Delayed angiogenesis in aging rats and therapeutic effect of adenoviral gene transfer of VEGF.

Abstract:

:We have studied an age-related impairment in angiogenesis and evaluated the effect of overexpressing VEGF in this situation. Polyvinyl alcohol sponges were implanted subcutaneously into aged (24-month), adult (12-month), and young (2-month) rats. Blood vessel ingrowth and proliferative activity in the sponges were assessed by histology with immunostaining for von Willebrand's factor and proliferating cell nuclear antigen (PCNA), respectively. The percentage of total sponge area filled with ingrowing fibrovascular tissue was minimal in aged rats, intermediate in adult rats and highest in young rats. A similar pattern was observed for the total blood vessel numbers in the sponges from old to young animals. The percentage of total sponge endothelial cells (ECs) showing proliferative activity (PCNA positive) was lowest in the aged animals, intermediate in the adult rats and highest in the young rats. To further explore the mechanism of impaired angiogenesis in aged animals, we investigated and found a reduced level of endogenous VEGF protein expression in 12-month-old rats compared to that in 2-month-old rats. VEGF121 gene transfer significantly enhanced blood vessel and fibrovascular tissue ingrowth in adult/aged rats. Adenoviral-VEGF gene transfer also significantly stimulated EC proliferation in aged and adult rats. However, identical treatment failed to further stimulate the already more robust angiogenesis in young animals. The different angiogenic response in adult vs. young rats was not due to differences in gene transfer efficiency, since similar levels of human VEGF121 protein was detected in adult and young rats. Our results indicate that the decreased angiogenic response with aging is associated with reduced EC proliferation and reduced endogenous VEGF production. Adenoviral-VEGF121 gene transfer is effective in augmenting angiogenesis, particularly in older animals.

journal_name

Int J Mol Med

authors

Wang H,Keiser JA,Olszewski B,Rosebury W,Robertson A,Kovesdi I,Gordon D

subject

Has Abstract

pub_date

2004-04-01 00:00:00

pages

581-7

issue

4

eissn

1107-3756

issn

1791-244X

journal_volume

13

pub_type

杂志文章
  • MicroRNA profiles following metformin treatment in a mouse model of non-alcoholic steatohepatitis.

    abstract::Non-alcoholic steatohepatitis (NASH) is one of the most common causes of chronic liver disease and is considered to be a causative factor of cryptogenic cirrhosis and hepatocellular carcinoma. microRNAs (miRNAs) are small non-coding RNAs that negatively regulate messenger RNA (mRNA). Recently, it was demonstrated that...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2015.2092

    authors: Katsura A,Morishita A,Iwama H,Tani J,Sakamoto T,Tatsuta M,Toyota Y,Fujita K,Kato K,Maeda E,Nomura T,Miyoshi H,Yoneyama H,Himoto T,Fujiwara S,Kobara H,Mori H,Niki T,Ono M,Hirashima M,Masaki T

    更新日期:2015-04-01 00:00:00

  • Coordinated increase of miRNA-155 and miRNA-196b expression correlates with the detection of the antigenomic strand of hepatitis C virus in peripheral blood mononuclear cells.

    abstract::A tight relationship has been revealed between cellular microRNAs (miRNAs) and the course of hepatitis C virus (HCV) replication in human hepatoma cells. Although the detection of the antigenomic HCV RNA strand in peripheral blood mononuclear cells (PBMCs) has provided evidence for viral replication in PBMCs, no repor...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2011.748

    authors: Grek M,Piekarska A,Bartkowiak J,Fendler W,Kuydowicz J,Wroblewski P,Paradowski M,Sidorkiewicz M

    更新日期:2011-11-01 00:00:00

  • Expression of multidrug resistance associated transporters (MDR1, MRP1, LRP and BCRP) in porcine oocyte.

    abstract::Transporters such as P-glycoprotein (MDR1), multidrug resistance protein 1 (MRP1), lung resistance-related protein (LRP) and breast cancer resistance protein (BCRP) are associated with multidrug resistance in various carcinoma cell lines. The expression of these molecules has been also characterized in human normal ti...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.7.4.397

    authors: Takebayashi Y,Nakayama K,Fujioka T,Kanzaki A,Mutho M,Uchida T,Miyazaki K,Ito M,Fukumoto M

    更新日期:2001-04-01 00:00:00

  • Sequential fluctuation pattern of serum des-gamma-carboxy prothrombin levels detected by high-sensitive electrochemiluminescence system as an early predictive marker for hepatocellular carcinoma in patients with cirrhosis.

    abstract::Serum concentration levels of des-gamma-carboxy prothrombin (DCP), alpha-fetoprotein (AFP) and Lens culinaris agglutinin-reactive fraction (AFP-L3) are useful tumor markers for the diagnosis of hepatocellular carcinoma (HCC). Recently, a novel immunoassay using the electrochemiluminescence (ECLIA) was developed to ena...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Shimizu A,Shiraki K,Ito T,Sugimoto K,Sakai T,Ohmori S,Murata K,Takase K,Tameda Y,Nakano T

    更新日期:2002-03-01 00:00:00

  • Effects of a Rho kinase inhibitor on the sequential expression of ICAM-1, HIF-1α, Bcl-2 and caspase-3 in the retina of rats with oxygen-induced retinopathy.

    abstract::The aim of the present study was to evaluate the effects of blocking the Rho kinase pathway on non-perfused regions and angiogenesis in the retina of rats using a rat model of oxygen-induced retinopathy (OIR) by observing the sequential expression of intercellular adhesion molecule-1 (ICAM-1), hypoxia-inducible factor...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2013.1410

    authors: Wang H,Chen X

    更新日期:2013-08-01 00:00:00

  • Therapeutic effect of ARBs on insulin resistance and liver injury in patients with NAFLD and chronic hepatitis C: a pilot study.

    abstract::Fatty liver is one of the local morphological manifestations of metabolic syndrome and is frequently associated with insulin resistance. Insulin resistance is also common in patients with chronic hepatitis C. Hyperinsulinemia is an independent risk factor for hypertension and cardiovascular mortality. The aim of this ...

    journal_title:International journal of molecular medicine

    pub_type: 临床试验,杂志文章

    doi:

    authors: Enjoji M,Kotoh K,Kato M,Higuchi N,Kohjima M,Nakashima M,Nakamuta M

    更新日期:2008-10-01 00:00:00

  • Induction of heme oxygenase‑1 expression protects articular chondrocytes against cilostazol‑induced cellular senescence.

    abstract::Chondrocyte senescence is associated with the aging and degeneration of cartilage, and eventually leads to joint destruction. The aim of this study was to elucidate the mechanisms responsible for the cytoprotective effects of heme oxygenase‑1 (HO‑1) on chondrocytes in cartilage. Chondrocyte senescence was induced usin...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2014.1918

    authors: Kim KM,Park SE,Lee MS,Kim K,Park YC

    更新日期:2014-11-01 00:00:00

  • IQGAP1 modulates the proliferation and migration of vascular smooth muscle cells in response to estrogen.

    abstract::Vascular smooth muscle cell (VSMC) proliferation and migration has been proven to be a critical event in the development of varicosity. Variations in estrogen levels, a pathological event related to age and pregnancy, play a role in the pathogenesis of varicosity. Previous studies have reported a different response of...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2015.2134

    authors: Huang X,Jin Y,Zhou D,Xu G,Huang J,Shen L

    更新日期:2015-05-01 00:00:00

  • Quercetin inhibits the growth of human gastric cancer stem cells by inducing mitochondrial-dependent apoptosis through the inhibition of PI3K/Akt signaling.

    abstract::Cancer stem cells (CSCs) have recently been linked to new treatment strategies for gastric cancer due to the critical role which they play as the 'heartbeat' of cancer. In the present study, we explored the effects of quercetin, an anti-inflammatory and antiviral compound, on gastric CSCs (GCSCs). We noted that quercet...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2016.2625

    authors: Shen X,Si Y,Wang Z,Wang J,Guo Y,Zhang X

    更新日期:2016-08-01 00:00:00

  • Investigating the regulatory role of ORMDL3 in airway barrier dysfunction using in vivo and in vitro models.

    abstract::The airway epithelium (AE) is the main protective barrier between the host and external environmental factors causing asthma. Allergens or pathogens induce AE dysfunction, including epithelial permeability alteration, trans‑epithelial electrical resistance (TEER) reduction, upregulation of inflammatory mediators and d...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2019.4233

    authors: Yang R,Tan M,Xu J,Zhao X

    更新日期:2019-08-01 00:00:00

  • Epithelial-mesenchymal transition is necessary for acquired resistance to cisplatin and increases the metastatic potential of nasopharyngeal carcinoma cells.

    abstract::Radiotherapy and adjuvant cisplatin (DDP) chemotherapy are standard approaches used in the treatment of nasopharyngeal carcinoma (NPC). However, resistance to chemotherapy has recently become more common, resulting in the failure of this combination therapy for NPC. The aim of the present study was to assess the cellu...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2013.1538

    authors: Zhang P,Liu H,Xia F,Zhang QW,Zhang YY,Zhao Q,Chao ZH,Jiang ZW,Jiang CC

    更新日期:2014-01-01 00:00:00

  • Acute in vivo effects of leptin and leptin fragments on corticosteroid hormone secretion and entero-insular axis in the rat.

    abstract::Leptin is a 147-amino acid adipose tissue-secreted hormone, which acts via several subtypes of receptors, the main and better known variants of which are named Ob-Ra and Ob-Rb. Structure-activity relationship studies pointed out the importance of the N-terminal and C-terminal amino-acid sequences 22-115 and 116-166, r...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Malendowicz LK,Gorska T,Tortorella C,Nowak M,Majchrzak M,Spinazzi R,Nussdorfer GG,Nowak KW

    更新日期:2004-06-01 00:00:00

  • Adrenomedullin is expressed in cord blood hematopoietic cells and stimulates their clonal growth.

    abstract::Adrenomedullin (AM) is a hypotensive peptide, which originates from the proteolytic cleavage of pro(p)AM and acts via AM22-52-sensitive receptors. Reverse transcription polymerase chain reaction allowed the detection of the specific mRNAs of pAM in the mononuclear hematopoietic cells of the cord blood and immunocytoch...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Del Pup L,Belloni AS,Carraro G,De Angeli S,Parnigotto PP,Nussdorfer GG

    更新日期:2003-02-01 00:00:00

  • Mesenchymal stem cells contribute to the renal repair of acute tubular epithelial injury.

    abstract::Acute renal failure (ARF) is a common disease with high morbidity and mortality. Recovery from ARF is dependent on the replacement of necrotic tubular cells with functional tubular epithelium. Recent advancement in developmental biology led to the discovery of immature mesenchymal stem cells (MSCs) in bone marrow and ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Herrera MB,Bussolati B,Bruno S,Fonsato V,Romanazzi GM,Camussi G

    更新日期:2004-12-01 00:00:00

  • Overexpression of miR-200a protects cardiomyocytes against hypoxia-induced apoptosis by modulating the kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2 signaling axis.

    abstract::The kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling axis plays an important role in regulating oxidative stress in ischemic cardiomyocytes. Targeting Keap1 in order to promote Nrf2 activation is considered a potential method for protecting cardiomyocytes against...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2016.2719

    authors: Sun X,Zuo H,Liu C,Yang Y

    更新日期:2016-10-01 00:00:00

  • Diverse inhibition of plasminogen activator inhibitor type 1 by theaflavins of black tea.

    abstract::Fruits, vegetables, spices and a variety of teas are suggested for the prevention of many diseases. They encompass active, non-nutritional ingredients called nutraceuticals which are defined as food products that provide health benefits. Many nutraceuticals have been tested to identify inhibitors of plasminogen activa...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2011.615

    authors: Jankun J,Skotnicka M,Łysiak-Szydłowska W,Al-Senaidy A,Skrzypczak-Jankun E

    更新日期:2011-04-01 00:00:00

  • Secretogranin III may be an indicator of paraquat-induced astrocyte activation and affects the recruitment of BDNF during this process.

    abstract::Astrocyte activation has been described as a multi‑stage defensive response, which is characterized by the morphological alteration of astrocytes and the overexpression of intermediate filament proteins. However, the functional mechanism of the secretion system in activated astroglia remains unclear. It has previously...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2018.3909

    authors: Zhan X,Li F,Chu Q,Pang H

    更新日期:2018-12-01 00:00:00

  • N-3 fatty acid-rich diet prevents early response of interleukin-6 elevation in trinitrobenzene sulfonic acid-induced enteritis.

    abstract::Dietary fat is an important factor involved in the pathogenesis of inflammatory bowel disease (IBD). It remains unclear how n-3 and n-6 fatty acids modulate intestinal inflammation. In this study, we investigated the effects of n-3 and n-6 fatty acid-rich diets on trinitrobenzene sulfonic acid (TNBS)-induced enteritis...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Andoh A,Tsujikawa T,Ishizuka I,Araki Y,Sasaki M,Koyama S,Fujiyama Y

    更新日期:2003-11-01 00:00:00

  • Ectromelia virus upregulates the expression of heat shock protein 70 to promote viral replication.

    abstract::The ectromelia virus (ECTV) is a mouse specific Orthopoxvirus that causes lethal infection in some mouse strains. ECTV infection of these mouse strains has been used as a valuable model for understanding the interplay between Orthopoxvirus species and their hosts, including variola virus in humans. Although poxviruses...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2018.3655

    authors: Cheng W,Jia H,Wang X,He X,Jin Q,Cao J,Jing Z

    更新日期:2018-08-01 00:00:00

  • ACF7 regulates colonic permeability.

    abstract::Colonic paracellular permeability is regulated by various factors, including dynamics of the cytoskeleton. Recently, ACF7 has been found to play a critical role in cytoskeletal dynamics as an essential integrator. To elucidate the physiological importance of ACF7 and paracellular permeability, we conditionally knocked...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2013.1284

    authors: Liang Y,Shi C,Yang J,Chen H,Xia Y,Zhang P,Wang F,Han H,Qin H

    更新日期:2013-04-01 00:00:00

  • Regulation of calmodulin-stimulated cyclic nucleotide phosphodiesterase (PDE1): review.

    abstract::The response of living cells to change in cell environment depends on the action of second messenger molecules. The two second messenger molecules cAMP and Ca2+ regulate a large number of eukaryotic cellular events. Calmodulin-stimulated cyclic nucleotide phosphodiesterase (PDE1) is one of the key enzymes involved in ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章,评审

    doi:

    authors: Sharma RK,Das SB,Lakshmikuttyamma A,Selvakumar P,Shrivastav A

    更新日期:2006-07-01 00:00:00

  • Multi‑layered prevention and treatment of chronic inflammation, organ fibrosis and cancer associated with canonical WNT/β‑catenin signaling activation (Review).

    abstract::β‑catenin/CTNNB1 is an intracellular scaffold protein that interacts with adhesion molecules (E‑cadherin/CDH1, N‑cadherin/CDH2, VE‑cadherin/CDH5 and α‑catenins), transmembrane‑type mucins (MUC1/CD227 and MUC16/CA125), signaling regulators (APC, AXIN1, AXIN2 and NHERF1/EBP50) and epigenetic or transcriptional regulator...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章,评审

    doi:10.3892/ijmm.2018.3689

    authors: Katoh M

    更新日期:2018-08-01 00:00:00

  • EGFR monoclonal antibody panitumumab inhibits chronic proliferative cholangitis by downregulating EGFR.

    abstract::In hepatolithiasis, chronic proliferative cholangitis (CPC), an active and longstanding inflammation of stone‑containing bile ducts with enhanced mucin‑producing activity, not only affects the progression of the disease, it can also induce biliary carcinogenesis. The present study aimed to examine the effect of the ep...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2019.4190

    authors: Liu SH,Chen XF,Xie ZB,Zhou J

    更新日期:2019-07-01 00:00:00

  • Vaccination with embryonic stem cells generates effective antitumor immunity against ovarian cancer.

    abstract::To date, only a few studies have suggested that human embryonic stem cells (hESCs) might effectively immunize against colon and lung cancer. The purpose of this study was to investigate the therapeutic potential of hESCs as a vaccine to induce widespread antitumor effects in differe...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2012.1195

    authors: Zhang Z,Chen X,Chang X,Ye X,Li Y,Cui H

    更新日期:2013-01-01 00:00:00

  • Role of bone morphogenetic protein 2 in the crosstalk between endothelial progenitor cells and mesenchymal stem cells.

    abstract::In recent studies, we and others have demonstrated that bone morphogenetic protein-2 (BMP-2) promotes vascularization, inhibits hypoxic cell death of cancer cells and may be involved in tumor angiogenesis. The activation of circulating endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) represents a ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.18.4.735

    authors: Raida M,Heymann AC,Günther C,Niederwieser D

    更新日期:2006-10-01 00:00:00

  • Cytokine-induced neutrophil accumulation in the pathogenesis of acute reflux esophagitis in rats.

    abstract::Although recent reports indicate an increasing incidence of patients with reflux esophagitis, its pathomechanism remains unclear. Cytokines and neutrophils, the latter of which produce reactive oxygen species (ROS), have been implicated in the formation of gastrointestinal diseases. This study investigated the roles o...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Yamaguchi T,Yoshida N,Tomatsuri N,Takayama R,Katada K,Takagi T,Ichikawa H,Naito Y,Okanoue T,Yoshikawa T

    更新日期:2005-07-01 00:00:00

  • A highly efficient method for isolating urinary exosomes.

    abstract::In the present study, a highly efficient method, referred to as optimized ultrafiltration (OUF), was developed. This method is effective for exosome purification and also facilitates clinical work involving substantial urinary exosome isolation. In the OUF method, 0.22‑µm filters along with a dialysis membrane with a ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2018.3944

    authors: He L,Zhu D,Wang J,Wu X

    更新日期:2019-01-01 00:00:00

  • The metabolic syndrome of omega3-depleted rats. III. Brain phospholipids.

    abstract::Rats exposed from 7 weeks after birth and for the ensuing 3 to 7 months to a diet depleted in long-chain polyunsaturated omega3 fatty acids were recently proposed as a new animal model for the metabolic syndrome. The present study aimed mainly at investigating whether, in this new model, the perturbation of the fatty ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Portois L,Hacquebard M,Malaisse WJ,Carpentier YA

    更新日期:2009-08-01 00:00:00

  • Identification and characterization of epitopes from influenza A virus hemagglutinin that induce broadly cross-reactive antibodies.

    abstract::Influenza is the most common infectious disease and is caused by influenza A virus (IAV) infection. Hemagglutinin (HA) is an important viral protein of influenza A and is a major component of current IAV vaccines. The side effects associated with IAV vaccination are well studied; however, the HA‑induced immunopatholog...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2017.3344

    authors: Li Y,Hu H,Qi Z,Sun J,Li Y,Feng Q,Guo C,Wang H,Zhao P,Liu Y,Zhao X,Wang G,Zhang H,Liu L,Hu J

    更新日期:2018-03-01 00:00:00

  • Regulation of human prostate-specific antigen gene expression in transgenic mice: evidence for an enhancer between the PSA and human glandular kallikrein-1 genes.

    abstract::The human prostate-specific antigen (PSA) and glandular kallikrein-1 (hGK-1, also known as hK2) genes are tandemly located on chromosome 19, separated by a 12-kb intergenic region. The coordinate regulation of these two genes suggests the presence of common regulatory elements responsible for tissue specificity and/or...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2.4.487

    authors: Wei C,Callahan BP,Turner MJ,Willis RA,Lord EM,Barth RK,Frelinger JG

    更新日期:1998-10-01 00:00:00