Angiotensin Type I Receptor Blockade In Conjunction With Enhanced Akt Activation Restores Coronary Collateral Growth In The Metabolic Syndrome
Cardiovascular System & Cardiology; coronary artery occlusion; endothelial-cells; inhibition; ischemia-induced angiogenesis; kinase; mediated angiogenesis; nitric-oxide synthase; pathway; phosphorylation; Physiology; rat; smooth-muscle-cells; transient
Jadhav R, Dodd T, Smith E, Bailey E, DeLucia AL, Russell JC, Madison R, Potter B, Walsh K, Jo H, Rocic P. Angiotensin type I receptor blockade in conjunction with enhanced Akt activation restores coronary collateral growth in the metabolic syndrome. Am J Physiol Heart Circ Physiol 300: H1938-H1949, 2011. First published February 18, 2011; doi:10.1152/ajpheart.00282.2010.-We have previously demonstrated that Akt was required for repetitive ischemia (RI)-induced coronary collateral growth (CCG) in healthy rats but was not activated by RI in the metabolic syndrome (JCR:LA-cp rats) where CCG was impaired. Here we hypothesized that failure of angiotensin type I receptor (AT(1)R) blockers to restore Akt activation is a key determinant of their inability to completely restore CCG in the metabolic syndrome. Therefore, we investigated whether adenovirus-mediated delivery of constitutively active Akt (MyrAkt-Adv.) in conjunction with AT(1)R blockade (candesartan) was able to restore RI-induced CCG in JCR:LA-cp rats. Successful myocardial MyrAkt-Adv delivery was confirmed by a >80% transduction efficiency and an approximately fourfold increase in Akt expression and activation. CCG was assessed by myocardial blood flow measurements in the normal and collateral-dependent zones. MyrAkt-Adv alone significantly increased RI-induced CCG in JCR:LA-cp rats (similar to 30%), but it completely restored CCG in conjunction with administration of candesartan. In contrast, dominant negative Akt (DN-Akt-Adv) reversed the beneficial effect of candesartan on CCG in JCR:LA-cp rats. We conclude that optimal restoration of coronary collateral growth in JCR:LA-cp rats requires a combination of AT(1)R blockade with constitutive Akt activation. These findings may carry implications for metabolic syndrome patients in need of coronary revascularization.
Jadhav R; Dodd T; Smith E; Bailey E; DeLucia A L; Russell J C; Madison R; Potter B; Walsh K; Jo H J; Rocic P
American Journal of Physiology-Heart and Circulatory Physiology
2011
2011-05
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1152/ajpheart.00282.2010" target="_blank" rel="noreferrer noopener">10.1152/ajpheart.00282.2010</a>
Induced Vascular Progenitor Cells Derived From Endothelial Cells Stimulate Coronary Collateral Growth
Cardiovascular System & Cardiology; Collateral circulation
Yin L Y; Ohanyan V; Pung Y F; Delucia A L; Bailey E; Enrick M; Stevanov K; Kolz C L; Guarini G; Chilian W
Circulation
2011
2011-11
Journal Article
n/a
J-LEAPS vaccines initiate murine Th1 responses by activating dendritic cells.
*Antigen Presentation; Adoptive Transfer; Animals; Cells; Cultured; Dendritic Cells/*immunology; Epitopes; Female; gag Gene Products; Herpes Simplex/immunology/prevention & control; Herpesvirus 1; Human Immunodeficiency Virus/immunology; Human/immunology; Inbred A; Inbred C57BL; Interferon-gamma/immunology; Interleukin-12/immunology; Mice; T-Lymphocyte/immunology; Th1 Cells/*immunology; Viral Envelope Proteins/immunology; Viral Vaccines/*immunology
The Ligand Epitope Antigen Presentation System (LEAPS) converts a peptide containing a T cell epitope as small as 8 amino acids into an immunogen and directs the nature of the subsequent response. Tandem synthesis of the J peptide (a peptide from the beta-2-microglobulin) with peptides of 15 or 30 amino acids from HSV-1 or HIV made them immunogenic and promoted Th1 immune responses. Immunization of A/J or C57BL/6 mice with J-LEAPS heteroconjugates containing an epitope from the HSV-1 glycoprotein D (JgD) or an epitope from the HIV gag protein (JH) emulsified with Seppic ISA51 induced increased levels of IL-12p70 by day 3 and increased levels of interferon gamma (IFN-gamma) on days 10 and 24. Interestingly, levels of IL-10, TNF-alpha, and IL-6 did not change. Neither the H nor the gD peptides alone elicited responses and only weak responses followed immunization with the J peptide. Bone marrow (BM) cells became CD86 and CD11c positive within 48 h of treatment with JgD or JH. JH or JgD treatment promoted
Taylor P R; Koski G K; Paustian C C; Bailey E; Cohen P A; Moore F B-G; Zimmerman D H; Rosenthal K S
Vaccine
2010
2010-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.vaccine.2010.06.043" target="_blank" rel="noreferrer noopener">10.1016/j.vaccine.2010.06.043</a>
J-LEAPS Vaccines Mature Mouse Bone Marrow Cells to Dendritic Cells-1 (DC1) which can Deliver Protective Immunity
Immunology
Taylor P; Koski G; Bailey E; Zimmerman D; Rosenthal K S
Clinical Immunology
2010
2010
Journal Article
<a href="http://doi.org/10.1016/j.clim.2010.03.098" target="_blank" rel="noreferrer noopener">10.1016/j.clim.2010.03.098</a>
Nonsteroidal Anti-inflammatory Drugs, Indomethacin And Aspirin, Inhibit Herpes Simplex Virus Replication And Block Activation Of Nuclear Factor-kappab
Pharmacology & Pharmacy; Virology
Faith S A; Bailey E; Docherty J J
Antiviral Research
2006
2006-05
Journal Article or Conference Abstract Publication
n/a