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>
Gene Expression Profiling Of Microglia Infected By A Highly Neurovirulent Murine Leukemia Virus: Implications For Neuropathogenesis
arrays; cells; central-nervous-system; endoplasmic-reticulum stress; env gene; envelope protein; induced spongiform neurodegeneration; mice; motor neuron disease; oligonucleotide; retrovirus; Virology
Dimcheff D E; Volkert L G; Li Y; DeLucia A L; Lynch W P
Retrovirology
2006
2006-05
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1186/1742-4690-3-26" target="_blank" rel="noreferrer noopener">10.1186/1742-4690-3-26</a>
The plant lignan 3-O-methyl-nordihydroguaiaretic acid induces apoptosis in human papilloma virus-positive cervical cancer cells by stabilizing p53 tumor suppressor protein
Nutrition & Dietetics
Allen K L; DeLucia A L
Journal of Nutrition
2003
2003-11
Journal Article or Conference Abstract Publication
n/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
Resveratrol inhibition of herpes simplex virus replication.
Animals; Antiviral Agents/*pharmacology/toxicity; Cell Cycle/drug effects; Cell Line; Cercopithecus aethiops; Herpesvirus 1; Herpesvirus 2; Human/*drug effects/physiology; Humans; Immediate-Early Proteins/antagonists & inhibitors/biosynthesis; Mice; Resveratrol; Stilbenes/*pharmacology/toxicity; Vero Cells; Virus Latency/drug effects/physiology; Virus Replication/*drug effects/physiology
Resveratrol, a phytoalexin, was found to inhibit herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) replication in a dose-dependent, reversible manner. The observed reduction in virus yield was not caused by the direct inactivation of HSV by resveratrol nor inhibition of virus attachment to the cell. The chemical did, however, target an early event in the virus replication cycle since it was most effective when added within 1 h of cell infection, less effective if addition was delayed until 6 h post-infection and not effective if added 9 h post-infection. Resveratrol was also found to delay the cell cycle at S-G2-M interphase, inhibit reactivation of virus from latently-infected neurons and reduce the amount of ICP-4, a major immediate early viral regulatory protein, that is produced when compared to controls. These results suggest that a critical early event in the viral replication cycle, that has a compensatory cellular counterpart, is being adversely affected.
Docherty J J; Fu M M; Stiffler B S; Limperos R J; Pokabla C M; DeLucia A L
Antiviral research
1999
1999-10
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/s0166-3542(99)00042-x" target="_blank" rel="noreferrer noopener">10.1016/s0166-3542(99)00042-x</a>
Inhibition of human papillomavirus type 16 gene expression by nordihydroguaiaretic acid plant lignan derivatives.
Antiviral Agents/*pharmacology; Cultured; Female; Gene Expression Regulation; Genetic/drug effects; HIV Long Terminal Repeat/drug effects; Humans; Lignans/chemistry/pharmacology; Masoprocol/*analogs & derivatives/*pharmacology; Papillomaviridae/*genetics; Promoter Regions; Simian virus 40/genetics; Tumor Cells; Viral/*drug effects
Several methylated derivatives of a plant lignan, nordihydroguaiaretic acid (NDGA) were found to be potent anti-viral agents by suppressing Sp1 regulated transcription within the sexually transmitted viruses human immunodeficiency virus (HIV) and herpes simplex virus (HSV). A prominent Sp1 DNA binding site within many human papillomavirus (HPV) promoters has been noted to play an active role in HPV gene expression. In this report it is shown that the three NDGA derivatives, Mal.4, M(4)N, and tetra-acetyl NDGA can also inhibit gene expression from the early promoter P(97) of HPV16. The drug activity on gene expression was measured after DNA transfection of recombinant vector constructs linking the viral promoter and enhancer elements to the luciferase reporter gene. Using the specific luciferase activity as the indicator of gene expression, Mal.4 and M(4)N were found to be active in a dose dependent manner that is in the same range of concentrations reported for the promoters of HIV, HSV, and simian virus 40 (SV40) while tetra-acetyl NDGA was much more active in suppression of the HPV P(97) promoter activity than Mal.4 and M(4)N. The drugs showed limited to no effect on gene expression driven by the adenovirus major late promoter and the cytomegalovirus (CMV) promoter. Hence, such drug derivatives may be significant in the therapy of papillomavirus infections and their associated induced human cancers.
Craigo J; Callahan M; Huang R C; DeLucia A L
Antiviral research
2000
2000-07
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/s0166-3542(00)00089-9" target="_blank" rel="noreferrer noopener">10.1016/s0166-3542(00)00089-9</a>