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Regular Article| Volume 67, ISSUE 2, P137-146, February 01, 1997

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Induction of Angiogenesis by Lidocaine and Basic Fibroblast Growth Factor: A Model forin VivoRetroviral-Mediated Gene Therapy

DOI:https://doi.org/10.1006/jsre.1996.4989
Induction of Angiogenesis by Lidocaine and Basic Fibroblast Growth Factor: A Model forin VivoRetroviral-Mediated Gene Therapy
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Next ArticleVascular Endothelial Growth Factor Is the Major Angiogenic Factor in Omentum: Mechanism of the Omentum-Mediated Angiogenesis
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      Abstract

      A strategy of direct,in vivoretroviral-mediated gene therapy targeting capillary endothelial cells must provide an environment of active angiogenesis. Both lidocaine and basic fibroblast growth factor (bFGF) promote angiogenesis, but the angiogenic response invoked by these substances in normal skeletal muscle has not been fully characterized. We sought to characterize these agents’ angiogenic effects in anterior tibialis muscles of male Sprague–Dawley rats. An injection of either 1% lidocaine with 1:100,000 epinephrine or alternate-day injections of bFGF (0.025 or 0.25 μg) with or without heparin were tested (n= 6 muscles/condition). Rats were sacrificed 4, 7, 10, or 12 days later and muscles were evaluated histologically to determine the number of proliferating cells using 5-bromo-2′-deoxycytidine (BrdC) and evaluated for capillary density usingGriffonia simplicifoliaI (GSI) lectin. At all time points, lidocaine produced at least 20-fold greater capillary density and cellular proliferation than PBS control (P< 0.0001). Injections of high-dosage bFGF produced more than fivefold greater capillary density than control injections at 7 and 10 days (P< 0.001), and more than twofold greater proliferation at 4, 7, and 12 days (P< 0.001). Capillary density returned to control levels 12 days following bFGF administration, whereas it remained well above control levels for 12 days after lidocaine administration. To confirm that lidocaine can be utilized in gene therapy strategies targeting vascular endothelium and skeletal muscle fibers, concentrated pLJ retrovirus containing cDNA for the heat-stable human placental alkaline phosphatase (hpAP) marker gene was infused into the rat hindlimb vasculature 4 days post-lidocaine administration. Rats receiving pLJhpAP retrovirus demonstrated significant hpAP transgene expression in endothelial cells and myocytes 21 days after the lidocaine injection (n= 6 muscles). In contrast, controls receiving pLJhpAP infusion without prior lidocaine administration failed to demonstrate any hpAP transgene expression. Lidocaine treatment evokes a substantially higher proliferative response than bFGF and, importantly, a durable angiogenic response in skeletal muscle. Thus, lidocaine is an ideal agent to induce angiogenesis in preparation for directin vivoretroviral-mediated gene therapy targeting vascular endothelium.
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      References

      REFERENCES

        • Harris J.
        • Sikora K.
        Human genetic therapy.
        Mol. Asp. Med. 1993; 14: 451
        • Nabel E.G.
        • Pompili V.J.
        • Plautz G.E.
        • Nabel G.J.
        Gene transfer and vascular disease.
        Cardiovasc. Res. 1994; 28: 445
        • Messina L.M.
        • Podrazik R.M.
        • Whitehill T.A.
        • Ekhterae D.
        • Brothers T.E.
        • Wilson J.M.
        • Burkel W.E.
        • Stanley J.C.
        Adhesion and incorporation oflac-Z.
        Proc. Natl. Acad. Sci. USA. 1992; 89: 12018
        • Messina L.M.
        • Welling T.H.
        • Sarkar R.
        • Shanley C.J.
        • Stanley J.C.
        Gene Therapy for Vascular Disease.
        Advances in Surgical Gene Therapy. World Medical Press, Cedar Knolls1994 (p. 27–60)
        • Yao S.N.
        • Wilson J.M.
        • Nabel E.G.
        • Kurachi S.
        • Hachiya H.L.
        • Kurachi K.
        Expression of human factor IX in rat capillary endothelial cells: Toward somatic gene therapy for hemophilia B.
        Proc. Natl. Acad. Sci. USA. 1991; 88: 8101
        • Guyton A.C.
        Overview of the circulation, and medical physics of pressure, flow, and resistance.
        in: Wonsiewicz M.J. Textbook of Medical Physiology. Saunders, Philadelphia1991: 150-158
        • Messina L.M.
        • Faulkner J.A.
        The skeletal muscle.
        in: Zelenock G.B. Clinical Ischemic Syndromes. Mosby, St. Louis1990: 457-481
        • Dolwick M.F.
        • Bush F.M.
        • Seibel H.R.
        Regeneration of masseter muscle following lidocaine-induced degeneration: A histochemical study.
        Acta Anat. 1977; 98: 325
        • Foster A.H.
        • Carlson B.M.
        Myotoxicity of local anesthetics and regeneration of the damaged muscle fibers.
        Anesth. Analg. 1980; 59: 727
        • Carlson B.M.
        • Rainin E.A.
        Rat extraocular muscle regeneration: Repair of local anesthetic-induced damage.
        Arch. Ophthalmol. 1985; 103: 1373
        • Carlson B.M.
        • Shepard B.
        • Komorowski T.E.
        A histological study of local anesthetic-induced muscle degeneration and regeneration in the monkey.
        J. Orthoped. Res. 1990; 8: 485
        • Shing Y.
        • Folkman J.
        • Haudenschild C.
        • Lund D.
        • Crum R.
        • Klagsbrun M.
        Angiogenesis is stimulated by a tumor-derived endothelial cell growth factor.
        J. Cell. Biochem. 1985; 29: 275
        • Montesano R.
        • Vassalli J-D.
        • Baird A.
        • Guillemin R.
        • Orci L.
        Basic fibroblast growth factor induces angiogenesisin vitro.
        Proc. Natl. Acad. Sci. USA. 1986; 83: 7297
        • Folkman J.
        • Klagsbrun M.
        Angiogenic factors.
        Science. 1987; 235: 442
        • Villaschi S.
        • Nicosia R.F.
        Angiogenic role of endogenous basic fibroblast growth factor released by rat aorta after injury.
        Am. J. Pathol. 1993; 143: 181
        • Baffour R.
        • Berman J.
        • Garb J.L.
        • Rhee S.W.
        • Kaufman J.
        • Friedmann P.
        Enhanced angiogenesis and growth of collaterals byin vivo.
        J. Vasc. Surg. 1992; 16: 181
        • Moscatelli D.
        High and low affinity binding sites for basic fibroblast growth factor on cultured cells: Absence of a role for low affinity binding in the stimulation of plasminogen activator production by bovine capillary endothelial cells.
        J. Cell Physiol. 1987; 131: 123
        • Vigny M.
        • Ollier-Hartmann M.P.
        • Lavigne M.
        • Fayein N.
        • Jeanny J.C.
        • Laurent M.
        • Courtois Y.
        Specific binding of basic fibroblast growth factor to basement membrane-like structures and to purified heparan sulfate proteoglycan of the EHS tumor.
        J. Cell Physiol. 1988; 137: 321
        • Saksela O.
        • Moscatelli D.
        • Sommer A.
        • Rifkin D.B.
        Endothelial cell-derived heparan sulfate binds basic fibroblast growth factor and protects it from proteolytic degradation.
        J. Cell Biol. 1988; 107: 743
        • Bashkin P.
        • Doctrow S.
        • Klagsbrun M.
        • Svahn C.M.
        • Folkman J.
        • Vlodavsky I.
        Basic fibroblast growth factor binds to subendothelial extracellular matrix and is released by heparitinase and heparin-like molecules.
        Biochemistry. 1989; 28: 1737
        • Yayon A.
        • Klagsbrun M.
        • Esko J.D.
        • Leder P.
        • Ornitz D.M.
        Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor.
        Cell. 1991; 64: 841
        • Rapraeger A.C.
        • Krufka A.
        • Olwin B.B.
        Requirement of heparan sulfate for bFGF-mediated fibroblast growth and myoblast differentiation.
        Science. 1991; 252: 1705
        • Bauters C.
        • Asahara T.
        • Zheng L.P.
        • Takeshita S.
        • Bunting S.
        • Ferrara N.
        • Symes J.F.
        • Isner J.M.
        Site-specific therapeutic angiogenesis after systemic administration of vascular endothelial growth factor.
        J. Vasc. Surg. 1995; 21: 314
        • Lindner V.
        • Olson N.E.
        • Clowes A.W.
        • Reidy M.A.
        Inhibition of smooth muscle cell proliferation in injured rat arteries. Interaction of heparin with basic fibroblast growth factor.
        J. Clin. Invest. 1992; 90: 2044
        • Hansen-Smith F.M.
        • Watson L.
        • Lu D.Y.
        • Goldstein I.
        Griffonia simplicifolia.
        Microvasc. Res. 1988; 36: 199
        • Muller D.W.
        • Gordon D.
        • San H.
        • Yang Z.
        • Pompili V.J.
        • Nabel G.J.
        • Nabel E.G.
        Catheter-mediated pulmonary vascular gene transfer and expression.
        Circ. Res. 1994; 75: 1039
        • Fields-Berry S.C.
        • Halliday A.L.
        • Cepko C.L.
        A recombinant retrovirus encoding alkaline phosphatase confirms clonal boundary assignment in lineage analysis of murine retinal cells.
        Proc. Natl. Acad. Sci. USA. 1992; 89: 693
        • Sunderkotter C.
        • Steinbrink K.
        • Goebeler M.
        • Bhardwaj R.
        • Sorg C.
        Macrophages and angiogenesis.
        J. Leukocyte Biol. 1994; 55: 410
        • Vlodavsky I.
        • Folkman J.
        • Sullivan R.
        • Friedman R.
        • Ishai-Michaeli R.
        • Sasse J.
        • Klagsbrun M.
        Endothelial cell-derived basic fibroblast growth factor: Synthesis and deposition into subendothelial extracellular matrix.
        Proc. Natl. Acad. Sci. USA. 1987; 84: 2292
        • Folkman J.
        • Klagsbrun M.
        • Sasse J.
        • Wadzinski M.
        • Ingber D.
        • Vlodavsky I.
        A heparin-binding angiogenic protein—basic fibroblast growth factor—is stored within basement membrane.
        Am. J. Pathol. 1988; 130: 393
        • Saksela O.
        • Rifkin D.B.
        Release of basic fibroblast growth factor-heparan sulfate complexes from endothelial cells by plasminogen activator-mediated proteolytic activity.
        J. Cell Biol. 1990; 110: 767
        • Sato Y.
        • Rifkin D.B.
        Autocrine activities of basic fibroblast growth factor: Regulation of endothelial cell movement, plasminogen activator synthesis, and DNA synthesis.
        J. Cell. Biol. 1988; 107: 1199
        • Veomett G.
        • Kuszynski C.
        • Kazakoff P.
        • Rizzino A.
        Cell density regulates the number of cell surface receptors for fibroblast growth factor.
        Biochem. Biophys. Res. Commun. 1989; 159: 694

      Article info

      Footnotes

      ☆D. K. AndersenS. E. RaperL. M. MessinaJ. S. Economou, Eds.

      Identification

      DOI: https://doi.org/10.1006/jsre.1996.4989

      Copyright

      © 1997 Academic Press. Published by Elsevier Inc. All rights reserved.

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