Coexpression of VEGF and angiopoietin-1 promotes angiogenesis and cardiomyocyte proliferation reduces apoptosis in porcine myocardial infarction (MI) heart.

Abstract:

:VEGF and angiopoietin-1 (Ang1) are two major angiogenic factors being investigated for the treatment of myocardial infarction (MI). Targeting VEGF and Ang1 expression in the ischemic myocardium can increase their local therapeutic effects and reduce possible adverse effects. Adeno-associated viral vectors (AAVs) expressing cardiac-specific and hypoxia-inducible VEGF [AAV-myosin light chain-2v (MLC)VEGF] and Ang1 (AAV-MLCAng1) were coinjected (VEGF/Ang1 group) into six different sites of the porcine myocardium at the peri-infarct zone immediately after ligating the left descending coronary artery. An identical dose of AAV-Cytomegalovirus (CMV)LacZ or saline was injected into control animals. AAV genomes were detected in the liver in addition to the heart. RT-PCR, Western blotting, and ELISA analyses showed that VEGF and Ang1 were predominantly expressed in the myocardium in the infarct core and border of the infarct heart. Gated single-photon emission computed tomography analyses showed that the VEGF/Ang1 group had better cardiac function and myocardial perfusion at 8 wk than at 2 wk after vector injection. Compared with the saline and LacZ controls, the VEGF/Ang1 group expressed higher phosphorylated Akt and Bcl-xL, less Caspase-3 and Bad, and had higher vascular density, more proliferating cardiomyocytes, and less apoptotic cells in the infarct and peri-infarct zones. Thus, cardiac-specific and hypoxia-induced coexpression of VEGF and Ang1 improves the perfusion and function of porcine MI heart through the induction of angiogenesis and cardiomyocyte proliferation, activation of prosurvival pathways, and reduction of cell apoptosis.

authors

Tao Z,Chen B,Tan X,Zhao Y,Wang L,Zhu T,Cao K,Yang Z,Kan YW,Su H

doi

10.1073/pnas.1018925108

subject

Has Abstract

pub_date

2011-02-01 00:00:00

pages

2064-9

issue

5

eissn

0027-8424

issn

1091-6490

pii

1018925108

journal_volume

108

pub_type

杂志文章
  • Antibodies to the binding site of the receptor for luteinizing hormone-releasing hormone (LHRH): generation with a synthetic decapeptide encoded by an RNA complementary to LHRH mRNA.

    abstract::A molecular recognition code has been hypothesized to exist in which ligands and their binding sites are encoded on complementary segments of genomic DNA. We have tested this hypothesis by generating a rabbit antibody to a synthetic decapeptide (complementary peptide) encoded by an RNA complementary to the mRNA for lu...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.24.9714

    authors: Mulchahey JJ,Neill JD,Dion LD,Bost KL,Blalock JE

    更新日期:1986-12-01 00:00:00

  • Linkage of recognition and replication functions by assembling combinatorial antibody Fab libraries along phage surfaces.

    abstract::We describe a method based on a phagemid vector with helper phage rescue for the construction and rapid analysis of combinatorial antibody Fab libraries. This approach should allow the generation and selection of many monoclonal antibodies. Antibody genes are expressed in concert with phage morphogenesis, thereby allo...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.10.4363

    authors: Kang AS,Barbas CF,Janda KD,Benkovic SJ,Lerner RA

    更新日期:1991-05-15 00:00:00

  • Cloning of the cDNA encoding a myosin heavy chain B isoform of Xenopus nonmuscle myosin with an insert in the head region.

    abstract::The complete amino acid sequence of Xenopus laevis nonmuscle myosin heavy chain B (MHC-B) has been deduced from overlapping cDNA clones isolated from an XTC cell library. RNA blots of various developmental stages, adult tissues, and XTC cells detect a single transcript of 7.5 kb which is expressed at similar levels th...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.7.2856

    authors: Bhatia-Dey N,Adelstein RS,Dawid IB

    更新日期:1993-04-01 00:00:00

  • Infectious viral DNA of murine leukemia virus.

    abstract::A fraction of the unintegrated viral DNA that appears early after infection of mouse cells by Moloney leukemia virus is infectious. The infectivity could be deomonstrated by an XC plaque assay of the cells exposed to DNA co-precipitated with calcium phosphate. The number of plaques deriving from closed-circular, super...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.12.4910

    authors: Smotkin D,Gianni AM,Rozenblatt S,Weinberg RA

    更新日期:1975-12-01 00:00:00

  • Heterogeneities in the transmission of infectious agents: implications for the design of control programs.

    abstract::From an analysis of the distributions of measures of transmission rates among hosts, we identify an empirical relationship suggesting that, typically, 20% of the host population contributes at least 80% of the net transmission potential, as measured by the basic reproduction number, R0. This is an example of a statist...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.1.338

    authors: Woolhouse ME,Dye C,Etard JF,Smith T,Charlwood JD,Garnett GP,Hagan P,Hii JL,Ndhlovu PD,Quinnell RJ,Watts CH,Chandiwana SK,Anderson RM

    更新日期:1997-01-07 00:00:00

  • Specific cleavage analysis of mammalian mitochondrial DNA.

    abstract::Mitochondrial DNA from several mammalian species has been digested with a site-specific restriction endonuclease (HaeIII) from Haemophilus aegyptius. A quantitative analysis of the resulting specific fragments indicates that the mtDNA of any individual mammal is predominantly a single molecular clone. Gel analysis of ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.11.4496

    authors: Potter SS,Newbold JE,Hutchison CA 3rd,Edgell MH

    更新日期:1975-11-01 00:00:00

  • Site-specific characterization of threonine, serine, and tyrosine glycosylations of amyloid precursor protein/amyloid beta-peptides in human cerebrospinal fluid.

    abstract::The proteolytic processing of human amyloid precursor protein (APP) into shorter aggregating amyloid β (Aβ)-peptides, e.g., Aβ1-42, is considered a critical step in the pathogenesis of Alzheimer's disease (AD). Although APP is a well-known membrane glycoprotein carrying both N- and O-glycans, nothing is known about th...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1102664108

    authors: Halim A,Brinkmalm G,Rüetschi U,Westman-Brinkmalm A,Portelius E,Zetterberg H,Blennow K,Larson G,Nilsson J

    更新日期:2011-07-19 00:00:00

  • Translation of mRNAs with degenerate initiation triplet AUU displays high initiation factor 2 dependence and is subject to initiation factor 3 repression.

    abstract::The influence of the rare initiation triplet AUU on mRNA translation was investigated by comparing the activity of two pairs of model mRNAs that differ in the length of Shine-Dalgarno and spacer sequences. Irrespective of the initiation triplet (AUG or AUU), all mRNAs had similar template activity in vitro, but transl...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.9.4161

    authors: La Teana A,Pon CL,Gualerzi CO

    更新日期:1993-05-01 00:00:00

  • Expression in Escherichia coli of chemically synthesized genes for human insulin.

    abstract::Synthetic genes for human insulin A and B chains were cloned separately in plasmid pBR322. The cloned synthetic genes were then fused to an Escherichia coli beta-galactosidase gene to provide efficient transcription and translation and a stable precursor protein. The insulin peptides were cleaved from beta-galactosida...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.76.1.106

    authors: Goeddel DV,Kleid DG,Bolivar F,Heyneker HL,Yansura DG,Crea R,Hirose T,Kraszewski A,Itakura K,Riggs AD

    更新日期:1979-01-01 00:00:00

  • Cloning and characterization of a cell surface receptor for xenotropic and polytropic murine leukemia viruses.

    abstract::Xenotropic and polytropic murine leukemia viruses (X-MLVs and P-MLVs) cross-interfere to various extents in non-mouse species and in wild Asian mice, suggesting that they might use a common receptor for infection. Consistent with this hypothesis, the susceptibility of some wild mice to X-MLVs has been mapped to the P-...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.3.927

    authors: Tailor CS,Nouri A,Lee CG,Kozak C,Kabat D

    更新日期:1999-02-02 00:00:00

  • Substitution of a single amino acid (aspartic acid for histidine) converts the functional activity of human complement C4B to C4A.

    abstract::The C4B isotype of the fourth component of human complement (C4) displays 3- to 4-fold greater hemolytic activity than does its other isotype C4A. This correlates with differences in their covalent binding efficiencies to erythrocytes coated with antibody and complement C1. C4A binds to a greater extent when C1 is on ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.17.6868

    authors: Carroll MC,Fathallah DM,Bergamaschini L,Alicot EM,Isenman DE

    更新日期:1990-09-01 00:00:00

  • In silico discovery of small-molecule Ras inhibitors that display antitumor activity by blocking the Ras-effector interaction.

    abstract::Mutational activation of the Ras oncogene products (H-Ras, K-Ras, and N-Ras) is frequently observed in human cancers, making them promising anticancer drug targets. Nonetheless, no effective strategy has been available for the development of Ras inhibitors, partly owing to the absence of well-defined surface pockets s...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1217730110

    authors: Shima F,Yoshikawa Y,Ye M,Araki M,Matsumoto S,Liao J,Hu L,Sugimoto T,Ijiri Y,Takeda A,Nishiyama Y,Sato C,Muraoka S,Tamura A,Osoda T,Tsuda K,Miyakawa T,Fukunishi H,Shimada J,Kumasaka T,Yamamoto M,Kataoka T

    更新日期:2013-05-14 00:00:00

  • Differences in spontaneous mutation frequencies as a function of environmental stress in soil fungi at "Evolution Canyon," Israel.

    abstract::When various wild strains of Penicillium lanosum and Aspergillus niger were placed in the same mild laboratory environment, their frequencies of new spontaneous mutations were clearly related to whether they had been isolated from a region of high or low microclimatic stress. In the mild environment, the total frequen...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0801995105

    authors: Lamb BC,Mandaokar S,Bahsoun B,Grishkan I,Nevo E

    更新日期:2008-04-15 00:00:00

  • Monte Carlo study of the GTP cap in a five-start helix model of a microtubule.

    abstract::Earlier Monte Carlo studies on a single-helix model of the GTP cap at the end of a microtubule are extended here to a more realistic five-start helix model of the microtubule end. As in the earlier work, phase changes occur at the microtubule end: the end is either capped with GTP and growing slowly or uncapped and sh...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.4.1131

    authors: Chen YD,Hill TL

    更新日期:1985-02-01 00:00:00

  • SK channels mediate NADPH oxidase-independent reactive oxygen species production and apoptosis in granulocytes.

    abstract::Neutrophils are immune cells that bind to, engulf, and destroy bacterial and fungal pathogens in infected tissue, and their clearance by apoptosis is essential for the resolution of inflammation. Killing involves both oxidative and nonoxidative processes, the oxidative pathway requiring electrogenic production of supe...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0607914103

    authors: Fay AJ,Qian X,Jan YN,Jan LY

    更新日期:2006-11-14 00:00:00

  • Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita.

    abstract::Dyskeratosis congenita is a rare inherited disorder characterized by abnormal skin manifestations. Morbidity and mortality from this disease is usually due to bone marrow failure, but idiopathic pulmonary fibrosis and an increased cancer predisposition also occur. Families with autosomal dominant dyskeratosis congenit...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0508124102

    authors: Armanios M,Chen JL,Chang YP,Brodsky RA,Hawkins A,Griffin CA,Eshleman JR,Cohen AR,Chakravarti A,Hamosh A,Greider CW

    更新日期:2005-11-01 00:00:00

  • The kinesin-1 motor protein is regulated by a direct interaction of its head and tail.

    abstract::Kinesin-1 is a molecular motor protein that transports cargo along microtubules. Inside cells, the vast majority of kinesin-1 is regulated to conserve ATP and to ensure its proper intracellular distribution and coordination with other molecular motors. Regulated kinesin-1 folds in half at a hinge in its coiled-coil st...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0803575105

    authors: Dietrich KA,Sindelar CV,Brewer PD,Downing KH,Cremo CR,Rice SE

    更新日期:2008-07-01 00:00:00

  • Copper economy in Chlamydomonas: prioritized allocation and reallocation of copper to respiration vs. photosynthesis.

    abstract::Inorganic elements, although required only in trace amounts, permit life and primary productivity because of their functions in catalysis. Every organism has a minimal requirement of each metal based on the intracellular abundance of proteins that use inorganic cofactors, but elemental sparing mechanisms can reduce th...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1422492112

    authors: Kropat J,Gallaher SD,Urzica EI,Nakamoto SS,Strenkert D,Tottey S,Mason AZ,Merchant SS

    更新日期:2015-03-03 00:00:00

  • Bathorhodopsin intermediates from 11-cis-rhodopsin and 9-cis-rhodopsin.

    abstract::Bathorhodopsin-rhodopsin difference spectra of native 11-cis-rhodopsin and regenerated 9-cis-rhodopsin were measured at room temperature with a double-beam laser spectrophotometer after excitation at 532 nm. A detailed analysis of data obtained at 85 psec after excitation suggests that the bathorhodopsins generated fr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.80.7.1887

    authors: Spalink JD,Reynolds AH,Rentzepis PM,Sperling W,Applebury ML

    更新日期:1983-04-01 00:00:00

  • A scaling law derived from optimal dendritic wiring.

    abstract::The wide diversity of dendritic trees is one of the most striking features of neural circuits. Here we develop a general quantitative theory relating the total length of dendritic wiring to the number of branch points and synapses. We show that optimal wiring predicts a 2/3 power law between these measures. We demonst...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1200430109

    authors: Cuntz H,Mathy A,Häusser M

    更新日期:2012-07-03 00:00:00

  • Interaction of Galpha 12 and Galpha 13 with the cytoplasmic domain of cadherin provides a mechanism for beta -catenin release.

    abstract::The G12 subfamily of heterotrimeric G proteins, comprised of the alpha-subunits Galpha12 and Galpha13, has been implicated as a signaling component in cellular processes ranging from cytoskeletal changes to cell growth and oncogenesis. In an attempt to elucidate specific roles of this subfamily in cell regulation, we ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.021350998

    authors: Meigs TE,Fields TA,McKee DD,Casey PJ

    更新日期:2001-01-16 00:00:00

  • Interplay between Drosophila Bloom's syndrome helicase and Ku autoantigen during nonhomologous end joining repair of P element-induced DNA breaks.

    abstract::P transposable elements in Drosophila are mobilized via a cut-and-paste mechanism. The broken DNA ends generated during transposition can be repaired via the homology-directed synthesis-dependent strand annealing or by nonhomologous end joining (NHEJ). Genetic studies have demonstrated an interaction between the gene ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0403000101

    authors: Min B,Weinert BT,Rio DC

    更新日期:2004-06-15 00:00:00

  • Construction of Tn5 lac, a transposon that fuses lacZ expression to exogenous promoters, and its introduction into Myxococcus xanthus.

    abstract::A promoterless trp-lac fusion fragment was inserted near one end of the bacterial transposon Tn5 in the correct orientation to fuse lacZ gene expression to promoters outside Tn5. The resulting transposon, Tn5 lac, retains the kanamycin-resistance gene of Tn5 and transposes in Escherichia coli at 6% the frequency of Tn...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.18.5816

    authors: Kroos L,Kaiser D

    更新日期:1984-09-01 00:00:00

  • Structural changes and metal binding by proalbumins and other amino-terminal genetic variants of human serum albumin.

    abstract::Proalbumins are rare genetic variants of human serum albumin containing a basic propeptide that is not removed during post-transcriptional processing because of a mutation in the site of excision, an Arg-Arg sequence. We have identified the amino acid substitutions in three different types of proalbumins designated Ga...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.84.21.7403

    authors: Takahashi N,Takahashi Y,Putnam FW

    更新日期:1987-11-01 00:00:00

  • In vivo HIV-1 infection of CD45RA(+)CD4(+) T cells is established primarily by syncytium-inducing variants and correlates with the rate of CD4(+) T cell decline.

    abstract::Switch from non-syncytium-inducing (NSI) to syncytium-inducing (SI) HIV type 1 (HIV-1) is associated with accelerated CD4(+) T cell depletion, which might partially be explained by higher virulence of SI variants compared with NSI variants. Because NSI and SI variants use different coreceptors for entry of target cell...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.97.3.1269

    authors: Blaak H,van't Wout AB,Brouwer M,Hooibrink B,Hovenkamp E,Schuitemaker H

    更新日期:2000-02-01 00:00:00

  • Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors.

    abstract::The mammalian AML/CBFalpha runt domain (RD) transcription factors regulate hematopoiesis and osteoblast differentiation. Like their Drosophila counterparts, most mammalian RD proteins terminate in a common pentapeptide, VWRPY, which serves to recruit the corepressor Groucho (Gro). Using a yeast two-hybrid assay, in vi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.20.11590

    authors: Levanon D,Goldstein RE,Bernstein Y,Tang H,Goldenberg D,Stifani S,Paroush Z,Groner Y

    更新日期:1998-09-29 00:00:00

  • Network topology for the formation of solvated electrons in binary CaO-Al2O3 composition glasses.

    abstract::Glass formation in the CaO-Al2O3 system represents an important phenomenon because it does not contain typical network-forming cations. We have produced structural models of CaO-Al2O3 glasses using combined density functional theory-reverse Monte Carlo simulations and obtained structures that reproduce experiments (X-...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1300908110

    authors: Akola J,Kohara S,Ohara K,Fujiwara A,Watanabe Y,Masuno A,Usuki T,Kubo T,Nakahira A,Nitta K,Uruga T,Weber JK,Benmore CJ

    更新日期:2013-06-18 00:00:00

  • Two mammalian heat shock proteins, HSP90 and HSP100, are actin-binding proteins.

    abstract::Two high molecular weight heat shock proteins, HSP90 (Mr, 90,000) and HSP100 (Mr, 100,000), were separately purified from extracts of cultured cells of a mouse lymphoma cell line, L5178Y. Both of the HSPs exist in homodimeric form under physiological conditions. Their physicochemical properties are quite similar to ea...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.21.8054

    authors: Koyasu S,Nishida E,Kadowaki T,Matsuzaki F,Iida K,Harada F,Kasuga M,Sakai H,Yahara I

    更新日期:1986-11-01 00:00:00

  • Immunologic evidence that the gene for L-gulono-gamma-lactone oxidase is not expressed in animals subject to scurvy.

    abstract::L-Gulono-gamma-lactone oxidase (L-gulono-gamma-lactone:oxygen 2-oxidoreductase, EC 1.1.3.8) is the enzyme that catalyzes the terminal step of L-ascorbic acid biosynthesis in mammalian liver. The absence of the oxidase activity in primates and guinea pigs is the reason why these animals are subject to scurvy, which mus...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.73.6.2066

    authors: Nishikimi M,Udenfriend S

    更新日期:1976-06-01 00:00:00

  • Protein kinase C is present in human sperm: possible role in flagellar motility.

    abstract::We report the presence of protein kinase C (PKC) in ejaculated human sperm as revealed by enzymatic activity assay and indirect immunohistochemistry. PKC is localized in the equatorial segment and in the principal piece of the tail. Addition of phorbol 12-myristate 13-acetate resulted in increased flagellar motility t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.18.7305

    authors: Rotem R,Paz GF,Homonnai ZT,Kalina M,Naor Z

    更新日期:1990-09-01 00:00:00