![]() ![]() #2 Association of transthyretin Val122Ile variant with incident heart failure and mortality among Black Americans: insights from the regards studyġUniversity of Alabama at Birmingham, Birmingham, ALĤWeil Cornell Medical Center, New York, NY IGF1 potentially exerts its atheroprotective effect via this reduction in CXCL12 by reducing monocyte recruitment and by increasing ABCA1, thereby increasing cholesterol efflux capacity. Our results indicate that macrophage IGF1 reduces atherosclerosis and decreases CXCL12, a chemokine newly implicated in atheroprogression. We also found a 27% increase in cholesterol efflux in IGF1 (100 ng/mL) treated THP-1 cells with Apolipoprotein AI as a cholesterol acceptor. We loaded peritoneal macrophages with oxLDL to measure changes in cholesterol efflux and found that MF-IGF1 mice have a 42% increase in efflux. We found that peritoneal macrophages isolated from MF-IGF1 mice have a 2 fold increase in ABCA1 protein levels. IGF1 completely blocked oxidized low-density lipoprotein (oxLDL)-dependent increase of CXCL12 mRNA transcription (98% reduction, P<0.01) and IGF1 treatment reduced CXCL12 protein (56% decrease, P<0.001) in vitro.ĪTP-binding cassette transporter A1 (ABCA1) is the key cholesterol transporter mediating macrophage cholesterol efflux and CXCL12 reduces its expression. CXCL12 protein levels were reduced in plaque and peritoneal macrophages in MF-IGF1 mice. Monocyte recruitment was reduced by 70% in MF-IGF1 mice and was associated with a 27% reduction in circulating levels of CXC Chemokine Ligand 12 (CXCL12). Macrophage IGF1 overexpression downregulated plaque burden by 30%, reduced plaque macrophages by 47%, and promoted features of a stable plaque phenotype. We also assessed cholesterol efflux and foam cell formation in vivo and in vitro. We accelerated atherosclerotic development by feeding animal a high fat diet for three months. We hypothesized that increasing IGF1 levels strictly in macrophages will prevent atherosclerosis.Īfter breeding a novel macrophage-specific IGF1 overexpressing transgenic mouse to an Apoe -/- background (MF-IGF1 mice), we assessed atherosclerotic plaque burden, stability, and monocyte recruitment. Results of our previous in vitro experiments suggest that macrophages play a predominant role in mediating IGF1 effects in atherosclerotic plaque, but exact mechanisms remain unclear. IGF1 administration in ApoE deficient (Apoe -/-) mice fed a high fat diet reduced atherosclerosis and reduced plaque macrophages. Insulin Like Growth Factor I (IGF1) has been shown to reduce cardiovascular events. Press esc, or click the close the button to close this dialog box.1Tulane University School of Medicine, New Orleans, LAĢUniversity of Missouri System, Columbia, MOĪtherosclerosis is the leading cause of Cardiovascular Disease, which is still the global leader of mortality. ![]() Search (Combination + S): Shortcut for search page. Site Map (Combination + M): Shortcut for site map (footer agency) section of the page. Main Content (Combination + R): Shortcut for viewing the content section of the current page.įAQ (Combination + Q): Shortcut for FAQ page.Ĭontact (Combination + C): Shortcut for contact page or form inquiries.įeedback (Combination + K): Shortcut for feedback page. ![]() Home Page (Combination + H): Accessibility key for redirecting to homepage. ![]() Shortcut Keys Combination Activation Combination keys used for each browser.Ĭhrome for Linux press (Alt+Shift+shortcut_key)Ĭhrome for Windows press (Alt+shortcut_key)įor Firefox press (Alt+Shift+shortcut_key)įor Internet Explorer press (Alt+Shift+shortcut_key) then press (enter)Īccessibility Statement (Combination + 0): Statement page that will show the available accessibility keys. A guide to understanding and implementing Web Content Accessibility Guidelines 2.0 is available at: Compliance to these criteria is measured in three levels: A, AA, or AAA. There are testable success criteria for each guideline. WCAG 2.0 contains 12 guidelines organized under 4 principles: Perceivable, Operable, Understandable, and Robust (POUR for short). This certifies it as a stable and referenceable technical standard. WCAG 2.0 is also an international standard, ISO 40500. This website adopts the Web Content Accessibility Guidelines (WCAG 2.0) as the accessibility standard for all its related web development and services. ![]()
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