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Michael Autieri, PhDMichael Autieri , PhD

 

Professor, Physiology

Professor, Cardiovascular Research Center

Professor, Sol Sherry Thrombosis Research Center

Telephone:  215-707-1751

Fax:  215-707-5737

Office: MERB 1050

Email: mautieri@temple.edu

 

Department of Physiology

Cardiovascular Research Center

Sol Sherry Thrombosis Research Center

 

Educational Background:

 

PhD, Hahnemann University, Philadelphia, PA

 

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Research Interests:

 

The long-term focus of our research program is the identification and characterization of proteins which play a role in regulation of vascular inflammation. We have two distinct, but related areas of investigation: 1- inhibition of vascular occlusive diseases such as atherosclerosis, and; 2- promotion of angiogenesis, the growth of new blood vessels, to treat peripheral vascular disease by anti-inflammatory factors. The following are summaries from each NIH grant.

Mechanisms of Th2 interleukin-driven angiogenesis. The overall goal of this application is to determine how Interleukin-19 regulates angiogenesis. IL-19 is a newly described Th2, (T regulatory) anti-inflammatory interleukin which until our work, had been ascribed to be inflammatory cell-specific. We remain the only laboratory to investigate a role for this Interleukin in vascular biology, particularly with respect to EC and VSMC pathophysiology. Both inflammatory and anti-inflammatory cytokines participate in wound healing and neo-vascularization, but the role of anti-inflammatory cytokines in angiogenesis and the cross-talk between these processes remain under characterized. In contrast to our previous work indicating that IL-19 suppresses vascular smooth muscle cells (VSMC) migration and proliferation, we have recently reported the surprising finding that IL-19 has potent pro-angiogenic effects on human endothelial cells (EC). IL-19 is not detected in normal EC but is expressed in EC in capillaries in human angiogenic tissue. IL-19 is mitogenic and chemotactic for EC, promotes cell spreading, and activates MAPK and Rac1. IL-19 promotes microvessel formation in aortic rings, and PECAM1-positive microvessels in vivo. IL-19 can induce angiogenic gene expression in EC. IL-19 effects are independent of VEGF and bFGF, as neither can induce IL-19 expression, and IL-19 cannot induce expression of either. Neutralization of bFGF and VEGF does not effect IL-19 activity, suggesting a novel, Th2-induced pathway to stimulate EC activation and angiogenesis. IL-19 can polarize human macrophage to the M2, “wound healing” phenotype, and induce angiogenic gene expression in macrophage. IL-19 expression and function is reciprocal to and regulates the pro-inflammatory anti-angiogenic cytokine IL-12. These preliminary and published data have driven the hypothesis that IL-19 is a novel vasculogenic cytokine with multiple effector cells. This work is potentially paradigm-changing as it will implicate a Th2 interleukin as a novel anti-inflammatory, pro-vasculogenic cytokine expressed by inflamed resident vascular cells to promote neovascularization.

Interleukin-19 inhibits Atherosclerosis by Diverse Mechanisms. The overall goals of this application are to demonstrate that Interleukin-19 (IL-19), a Th2 anti-inflammatory interleukin, can attenuate atherosclerosis, and identify the potential mechanisms of this inhibition. IL-19 is a newly described Th2, (T regulatory) anti-inflammatory interleukin which until our work, had been ascribed to be inflammatory cell-specific. We remain the only laboratory to investigate a role for this interleukin in vascular biology, particularly with respect to EC and VSMC pathophysiology, and to demonstrate molecular mechanisms for these effects. We previously reported that; 1- IL-19 is not detectible in normal artery, but is induced in EC and VSMC in human atherosclerotic lesions; 2- addition of IL-19 to VSMC reduces their migration, proliferation, and abundance of proliferative and inflammatory proteins; 3- IL-19 does NOT inhibit NF-B, but does reduce the stability of inflammatory and proliferative mRNA transcripts in an HuR-dependent manner; 4- IL-19 induces expression of the vascular and cyto-protective protein Hemeoxygenase-1 (HO-1), and reduces apoptosis induced by vascular reactive oxygen species (ROS) in an HO-1 dependent manner. In this application we present preliminary data showing that addition of recombinant IL-19 to LDLR-/- mice fed an atherogenic diet significantly and dramatically decreases atherosclerotic plaque, and IL-19-/- mice have an exacerbated response to ligation injury. Based on published and preliminary data, we hypothesize that there are multiple, pleiotropic mechanisms for these protective effect. This application is potentially paradigm-changing as it will implicate a Th2 interleukin as an endogenous cytokine expressed by inflamed vascular cells with multiple autocrine and paracrine dampening effects. It will identify novel molecular mechanisms and targets of anti-inflammatory pathways in these cells.

 

autieri athlersclerosis research

 


IL-19 inhibits experimental atherosclerosis. Atherosclerosis-prone mice fed a high-fat diet treated with saline control or recombinant IL-19. Red areas indicate lipid-rich plaque

 

 

 

 

 



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PUBMED PUBLICATIONS :


Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

24814101. Ellison S, Gabunia K, Richards JM, Kelemen SE, England RN, Rudic D, Azuma YT, Munroy MA, Eguchi S, Autieri MV, IL-19 reduces ligation-mediated neointimal hyperplasia by reducing vascular smooth muscle cell activation. Am J Pathol 184:7(2134-43)2014 Jul

23950143. Ellison S, Gabunia K, Kelemen SE, England RN, Scalia R, Richards JM, Orr AW, Traylor JG Jr, Rogers T, Cornwell W, Berglund LM, Goncalves I, Gomez MF, Autieri MV, Attenuation of experimental atherosclerosis by interleukin-19. Arterioscler Thromb Vasc Biol 33:10(2316-24)2013 Oct

23657571. Autieri MV, Increasing our IQ of vascular smooth muscle cell migration with IQGAP1. Focus on "IQGAP1 links PDGF receptor- signal to focal adhesions involved in vascular smooth muscle cell migration: role in neointimal formation after vascular injury". Am J Physiol Cell Physiol 305:6(C579-80)2013 Sep 15

23596173. England RN, Preston KJ, Scalia R, Autieri MV, Interleukin-19 decreases leukocyte-endothelial cell interactions by reduction in endothelial cell adhesion molecule mRNA stability. Am J Physiol Cell Physiol 305:3(C255-65)2013 Aug 1

22844641. England RN, Autieri MV, Anti-inflammatory effects of interleukin-19 in vascular disease. Int J Inflam 2012:(253583)2012

22158875. Gabunia K, Ellison SP, Singh H, Datta P, Kelemen SE, Rizzo V, Autieri MV, Interleukin-19 (IL-19) induces heme oxygenase-1 (HO-1) expression and decreases reactive oxygen species in human vascular smooth muscle cells. J Biol Chem 287:4(2477-84)2012 Jan 20

21862018. Sommerville LJ, Kelemen SE, Ellison SP, England RN, Autieri MV, Increased atherosclerosis and vascular smooth muscle cell activation in AIF-1 transgenic mice fed a high-fat diet. Atherosclerosis 220:1(45-52)2012 Jan

21357274. Takaguri A, Kimura K, Hinoki A, Bourne AM, Autieri MV, Eguchi S, A disintegrin and metalloprotease 17 mediates neointimal hyperplasia in vasculature. Hypertension 57:4(841-5)2011 Apr

21209363. Gabunia K, Jain S, England RN, Autieri MV, Anti-inflammatory cytokine interleukin-19 inhibits smooth muscle cell migration and activation of cytoskeletal regulators of VSMC motility. Am J Physiol Cell Physiol 300:4(C896-906)2011 Apr

20966397. Jain S, Gabunia K, Kelemen SE, Panetti TS, Autieri MV, The anti-inflammatory cytokine interleukin 19 is expressed by and angiogenic for human endothelial cells. Arterioscler Thromb Vasc Biol 31:1(167-75)2011 Jan

20451530. Cuneo AA, Herrick D, Autieri MV, Il-19 reduces VSMC activation by regulation of mRNA regulatory factor HuR and reduction of mRNA stability. J Mol Cell Cardiol 49:4(647-54)2010 Oct

19901155. Hinoki A, Kimura K, Higuchi S, Eguchi K, Takaguri A, Ishimaru K, Frank GD, Gerthoffer WT, Sommerville LJ, Autieri MV, Eguchi S, p21-activated kinase 1 participates in vascular remodeling in vitro and in vivo. Hypertension 55:1(161-5)2010 Jan

19601851. Cuneo AA, Autieri MV, Expression and function of anti-inflammatory interleukins: the other side of the vascular response to injury. Curr Vasc Pharmacol 7:3(267-76)2009 Jul

19095998. Suzuki H, Kimura K, Shirai H, Eguchi K, Higuchi S, Hinoki A, Ishimaru K, Brailoiu E, Dhanasekaran DN, Stemmle LN, Fields TA, Frank GD, Autieri MV, Eguchi S, Endothelial nitric oxide synthase inhibits G12/13 and rho-kinase activated by the angiotensin II type-1 receptor: implication in vascular migration. Arterioscler Thromb Vasc Biol 29:2(217-24)2009 Feb

18779232. Sommerville LJ, Xing C, Kelemen SE, Eguchi S, Autieri MV, Inhibition of allograft inflammatory factor-1 expression reduces development of neointimal hyperplasia and p38 kinase activity. Cardiovasc Res 81:1(206-15)2009 Jan 1

18669613. Tian Y, Sommerville LJ, Cuneo A, Kelemen SE, Autieri MV, Expression and suppressive effects of interleukin-19 on vascular smooth muscle cell pathophysiology and development of intimal hyperplasia. Am J Pathol 173:3(901-9)2008 Sep

17991871. Sommerville LJ, Kelemen SE, Autieri MV, Increased smooth muscle cell activation and neointima formation in response to injury in AIF-1 transgenic mice. Arterioscler Thromb Vasc Biol 28:1(47-53)2008 Jan

16291819. Tian Y, Kelemen SE, Autieri MV, Inhibition of AIF-1 expression by constitutive siRNA expression reduces macrophage migration, proliferation, and signal transduction initiated by atherogenic stimuli. Am J Physiol Cell Physiol 290:4(C1083-91)2006 Apr

16049345. Kelemen SE, Autieri MV, Expression of allograft inflammatory factor-1 in T lymphocytes: a role in T-lymphocyte activation and proliferative arteriopathies. Am J Pathol 167:2(619-26)2005 Aug

15922740. Autieri MV, Chen X, The ability of AIF-1 to activate human vascular smooth muscle cells is lost by mutations in the EF-hand calcium-binding region. Exp Cell Res 307:1(204-11)2005 Jul 1

15737749. Kelemen SF, Eisen HJ, Autieri MV, Expression of the FAST-1 transcription factor in coronary artery transplant vasculopathy and activated vascular smooth muscle cells. J Heart Lung Transplant 24:3(246-50)2005 Mar

15385271. Chen X, Kelemen SE, Autieri MV, Expression of granulocyte colony-stimulating factor is induced in injured rat carotid arteries and mediates vascular smooth muscle cell migration. Am J Physiol Cell Physiol 288:1(C81-8)2005 Jan

15320847. Autieri MV, Allograft-induced proliferation of vascular smooth muscle cells: potential targets for treating transplant vasculopathy. Curr Vasc Pharmacol 1:1(1-9)2003 Mar

15257047. Autieri MV, Kelemen SE, Gaughan JP, Eisen HJ, Early growth responsive gene (Egr)-1 expression correlates with cardiac allograft rejection. Transplantation 78:1(107-11)2004 Jul 15

15117732. Chen X, Kelemen SE, Autieri MV, AIF-1 expression modulates proliferation of human vascular smooth muscle cells by autocrine expression of G-CSF. Arterioscler Thromb Vasc Biol 24:7(1217-22)2004 Jul

15098065. Autieri MV, Antiproliferative effects of immunosuppressant drugs on vascular smooth muscle cells: an additional advantage for attenuating transplant vasculopathy. Drug News Perspect 17:2(110-6)2004 Mar

15010287. Autieri MV, Inducible expression of the signal transduction protein 14-3-3gamma in injured arteries and stimulated human vascular smooth muscle cells. Exp Mol Pathol 76:2(99-107)2004 Apr

12819813. Autieri MV, Regulating the regulators: transcription factors as targets for attenuating proliferative arteriopathies. Drug News Perspect 16:3(149-58)2003 Apr

12714565. Autieri MV, Kelemen SE, Wendt KW, AIF-1 is an actin-polymerizing and Rac1-activating protein that promotes vascular smooth muscle cell migration. Circ Res 92:10(1107-14)2003 May 30

12390951. Autieri MV, Kelemen S, Thomas BA, Feller ED, Goldman BI, Eisen HJ, Allograft inflammatory factor-1 expression correlates with cardiac rejection and development of cardiac allograft vasculopathy. Circulation 106:17(2218-23)2002 Oct 22

11557666. Autieri MV, Carbone CM, Overexpression of allograft inflammatory factor-1 promotes proliferation of vascular smooth muscle cells by cell cycle deregulation. Arterioscler Thromb Vasc Biol 21:9(1421-6)2001 Sep

11401522. Autieri MV, Expression of anaphase-promoting complex 5 in balloon angioplasty-injured rat carotid arteries and mitogen-stimulated human vascular smooth muscle cells. Biochem Biophys Res Commun 282:3(723-8)2001 Apr 6

11250347. Autieri MV, Carbone CJ, Eisen H, The growth enhancing effects of allograft inflammatory Factor-1 (AIF-1) in VSMC are dose-dependent and mediated by its ability to bind calcium. J Heart Lung Transplant 20:2(198)2001 Feb

10894811. Autieri MV, Carbone C, Mu A, Expression of allograft inflammatory factor-1 is a marker of activated human vascular smooth muscle cells and arterial injury. Arterioscler Thromb Vasc Biol 20:7(1737-44)2000 Jul

10433554. Autieri MV, Carbone CJ, 14-3-3Gamma interacts with and is phosphorylated by multiple protein kinase C isoforms in PDGF-stimulated human vascular smooth muscle cells. DNA Cell Biol 18:7(555-64)1999 Jul

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Trainees:

 

Dr. Autieri Lab is located MERB 1081     215-707-2427  

 

Postdoctoral Fellows         

 Khatuna Gabunia         khatuna.gabunia@temple.edu                                                                                

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laboratory personnel:

 

Sheri Kelmen

Lab Manager - Autieri Lab

T:  215-707-3170

F:  215-707-5737

Email address: sheri.kelemen@temple.edu

 

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