| Περίληψη: | Atherosclerotic cardiovascular disease is the largest underlying cause of death and disability in the world, leading to the formation of plaques in the innermost layer of the arterial wall. Plaques can ultimately rupture or erode, causing thrombosis, decreasing partly or fully the blood flow. The extracellular matrix (ECM) is critical for all aspects of vascular pathobiology. It is mainly composed by collagens, elastic fibers, hyaluronan (HA), proteoglycans (PGs) decorated with glycosaminoglycans (GAGs) such as chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS), heparin and a variety of glycoproteins. The vulnerable plaques usually have a large lipid and necrotic core, are rich in inflammation and covered by a thin fibrous cap, that is accompanied by a unique ECM signature (with permanent synthesis & degradation).
Serglycin (SRGN) is a PG whose protein core can be decorated with different types of glycosaminoglycans, dictating in turn its action. It is mainly expressed in cells of the hematopoietic lineage (neutrophils, lymphocytes, monocytes, macrophages, platelets, megakaryocytes, mast cells), as well as in endothelial and smooth muscle cells. SRGN is a structural and functional chameleon, with radically different properties depending on its exact cellular and immunological context.
This MSc Thesis will focus on the role of SRGN in atherosclerosis, using human samples and in vitro mechanistic atherosclerosis models.
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