Research Project
10333044
Project abstract Atherosclerotic cardiovascular disease (CVD) is the leading cause of death in the industrialized world. Failed resolution of a chronic inflammatory response is an important driving force in the progression of atherosclerosis. Resolution is mediated by the critical balance between specialized pro-resolving mediators (SPMs) such as lipoxins and resolvins and pro-inflammatory factors like leukotrienes (LTs) and prostaglandins (PGs). work SPMs processes plaques and b) mechanisms associated with the protective actions of SPMs in atherosclerosis. Therefore, the overall objective of this administrative supplement is for Masharh Lipscomb to understand new mechanisms of dysregulated resolution in atherosclerosis and to harness new SPM signaling pathways towards a novel treatment strategy. Cellular senescence is an irreversible cell cycle arrest that leads to a highly pro-inflammatory phenotype called the senescence- Previous from our lab and others suggest that SPMs are defectively synthesized in plaques and that restoration of prevents atherosclerosis progression in mice. Gaps remain in our understanding as to a) what cellular derange the synthesis of SPMs in associated secretory phenotype (SASP). We and other observed that senescent cells accumulate in atherosclerosis cleared and a major goal of Masharh work is to uncover why these harmful cells cannot be readily and neutralized.We postulate that the SASP drives an increase in key ?don't' eat me? signals that coax macrophages to limit clearance. This administrative supplement will allow Masharh Lipscomb to learn new techniques while also increasing the quality of the deliverables on the parent grant.
