Skip to main content

Advertisement

SpringerLink
Log in

Focus on cardiac pericytes

  • Invited Review
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

The wall of myocardial terminal vessels, consisting of a continuous endothelial tube with an adventitial coat of pericytes in their extracellular matrix, constitutes a remarkably tight barrier to solute transport between the blood and the parenchyma. This constructional principle of precapillary arterioles, capillaries and postcapillary venules extends both up- and downstream into the arterial and venous limbs, where the original microvessel tube widens and becomes the innermost layer—the intima—of all the larger coronary vessels. In the myocardium’s smallest functional units and in the intima of the coronaries, the pericytes play key roles by virtue of both their central histological localization and their physiological functions. Recognition and integration of these properties has led to new pathogenetic models for diverse heart diseases and suggests that current therapeutic concepts need to be revised.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

AP:

Alkaline phosphatase

ECM:

Extracellular matrix

IL:

Interleukin

NG2:

Neuronal/glial chondroitin sulphate proteoglycan

NGF:

Nerve growth factor

NO:

Nitrogen monoxide

PAI-1:

Plasminogen activator inhibitor

PDGF:

Platelet derived growth factor

PDGFR-β:

Platelet derived growth factor receptor β

SEM:

Scanning electron micrograph

SMC:

Smooth muscle cells

TGF-β:

Transforming growth factor

TEM:

Transmission electron microscopy

References

  1. Andreeva ER, Pugach IM, Gordon D, Orekhov AN (1998) Continuous subendothelial network formed by pericyte-like cells in human vascular bed. Tissue & cell 30(1):127–135

    Article  CAS  Google Scholar 

  2. Armulik A, Genove G, Betsholtz C (2011) Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell 21(2):193–215. doi:10.1016/j.devcel.2011.07.001

    Article  PubMed  CAS  Google Scholar 

  3. Ausoni S, Sartore S (2009) The cardiovascular unit as a dynamic player in disease and regeneration. Trends Mol Med 15(12):543–552. doi:10.1016/j.molmed.2009.10.002

    Article  PubMed  Google Scholar 

  4. Bagher P, Segal SS (2011) Regulation of blood flow in the microcirculation: role of conducted vasodilation. Acta Physiol (Oxf) 202(3):271–284. doi:10.1111/j.1748-1716.2010.02244.x

    Article  CAS  Google Scholar 

  5. Becerra J, Santos-Ruiz L, Andrades JA, Mari-Beffa M (2011) The stem cell niche should be a key issue for cell therapy in regenerative medicine. Stem Cell Rev 7(2):248–255. doi:10.1007/s12015-010-9195-5

    Article  PubMed  Google Scholar 

  6. Bonkowski D, Katyshev V, Balabanov RD, Borisov A, Dore-Duffy P (2011) The CNS microvascular pericyte: Pericyte-astrocyte crosstalk in the regulation of tissue survival. Fluids Barriers CNS 8(1):8. doi:10.1186/2045-8118-8-8

    Article  PubMed  Google Scholar 

  7. Bostrom K, Watson KE, Horn S, Wortham C, Herman IM, Demer LL (1993) Bone morphogenetic protein expression in human atherosclerotic lesions. J Clin Invest 91(4):1800–1809. doi:10.1172/JCI116391

    Article  PubMed  CAS  Google Scholar 

  8. Canfield AE, Doherty MJ, Wood AC, Farrington C, Ashton B, Begum N, Harvey B, Poole A, Grant ME, Boot-Handford RP (2000) Role of pericytes in vascular calcification: A review. Z Kardiol 89(Suppl 2):20–27

    Article  PubMed  Google Scholar 

  9. Chen CW, Montelatici E, Crisan M, Corselli M, Huard J, Lazzari L, Peault B (2009) Perivascular multi-lineage progenitor cells in human organs: regenerative units, cytokine sources or both? Cytokine Growth Factor Rev 20(5–6):429–434. doi:10.1016/j.cytogfr.2009.10.014

    Article  PubMed  CAS  Google Scholar 

  10. Corselli M, Chen CW, Crisan M, Lazzari L, Peault B (2010) Perivascular ancestors of adult multipotent stem cells. Arterioscler Thromb Vasc Biol 30(6):1104–1109. doi:10.1161/ATVBAHA.109.191643

    Article  PubMed  CAS  Google Scholar 

  11. del Zoppo GJ (2010) The neurovascular unit, matrix proteases, and innate inflammation. Annals of the New York Academy of Sciences 1207:46–49. doi:10.1111/j.1749-6632.2010.05760.x

    Article  PubMed  Google Scholar 

  12. Dore-Duffy P (2008) Pericytes: pluripotent cells of the blood brain barrier. Curr Pharm Des 14(16):1581–1593

    Article  PubMed  CAS  Google Scholar 

  13. Eberth CJ (1871) Handbuch der Lehre von den Geweben des Menschen und der Tiere, Vol 1. Leipzig

  14. Edgley AJ, Krum H, Kelly DJ (2012) Targeting fibrosis for the treatment of heart failure: A role for transforming growth factor-beta. Cardiovasc Ther 30(1):e30–40. doi:10.1111/j.1755-5922.2010.00228.x

    Article  PubMed  CAS  Google Scholar 

  15. Finn AV, Nakano M, Narula J, Kolodgie FD, Virmani R (2010) Concept of vulnerable/unstable plaque. Arterioscler Thromb Vasc Biol 30(7):1282–1292. doi:10.1161/ATVBAHA.108.179739

    Article  PubMed  CAS  Google Scholar 

  16. Gharaibeh B, Lavasani M, Cummins JH, Huard J (2011) Terminal differentiation is not a major determinant for the success of stem cell therapy—cross-talk between muscle-derived stem cells and host cells. Stem Cell Res Ther 2(4):31. doi:10.1186/scrt72

    Article  PubMed  Google Scholar 

  17. Gherghiceanu M, Popescu LM (2012) Cardiac telocytes—their junctions and functional implications. Cell Tissue Res 348(2):265–279. doi:10.1007/s00441-012-1333-8

    Article  PubMed  CAS  Google Scholar 

  18. Ghosh AK, Vaughan DE (2012) PAI-1 in tissue fibrosis. J Cell Physiol 227(2):493–507. doi:10.1002/jcp.22783

    Article  PubMed  CAS  Google Scholar 

  19. Han DG (2010) The innateness of coronary artery: vasa vasorum. Med Hypotheses 74(3):443–444. doi:10.1016/j.mehy.2009.10.001

    Article  PubMed  Google Scholar 

  20. Juchem G, Weiss DR, Gansera B, Kemkes BM, Mueller-Hoecker J, Nees S (2010) Pericytes in the macrovascular intima: possible physiological and pathogenetic impact. Am J Physiol Heart Circ Physiol 298(3):H754–770. doi:10.1152/ajpheart.00343.2009

    Article  PubMed  CAS  Google Scholar 

  21. Juchem G, Weiss DR, Knott M, Senftl A, Forch S, Fischlein T, Kreuzer E, Reichart B, Laufer S, Nees S (2012) Regulation of coronary venular barrier function by blood borne inflammatory mediators and pharmacological tools: insights from novel microvascular wall models. Am J Physiol Heart Circ Physiol 302(3):H567–581. doi:10.1152/ajpheart.00360.2011

    Article  PubMed  CAS  Google Scholar 

  22. Karantalis V, Balkan W, Schulman IH, Hatzistergos KE, Hare JM (2012) Cell-based therapy for prevention and reversal of myocardial remodeling. Am J Physiol Heart Circ Physiol 303(3):H256–270. doi:10.1152/ajpheart.00221.2012

    Article  PubMed  CAS  Google Scholar 

  23. Katare R, Riu F, Mitchell K, Gubernator M, Campagnolo P, Cui Y, Fortunato O, Avolio E, Cesselli D, Beltrami AP, Angelini G, Emanueli C, Madeddu P (2011) Transplantation of human pericyte progenitor cells improves the repair of infarcted heart through activation of an angiogenic program involving micro-RNA-132. Circ Res 109(8):894–906. doi:10.1161/CIRCRESAHA.111.251546

    Article  PubMed  CAS  Google Scholar 

  24. Kim JA, Tran ND, Li Z, Yang F, Zhou W, Fisher MJ (2006) Brain endothelial hemostasis regulation by pericytes. J Cereb Blood Flow Metab 26(2):209–217. doi:10.1038/sj.jcbfm.9600181

    Article  PubMed  Google Scholar 

  25. Kutcher ME, Herman IM (2009) The pericyte: cellular regulator of microvascular blood flow. Microvasc Res 77(3):235–246. doi:10.1016/j.mvr.2009.01.007

    Article  PubMed  CAS  Google Scholar 

  26. McCullough PA, Olobatoke A, Vanhecke TE (2011) Galectin-3: a novel blood test for the evaluation and management of patients with heart failure. Rev Cardiovasc Med 12(4):200–210. doi:10.3909/ricm0624

    PubMed  Google Scholar 

  27. Muller JM, Davis MJ, Chilian WM (1996) Integrated regulation of pressure and flow in the coronary microcirculation. Cardiovasc Res 32(4):668–678

    PubMed  CAS  Google Scholar 

  28. Murakami M, Simons M (2009) Regulation of vascular integrity. J Mol Med (Berl) 87(6):571–582. doi:10.1007/s00109-009-0463-2

    Article  Google Scholar 

  29. Murshed M, McKee MD (2010) Molecular determinants of extracellular matrix mineralization in bone and blood vessels. Curr Opin Nephrol Hypertens 19(4):359–365. doi:10.1097/MNH.0b013e3283393a2b

    Article  PubMed  CAS  Google Scholar 

  30. Nees S, Herzog V, Becker BF, Bock M, Des Rosiers C, Gerlach E (1985) The coronary endothelium: a highly active metabolic barrier for adenosine. Basic Res Cardiol 80(5):515–529

    Article  PubMed  CAS  Google Scholar 

  31. Nees S, Juchem G, Eberhorn N, Thallmair M, Forch S, Knott M, Senftl A, Fischlein T, Reichart B, Weiss DR (2012) Wall structures of myocardial precapillary arterioles and postcapillary venules reexamined and reconstructed in vitro for studies on barrier functions. Am J Physiol Heart Circ Physiol 302(1):H51–68. doi:10.1152/ajpheart.00358.2011

    Article  PubMed  CAS  Google Scholar 

  32. Nees S, Juchem G, Weiss DR, Partsch H (2012) Pathogenesis and therapy of chronic venous disease: new insights into structure and function of the leg venous system. Phlebologie 41:246–257

    Google Scholar 

  33. Nees S, Weiss DR, Senftl A, Knott M, Forch S, Schnurr M, Weyrich P, Juchem G (2012) Isolation, bulk cultivation, and characterization of coronary microvascular pericytes: the second most frequent myocardial cell type in vitro. Am J Physiol Heart Circ Physiol 302(1):H69–84. doi:10.1152/ajpheart.00359.2011

    Article  PubMed  CAS  Google Scholar 

  34. Osterud B, Bjorklid E (2006) Sources of tissue factor. Semin Thromb Hemost 32(1):11–23. doi:10.1055/s-2006-933336

    Article  PubMed  Google Scholar 

  35. Pober JS, Tellides G (2012) Participation of blood vessel cells in human adaptive immune responses. Trends Immunol 33(1):49–57. doi:10.1016/j.it.2011.09.006

    Article  PubMed  CAS  Google Scholar 

  36. Popescu LM, Faussone-Pellegrini MS (2010) TELOCYTES—a case of serendipity: the winding way from Interstitial Cells of Cajal (ICC), via Interstitial Cajal-Like Cells (ICLC) to TELOCYTES. Journal of cellular and molecular medicine 14(4):729–740. doi:10.1111/j.1582-4934.2010.01059.x

    Article  PubMed  CAS  Google Scholar 

  37. Poston RS, Gu J, Brown JM, Gammie JS, White C, Nie L, Pierson RN 3rd, Griffith BP (2006) Endothelial injury and acquired aspirin resistance as promoters of regional thrombin formation and early vein graft failure after coronary artery bypass grafting. The Journal of thoracic and cardiovascular surgery 131(1):122–130. doi:10.1016/j.jtcvs.2005.08.058

    Article  PubMed  Google Scholar 

  38. Proebstl D, Voisin MB, Woodfin A, Whiteford J, D'Acquisto F, Jones GE, Rowe D, Nourshargh S (2012) Pericytes support neutrophil subendothelial cell crawling and breaching of venular walls in vivo. J Exp Med 209(6):1219–1234. doi:10.1084/jem.20111622

    Article  PubMed  CAS  Google Scholar 

  39. Ribatti D, Crivellato E (2012) “Sprouting angiogenesis”, a reappraisal. Dev Biol 372(2):157–165. doi:10.1016/j.ydbio.2012.09.018

    Article  PubMed  CAS  Google Scholar 

  40. Rusu MC, Pop F, Hostiuc S, Curca GC, Jianu AM, Paduraru D (2012) Telocytes form networks in normal cardiac tissues. Histol Histopathol 27(6):807–816

    PubMed  CAS  Google Scholar 

  41. Sa-Pereira I, Brites D, Brito MA (2012) Neurovascular unit: a focus on pericytes. Mol Neurobiol 45(2):327–347. doi:10.1007/s12035-012-8244-2

    Article  PubMed  CAS  Google Scholar 

  42. Siao CJ, Lorentz CU, Kermani P, Marinic T, Carter J, McGrath K, Padow VA, Mark W, Falcone DJ, Cohen-Gould L, Parrish DC, Habecker BA, Nykjaer A, Ellenson LH, Tessarollo L, Hempstead BL (2012) ProNGF, a cytokine induced after myocardial infarction in humans, targets pericytes to promote microvascular damage and activation. J Exp Med 209(12):2291–2305. doi:10.1084/jem.20111749

    Article  PubMed  CAS  Google Scholar 

  43. Socha MJ, Behringer EJ, Segal SS (2012) Calcium and electrical signalling along endothelium of the resistance vasculature. Basic & clinical pharmacology & toxicology 110(1):80–86. doi:10.1111/j.1742-7843.2011.00798.x

    Article  CAS  Google Scholar 

  44. Tijsen AJ, Pinto YM, Creemers EE (2012) Non-cardiomyocyte microRNAs in heart failure. Cardiovasc Res 93(4):573–582. doi:10.1093/cvr/cvr344

    Article  PubMed  CAS  Google Scholar 

  45. Vanhoutte PM, Shimokawa H, Tang EH, Feletou M (2009) Endothelial dysfunction and vascular disease. Acta Physiol (Oxf) 196(2):193–222. doi:10.1111/j.1748-1716.2009.01964.x

    Article  CAS  Google Scholar 

  46. Wang S, Cao C, Chen Z, Bankaitis V, Tzima E, Sheibani N, Burridge K (2012) Pericytes regulate vascular basement membrane remodeling and govern neutrophil extravasation during inflammation. PLoS One 7(9):e45499. doi:10.1371/journal.pone.0045499

    Article  PubMed  CAS  Google Scholar 

  47. Weiss DR, Juchem G, Kemkes BM, Gansera B, Nees S (2009) Extensive deendothelialization and thrombogenicity in routinely prepared vein grafts for coronary bypass operations: facts and remedy. Int J Clin Exp Med 2(2):95–113

    PubMed  CAS  Google Scholar 

  48. Whyte MP (2010) Physiological role of alkaline phosphatase explored in hypophosphatasia. Annals of the New York Academy of Sciences 1192:190–200. doi:10.1111/j.1749-6632.2010.05387.x

    Article  PubMed  CAS  Google Scholar 

  49. Zimmermann KW (1923) Der feinere Bau der Blutcapillaren. Zeitschr f d ges Anat 68:29–109

    Article  Google Scholar 

Download references

Acknowledgments

We thank Barbara Nees for excellent pictorial design and photographic work.

Author information

Authors and Affiliations

  1. Department of Physiology, University of Munich (LMU), Schillerstr. 44, 80336, Munich, Germany

    Stephan Nees

  2. Department of Transfusion Medicine and Hemostaseology, University of Erlangen-Nuremberg (FAU), 91054, Erlangen, Germany

    Dominik R. Weiss

  3. Department of Cardiac Surgery, University of Munich (LMU), 81377, Munich, Germany

    Gerd Juchem

Authors
  1. Stephan Nees
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dominik R. Weiss
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gerd Juchem
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stephan Nees.

Electronic Supplementary Materials

Below is the link to the electronic supplementary material.

ESM 1

(DOCX 16 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nees, S., Weiss, D.R. & Juchem, G. Focus on cardiac pericytes. Pflugers Arch - Eur J Physiol 465, 779–787 (2013). https://doi.org/10.1007/s00424-013-1240-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-013-1240-1

Keywords

Search

Navigation