Atherosclerosis is a chronic inflammatory disease whose late-stage clinical complications including myocardial infarction (heart attack) and stroke, are the leading causes of death worldwide. Clinical trials of anti-inflammatory therapies yield only modest benefits, underscoring the need for alternative approaches to enhance atherosclerotic plaque stability. One potential approach is to target transforming growth factor beta (TGFβ) signaling which has been proposed to play a critical role in atherosclerosis development and late-stage pathogenesis.<\/p>\n
Whereas single-cell RNA sequencing and Myh11-smooth muscle cell (SMC) lineage tracing studies by our laboratory and others have provided extensive evidence that SMC-derived cells within atherosclerotic lesions display a wide range of distinct phenotypes, including a subset of Myh11+ medial cells that activate stem cell antigen-1 (Sca1), the role of Sca1 in atherosclerosis development remains unknown. Using unique Myh11 Sca1 dual recombinase and knockout mouse models, we aim to identify the functional role and mechanisms of Sca1 in atherosclerosis development and late-stage pathogenesis. We are testing the hypothesis that Sca1 has a major role in atherosclerosis development and late-stage pathological events by negatively regulating TGFβ signaling. In our novel SR-BIΔCT\/ΔCT<\/sup>\/Ldlr-\/-<\/sup><\/em> mouse model of spontaneous plaque rupture, heart attack and stroke, we seek to determine whether Sca1 inhibition alters TGFβ signaling and improves survival due to reduced heart attack and stroke. Another major focus of our laboratory is to identify novel mechanisms and factors that lead to vascular calcification with a long-term goal is to prevent and\/or reverse vascular calcification without compromising bone health.<\/p>\n","protected":false},"featured_media":1735368,"template":"","meta":{"_acf_changed":false,"inline_featured_image":false,"_links_to":"","_links_to_target":""},"otheraff":[2486],"phd-degree":[],"primary":[2335],"research-discipline":[2487,2492,2512,2503,2490],"research-opportunity":[],"training-grant":[],"class_list":["post-1734900","faculty-listing","type-faculty-listing","status-publish","has-post-thumbnail","hentry","otheraff-rfd-non-faculty","primary-molecular-physiology-and-biological-physics","research-discipline-biochemistry","research-discipline-bioinformatics-and-genomics","research-discipline-cardiovascular-biology","research-discipline-immunology","research-discipline-molecular-biology"],"acf":[],"yoast_head":"\n