Skip to main content
SpringerLink
Log in

Factors involved in capillary growth in the heart

  • Part I: Extracellular Matrix and Cardiocyte Interaction
  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Growth of capillaries in the heart occurs under physiological circumstances during endurance exercise training, exposure to high altitude and/or cold, and changes in cardiac metabolism or heart rate elicited by modification of thyroid hormone levels. Capillary growth in all these conditions can be linked with increased coronary blood flow, decreased heart rate, or both. This paper brings evidence that, although increased blood flow due to long-term administration of coronary vasodilators results in capillary growth, a long-term decrease in heart rate induced by electrical bradycardial pacing in rabbits and pigs, or by chronic administration of a bradycardic drug, alinidine, in rats, stimulates capillary growth with little or no change in coronary blood flow. Decreased heart rate results in increased capillary wall tension, increased end-diastolic volume and increased force of contraction, and thus stretch of the capillary wall. This could lead to release of various growth factors possibly stored in the capillary basement membrane. Correlation was found between capillary density (CD) and the levels of low molecular endothelial cell stimulating angiogenic factor (ESAF) both in rabbit and pig hearts with CD increased by pacing. There was no relation between expression of mRNA for basic fibroblast growth factor and CD in sham-operated and paced rabbit hearts. In contrast, mRNA for TGFß was increased in paced hearts, and the possible role of this factor in the regulation of capillary growth induced by bradycardia is discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Olivetti G, Anversa P, Melissari M, Loud AV: Morphometric study of early postnatal development of the thoracic aorta in the rat. Circ Res 47: 417–424, 1980

    PubMed  Google Scholar 

  2. Rakusan K: Cardiac growth, maturation and aging. In: R. Zak (ed). Growth of the Heart in Health, and Disease Raven Press, New York, 1984, pp 131–164

    Google Scholar 

  3. Hudlicka O, Brown MD, Egginton S: Angiogenesis in skeletal and cardiac muscle. Physiol Rev 72: 369–417, 1992

    PubMed  Google Scholar 

  4. Chilian WH, Wangler, RD, Peters KG, Tomanek RJ, Marcus ML: Thyroxine-induced left ventricular hypertrophy in the rat: anatomical and physiological evidence for angiogenesis. Circ Res 57: 591–598, 1985

    PubMed  Google Scholar 

  5. Tomanek RJ, Barlow PA, Connell PM, Chen Y, Torry RJ: Effects of hypothyroidism and hypertension on myocardial perfusion and vascularity in rabbits. Am J Physiol 265: H1638–1644, 1993

    PubMed  Google Scholar 

  6. Laughlin MH, McAllister RM: Exercise training-induced coronary vascular adaptation. J Appl Physiol 73: 2209–2225, 1992

    PubMed  Google Scholar 

  7. Folkman J, Klagsbrun M: A family of angiogenic peptides. Nature 329: 671, 1987

    PubMed  Google Scholar 

  8. Schaper W, Sharma HS, Quinkler W, Markert T, Wünsch M, Schaper J: Molecular biologic concepts of coronary anastomoses. J Am Coll Cardiol 15: 513–518, 1990

    PubMed  Google Scholar 

  9. Schaper W, Görge G, Winkler B, Schaper J: The colateral circulation of the heart. Prog Cardiovasc Dis 31: 57–77, 1988

    PubMed  Google Scholar 

  10. Hudlicka O: Capillary growth: role of mechanical factors. NIPS 3: 117–120, 1988

    Google Scholar 

  11. Tomanek RJ: Response of the coronary vasculature to myocardial hypertrophy. J Am Coll Cardiol 15: 528–533, 1990

    PubMed  Google Scholar 

  12. Tillmans H Steinhausen M, Leinberger H, Thederan H Kübler W: The effect of coronary vasodilators on the microcirculation of the ventricular myocardium. In: H. Tillmans, W. Kübler, H. Zebe (eds). Microcirculation of the Heart. Springer Verlag, Berlin, 1982, pp 305–312

    Google Scholar 

  13. Dawson JM, Hudlicka O: Can changes in microcirculation explain capillary growth in skeletal muscle? Int J Exp Path 74: 65–71, 1993

    Google Scholar 

  14. Tillmans TH, Ikeda S, Hansen H, Sarma JS, Fauvel JH, Bing RJ: Microcirculation in the ventricle of the dog and turtle Circ Res 34: 561–569, 1974

    PubMed  Google Scholar 

  15. Ando J, Nomura H, Kamiya A: The effect of fluid shear stress on the migration and proliferation of cultured endothelial cells. Microvasc Res 33: 62–70, 1987

    PubMed  Google Scholar 

  16. Ingber DE, Folkman J: Regulation of endothelial growth factor actionsolid state control by extracellular matrix. Progress in Clin Biol Res 249: 273–284, 1987

    Google Scholar 

  17. Sumpio BF, Banes AJ, Levin LG, Johnson G: Mechanical stress stimulates aortic endothelial cells to proliferate. J Vasc Surg 6: 252–256, 1987

    PubMed  Google Scholar 

  18. Malek AM, Gibbons GH, Dzau VJ, Izumo S: Fluid shear stress differentially modulates expression of genes encoding basic fibroblast growth factor and platelet-derived growth factor-B chain in vascular endothelium. J Clin Invest 92: 2013–2021, 1993

    PubMed  Google Scholar 

  19. Diamond SL, Sharefkin B, Dieffenbach C, Frasier-Scott K, McIntyre LV, Eskin, SG: Tissue plasminogen activator messenger RNA levels increase in cultured human endothelial cells exposed to laminar shear stress. J Cell Physiol 173: 364–371, 1990

    Google Scholar 

  20. Ausprunck DH: Tumor angiogenesis. In: J.C. Houck (ed). Handbook of Inflammation. Vol 1, Elsevier/North Holland, Amsterdam, 1979 pp 317–351

    Google Scholar 

  21. Odedra R, Weiss JB: Low molecular weight angiogenesis factors. Pharmac Ther 49: 111–124, 1991

    Google Scholar 

  22. Casscells W, Speier E, Sasse J, Klagsbrun M, Allen P, Lee M, Calvo B, Cjiba M, Haggroth L, Folkman J, Epstein SE: Isolation, characterization and localization of heparin-binding growth factors in the heart. J Clin Invest 85: 433–441, 1990

    PubMed  Google Scholar 

  23. Sharma HS, Zimmerman R: Growth factors and development of coronary collaterals. In: P. Cummins (ed). Growth Factors and the Cardiovascular System. KluwerAcademic Publishers Boston, 1993, pp 119–148

    Google Scholar 

  24. Ziada AMAR, Hudlicka O, Tyler KR, Wright AJA: The effect of longterm vasodilation on capillary growth and performance in rabbit heart and skeletal muscle. Cardiovasc Res 18: 724–732, 1984

    PubMed  Google Scholar 

  25. Wright AJA, Hudlicka O: Capillary growth and changes in heart performance induced by chronic bradycardial pacing in the rabbit. Circ Res 49: 469–478, 1981

    PubMed  Google Scholar 

  26. Brown MD, Davies MK, Hudlicka O, Townsend P: Long-term bradycardia in the conscious pig produced by electrical pacing: effects on myocardial capillary supply. J Physiol 475: 62P, 1994

  27. Tyler KR, Wright AJA: Lightweight portable stimulators for stimulation of skeletal muscles at different frequencies and for cardiac pacing. J Physiol 307: 8–9P, 1980

    Google Scholar 

  28. Brown MD, Hudlicka O: Cardiac performancein vivo and anatomical capillary supply in the rabbit after prolonged dobutamine infusion. Cardiovasc Res 25: 909–915, 1991

    PubMed  Google Scholar 

  29. Schrock GD, Krahmer RL, Ferguson JL: Coronary flow by left atrial and left ventricular microsphere injection in the rat. Am J Physiol 259: H635–638, 1990

    PubMed  Google Scholar 

  30. Alroy J, Goyal V, Skutelsky E: Lectin histochemistry of mammalian endothelium. Histochemistry 86: 603–607, 1987

    PubMed  Google Scholar 

  31. Cooper RG, Taylor CM, Choo JJ, Weiss JB: Elevated endothelial-cell-stimulating-angiogenic factor activity in rodent glycolytic skeletal muscles. Clin Sci 81: 267–270, 1991

    PubMed  Google Scholar 

  32. Weiss JB, Hill CR, Davis RJ, McLaughlin B: Activation of mammalian procollagenase and basement membrane degrading enzymes by low-molecular weight angiogenesis factors. Agents and Actions 15: 107–108, 1984

    Google Scholar 

  33. Chomcyznski P, Sacchi N: Single step method of RNA isolation by Guanidinium thiocyanate-Phenol-Chloroform extraction. Anal Biochem 162: 156–159, 1987

    PubMed  Google Scholar 

  34. Shimasaki S, Emoto N, Koba A, Mercado M, Shibata F, Cooksey K, Baird A, Ling N: Complementary DNA cloning and sequencing of rat ovarian basic fibroblast growth factor and tissue distribution study of its mRNA. Biochem Biophys Res, Commun 157: 256–263, 1988

    Google Scholar 

  35. Quian SW, Kondaiah P, Roberts AB, Sporn MB: cDNA cloning by PCR of rat transforming growth factor beta 1. Nucl Acids Res 18: 3059–3063, 1990

    PubMed  Google Scholar 

  36. Ziada AMAR, Hudlicka O, Tyler KR: The effect of long-term administration of α1-blocker prazosin on capillary density in cardiac and skeletal muscle. Pflügers Arch 415: 355–360, 1989

    Google Scholar 

  37. Brown MD, Cleasby MJ, Hudlicka O: Capillary supply of hypertrophied rat hearts after chronic treatment with the bradycardic agent alinidine. J Physiol 427: 40P, 1990

  38. Hudlicka O, Wright AJA, Hoppeler H, Uhlmann E: The effect of chronic bradycardial pacing on the oxidative capacity in rabbit hearts. Resp Physiol 72: 1–12, 1988

    Google Scholar 

  39. Hudlicka O West D, Kumar S, El Khelly F, Wright AJA: Can growth of capillaries in the heart and skeletal muscle be explained by the presence of an angiogenic factor? Br J Exp Path 70: 237–246, 1989

    Google Scholar 

  40. Nellis SH, Liedtke AJ: Pressures and dimensions in the terminal vascular bed of the myocardium determined, by a new free motion technique. In: H. Tillmans W. Kübler, H. Zebe (eds) Microcirculation of the Heart. Springer Verlag, Berlin, 1982, pp 61–74

    Google Scholar 

  41. Hudlicka O, Brown MD: Physical forces and angiogenesis. In: G.M. Rubanyi (ed). Mechanoreception by the Vascular Wall Futura Publishing Co, Mount Kisco, NY, 1993, pp 197–241

    Google Scholar 

  42. Acevedo AD, Bowser SS, Gerritsen ME, Bizios R: Morphological and proliferative responses of endothelial cells to hydrostatic pressure—role of fibroblast growth factor. J Cell Physiol 157: 603–614, 1993

    PubMed  Google Scholar 

  43. Parker TG, Schneider MD: Growth factors, proto-oncogenes and plasticity of the cardiac phenotype. Ann Rev Physiol 53: 179–200, 1991

    Google Scholar 

  44. Schoefl GI, Majno G: Regeration of blood vessels in wound healing. In: Advances in Biology of Skin, Vol V, Pergamon, Oxford, UK, 1964, pp 73–193

    Google Scholar 

  45. Tornling G: Capillary neoformation in the heart of dipyridamole treated rats. Acta Pathol Microbiol Scand, sec A 90: 269–271, 1982

    Google Scholar 

  46. Poole DC, Batra S, Mathieu-Costello O, Rakusan K: Capillary geometrical changes with fiber shortening in rat myocardium. Circ Res 70: 697–706, 1992

    PubMed  Google Scholar 

  47. Mall G, Mattfeldt T, Reiger P Volk B, Frolov VA: Morphometric analysis of the rabbit myocardium after chronic ethanol feeding—early capillary changes. Basic Res Cardiol 77: 57–67, 1982

    PubMed  Google Scholar 

  48. Meininger CJ, Schelling ME, Granger HJ: Adenosine and hypoxia stimulate proliferation and migration of endothelial cells. Am J Physiol 255: H554-H562, 1988

    PubMed  Google Scholar 

  49. Jakob W, Zipper J, Savolvy SB, Siems W-E, Jentzsch KD: Is dipyridamole an aniogenic agent? Exp Pathol 22: 217–224, 1982

    PubMed  Google Scholar 

  50. Brown MD, Egginton S, Hudlicka O: Changes in capillary endothelial cell glycocalyx in rat skeletal muscles during chronic electrical stimulation. Int J Microciric Clin Exp 11: 447, 1992

    Google Scholar 

  51. Berthiaume F, Frangos JA: Fluid flow causes membrane perturbation in cultured human umbilical vein endothelial cells (HUVECS). FASEB J 4: A835, 1990

    Google Scholar 

  52. Hume WR: Proline and thymidine uptake in rabbit ear artery segmentsin vitro increased by chronic tangential load. Hypertension 2: 738–743, 1980

    PubMed  Google Scholar 

  53. Folkman J, Greenspan HP: Influence of geometry on control of cell growth. Biochem Biophys Acta 417: 211–231, 1975

    PubMed  Google Scholar 

  54. Folkman J, Klagsbrun M, Sasse J, Wadzinski M, Ingber DE, Vlodavsky I: A heparin-binding angiogenic protein—based fibroblast growth factor—is stored within basement membrane. Am J Pathol 130: 393–400, 1988

    PubMed  Google Scholar 

  55. Ingber DE, Folkman J: Regulation of endothelial growth factor action —solid state control by extracellular matrix. Progr Clin Biol Res 249: 273–284, 1987

    Google Scholar 

  56. Lansman JB, Hallam TJ, Rink TJ: Single stretch-activated ion channels in vascular endothelial cells as mechanotransducers? Nature 235: 811–812, 1987

    Google Scholar 

  57. Naruse K, Sokabe M: Involvement of stretch activated ion channels in Ca2+ mobilization to mechanical stretch in endothelial cells. Am J Physiol 264: C1037–1044, 1993

    PubMed  Google Scholar 

  58. Vlodavsky LK, Johnson D, Gospodarowicz R: Appearance in confluent vascular endothelial cell monolayers of a specific cell surface protein (CSP-60) not detected in actively growing in multiple leyers. Proc Natl Acad Sci USA, 76: 2306–2310, 1979

    PubMed  Google Scholar 

  59. Sumpio BF, Banes AJ Link GW, Iba T.: Modulation of endothelial cell phenotype by cyclic stretch: inhibition of collagen production. J Surg Res 48: 415–429, 1990

    PubMed  Google Scholar 

  60. Woessner FJ Jr: Matrix metalloproteinases and their inhibitors in connective tissue, remodelling. FASEB J 5: 2145–2154, 1991

    PubMed  Google Scholar 

  61. Brown MD, Hudlicka O, Fakhoury R, Weiss JB: Low molecular cell angiogenesis stimulating factor (ESAF) and capillary growth in skeletal muscles. Int J Microcirc Clin Exp 10: 40l, 1991

    Google Scholar 

  62. Kardami E, Fandrich RR: Basic fibroblast growth factor in atria and ventricles of the vertebrate heart. J Cell Biol 109: 1865–1871, 1989

    PubMed  Google Scholar 

  63. Davidson JM, Zoia O, Liu JM: Modulation of transforming growth-factor-beta-1 stimulated elastin and collagen production and proliferation in porcine vascular smooth muscle cells and skin fibroblasts by basic fibroblast growth factor alpha and insulin-like growth factor-1. J Cell Physiol 155: 149–156, 1993

    PubMed  Google Scholar 

  64. Antonelli-Orlidge A, Saunders KB, Smith SR, D'Amore PA: An activated form of TGFbeta is produced by co-cultures of endothelial cells and pericytes. Proc Natl Acad Sci USA 86: 4544–4548, 1989

    PubMed  Google Scholar 

  65. Iruela-Arispe ML, Sage EH: Endothelial cells exhibiting angiogenesis in vitro proliferate in response to TGF beta 1. J Cell Biochem 52: 414–430, 1993

    PubMed  Google Scholar 

  66. Gajdusek CM, Luo Z, Mayberg MR: Basic fibroblast growth factor and transforming growth factor beta-1: synergistic mediators of angiogenesis in vitro. J Cell Physiol 157: 133–144, 1993

    PubMed  Google Scholar 

  67. Phillips GD, Whitehead RA, Stone AM, Ruebel MW, Goodkin ML, Knighton DR: Transforming growth factor beta (TGF-β) stimulation of angiogenesis: an electron microscopic study. J Submicrosc Cytol Pathol 25: 149–155, 1993

    PubMed  Google Scholar 

  68. Pepper MS, Vassalli LD, Orci J, Montesano, R: Biphasic effect of transforming factor bata-1 on in vitro angiogenesis. Exp Cell Res 204: 356–363, 1992

    Google Scholar 

  69. Arciniegas E, Sutton AB, Allen TD, Schor AN: Transforming growth factor beta 1 promotes the differentiation of endothelial cells into smooth muscle-like cells in vitro. J Cell Sci 103: 521–529, 1992

    PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Margaret D. Brown

    Present address: School of Sport and Exercise Sciences, University of Birmingham, B15 2TT, Birmingham

  2. Helene Walter

    Present address: Department of Clinical Chemistry, Wolfson Research Laboratory, Queen Elizabeth Hospital, B15 2TT, Birmingham, UK

Authors and Affiliations

  1. Department of Physiology, University of Birmingham Medical School, B15 2TT, Birmingham, UK

    Olga Hudlická, Margaret D. Brown & Helene Walter

  2. Wolfson Angiogenesis Unit, Hope Hospital, University of Manchester, M6, Salford, UK

    Jacqueline B. Weiss & Anita Bate

Authors
  1. Olga Hudlická
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Margaret D. Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Helene Walter
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jacqueline B. Weiss
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anita Bate
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hudlická, O., Brown, M.D., Walter, H. et al. Factors involved in capillary growth in the heart. Mol Cell Biochem 147, 57–68 (1995). https://doi.org/10.1007/BF00944784

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00944784

Key words

Search

Navigation