our experimental strategy<br />

4 Atherothrombosis and Cardiovascular Imaging<br />

Molecular and genetic<br />

cardiovascular pathophysiology<br />

Head of Laboratory: Vicente Andrés García<br />

Postdoctoral Researchers: José María González Granado<br />

José Rivera Torres<br />

Laia Trigueros Motos<br />

Predoctoral Researchers: Pedro Molina Sánchez<br />

Carlos Silvestre Roig<br />

Technician: María Jesús Andrés Manzano<br />

involves a multifaceted approach that combines in vitro,<br />

cellular, animal and human studies and a variety of<br />

technologies including mouse genetic engineering,<br />

proteomics, transcriptomics, FRET, confocal microscopy, and<br />

yeast 2-hybrid screening.<br />

Specific projects in the lab include: 1) Generation and<br />

characterization of genetically-modified mice to investigate<br />

the role of candidate genes in atherosclerosis, including<br />

Cre/lox strategies to ablate genes specifically in cell types<br />

involved in atherosclerosis (VSMCs, endothelial cells and<br />

macrophages); 2) Studies of the consequences of single<br />

nucleotide polymorphisms in cell-cycle regulatory genes on<br />

human susceptibility to in-stent restenosis; and 3) Research<br />

into the role of the nuclear envelope in the regulation of<br />

signal transduction, gene expression and cell-cycle activity in<br />

cardiovascular disease and aging.<br />

Mechanisms of atherosclerosis<br />

59

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