Posts Tagged: mice

New Insights Into the Role of mTOR Signaling in the Cardiovascular System

New Insights Into the Role of mTOR Signaling in the Cardiovascular System

Sebastiano Sciarretta, Maurizio Forte, Giacomo Frati, Junichi Sadoshima

Schematic overview of the upstream signaling modulators of mTORC1 (mTOR [mechanistic target of rapamycin] complex 1) and mTORC2. Signaling network regulating mTORC1 and mTORC2 activity. Arrows indicate the effects of different conditions or cellular events on mTOR activity. Red arrows represent maladaptive input signals, whereas green arrows represent adaptive input signals. Akt indicates protein kinase B; AMPK, adenosine monophosphate activated protein kinase; CASTOR 1/2, cellular arginine sensor for mTORC1 1/2; ERK1/2, extracellular signal–regulated kinase 1/2; GATOR 1/2, GAP activity toward Rags 1/2; GSK-3β, glycogen synthase kinase-3β; IKKβ, inhibitor of NF-κB kinase-β; PI3K, phosphoinositide 3 kinase; PRAS40, proline-rich Akt substrate 40; Rag, Ras-related GTPase; Raptor, regulatory-associated protein of mTOR; REDD1, regulated in development and DNA damage responses 1; Rheb, Ras homolog enriched in brain; and TSC1/2, tuberous sclerosis protein 1/2. [Powerpoint File]

High-Density Lipoprotein and Atherosclerosis Regression: Evidence From Preclinical and Clinical Studies

High-Density Lipoprotein and Atherosclerosis Regression: Evidence From Preclinical and Clinical Studies

Jonathan E. Feig*, Bernd Hewing*, Jonathan D. Smith, Stanley L. Hazen, Edward A. Fisher

The promotion of atherosclerosis regression by high-density lipoprotein (HDL) in an aortic transplantation mouse model. Monocytes are recruited into plaques and become macrophages. These macrophages become activated, cholesterol-laden foam cells, as a result of ingesting normal and modified apolipoprotein B–containing lipoproteins and are retained in the plaque. On the basis of in vitro and preclinical studies, we found that the recently recognized ways in which HDL can contribute to plaque regression include reduced monocyte recruitment because of reduced leukocytosis or endothelial cell adhesion molecule expression, the stimulation of C-C chemokine receptor type 7 (CCR7) expression by the promotion of cholesterol efflux from foam cells, which results in emigration of macrophages to lymphoid tissue and to the systemic circulation, and the stimulation of the STAT6 pathway to polarize macrophages to the M2 state, as indicated by the increase in the markers mannose receptor (MR), interleukin (IL)-10, and arginase I (Arg I). As tissue repairs cells, M2 macrophages also exhibit enhanced efferocytosis (disposal) of apoptotic cells. See text for details and for additional mechanisms. LDL indicates low-density lipoprotein. [Powerpoint File]

Genetic Basis of Atherosclerosis: Insights From Mice and Humans

Genetic Basis of Atherosclerosis: Insights From Mice and Humans

Ioannis M. Stylianou, Robert C. Bauer, Muredach P. Reilly, Daniel J. Rader

Phenotypic progression of atherosclerosis in mouse and humans. A, Approximate progression of observable atherosclerosis in mouse models, noting that double knockouts (DKOs) on either the Ldlr−/− or Apoe−/− backgrounds can have decrease as well as increased atherosclerosis. B, An approximate illustration of clinical characterization of atherosclerosis in humans. [Powerpoint File]