Skip to main content

Mast cells in atherogenesis: Actions and reactions

Current Atherosclerosis Reports volume 11, pages 214–219 (2009)Cite this article

Abstract

Mast cells (better known as allergy cells) are pro-inflammatory effector cells present in the human arterial intima and in evolving atherosclerotic lesions. Experiments in vitro, in vivo experiments in animals, and immunohistologic studies of human coronary samples have uncovered mechanisms by which activated mast cells could participate in the development of the lesions. When activated, mast cells acutely expel a fraction of their cytoplasmic granules, which are filled with a wide selection of heparin-bound preformed mediators. These include histamine, neutral proteases, growth factors, and proinflammatory cytokines. The microenvironmental targets of these effector molecules are various lipoprotein particles in the intimal fluid, components of the extracellular matrix, and intimal cells neighboring the activated mast cells. Importantly, sustained selective release of proinflammatory mediators without degranulation may also occur at sites of chronic inflammation. The activities of the various mediators are suggested to contribute to fatty streak formation and to the generation of unstable plaques susceptible to rupture. Thus, mast cells appear to provide a novel link between inflammation and atherogenesis.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References and Recommended Reading

  1. Hansson GK: Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005, 352:1685–1695.

    Article  CAS  PubMed  Google Scholar 

  2. Kovanen PT: Mast cells: multipotent local effector cells in atherothrombosis. Immunol Rev 2007, 217:105–122.

    Article  CAS  PubMed  Google Scholar 

  3. Tabas I, Williams KJ, Borén J: Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation 2007, 116:1832–1844.

    Article  CAS  PubMed  Google Scholar 

  4. Kelley J, Hemontolor G, Younis W, et al.: Mast cell activation by lipoproteins. Methods Mol Biol 2006, 315:341–348.

    PubMed  Google Scholar 

  5. Lindstedt KA, Mäyränpää MI, Kovanen PT: Mast cells in vulnerable atherosclerotic plaques—a view to a kill. J Cell Mol Med 2007, 11:739–758.

    Article  CAS  PubMed  Google Scholar 

  6. Mäyränpää MI, Heikkil: Desquamation of human coronary artery endothelium by human mast cell proteases: implications for plaque erosion. Coronary Artery Dis 2006, 17:611–621.

    Article  Google Scholar 

  7. Miyamoto T, Sasaguri Y, Sasaguri T, et al.: Expression of stem cell factor in human aortic endothelial and smooth muscle cells. Atherosclerosis 1997, 129:207–213.

    Article  CAS  PubMed  Google Scholar 

  8. Haley KJ, Lilly CM, Yang JH, et al.: Overexpression of eotaxin and the CCR3 receptor in human atherosclerosis: using genomic technology to identify a potential novel pathway of vascular inflammation. Circulation 2000, 102:2185–2189.

    CAS  PubMed  Google Scholar 

  9. Galli SJ, Nakae S, Tsai M: Mast cells in the development of adaptive immune responses. Nat Immunol 2005, 6:135–142.

    Article  CAS  PubMed  Google Scholar 

  10. Laine P, Kaartinen M, Penttil: Association between myocardial infarction and the mast cells in the adventitia of the infarct-related coronary artery. Circulation 1999, 99:361–369.

    CAS  PubMed  Google Scholar 

  11. Lappalainen H, Laine P, Pentikäinen MO, et al.: Mast cells in neovascularized human coronary plaques store and secrete basic fibroblast growth factor, a potent angiogenic mediator. Arterioscler Thromb Vasc Biol 2004, 24:1880–1885.

    Article  CAS  PubMed  Google Scholar 

  12. Stevens RL, Adachi R: Protease-proteoglycan complexes of mouse and human mast cells and importance of their betatryptase-heparin complexes in inflammation and innate immunity. Immunol Rev 2007, 217:155–167.

    Article  CAS  PubMed  Google Scholar 

  13. Lappalainen J, Lindstedt KA, Kovanen PT: A protocol for generating high numbers of mature and functional human mast cells from peripheral blood. Clin Exp Allergy 2007, 37:1404–1412.

    Article  CAS  PubMed  Google Scholar 

  14. Irani AA, Craig SS, Nilsson G, et al.: Characterization of human mast cells developed in vitro from fetal liver cells cocultured with murine 3T3 fibroblasts. Immunology 1992, 77:136–143.

    CAS  PubMed  Google Scholar 

  15. Galli SJ, Kalesnikoff J, Grimbaldeston MA, et al.: Mast cells as “tunable” effector and immunoregulatory cells: recent advances. Annu Rev Immunol 2005, 23:749–786.

    Article  CAS  PubMed  Google Scholar 

  16. Kaartinen M, Penttil: Mast cells in rupture-prone areas of human coronary atheromas produce and store TNF-alpha. Circulation 1996, 94:2787–2792.

    CAS  PubMed  Google Scholar 

  17. Kovanen PT, Kaartinen M, Paavonen T: Infiltrates of activated mast cells at the site of coronary atheromatous erosion or rupture in myocardial infarction. Circulation 1995, 92:1084–1088.

    CAS  PubMed  Google Scholar 

  18. Galli SJ, Dvorak AM, Dvorak HF: Basophils and mast cells: morphologic insights into their biology, secretory patterns, and function. Prog Allergy 1984, 34:1–141.

    CAS  PubMed  Google Scholar 

  19. Kawakami T, Galli SJ: Regulation of mast-cell and basophil function and survival by IgE. Nat Rev Immunol 2002, 2:773–786.

    Article  CAS  PubMed  Google Scholar 

  20. Kounis NG: Kounis syndrome (allergic angina and allergic myocardial infarction): a natural paradigm? Int J Cardiol 2006, 110:7–14.

    Article  PubMed  Google Scholar 

  21. Kovanen PT: Mast cells and degradation of pericellular and extracellular matrices: potential contributions to erosion, rupture and intraplaque haemorrhage of atherosclerotic plaques. Biochem Soc Trans 2007, 35:857–861.

    Article  CAS  PubMed  Google Scholar 

  22. Kaartinen M, Penttil Kovanen PT: Extracellular mast cell granules carry apolipoprotein B-100-containing lipoproteins into phagocytes in human arterial intima: functional coupling of exocytosis and phagocytosis in neighboring cells. Arterioscler Thromb Vasc Biol 1995, 15:2047–2054.

    CAS  PubMed  Google Scholar 

  23. Dvorak AM: Piecemeal degranulation of basophils and mast cells is effected by vesicular transport of stored secretory granule contents. Chem Immunol Allergy 2005, 85:135–184.

    Article  PubMed  Google Scholar 

  24. Gordon JR, Galli SJ: Mast cells as a source of both preformed and immunologically inducible TNF-alpha/cachectin. Nature 1990, 346:274–276.

    Article  CAS  PubMed  Google Scholar 

  25. Theoharides TC, Kempuraj D, Tagen M, et al.: Differential release of mast cell mediators and the pathogenesis of inflammation. Immunol Rev 2007, 217:65–78.

    Article  CAS  PubMed  Google Scholar 

  26. Fischer M, Harvima IT, Carvalho RF, et al.: Mast cell CD30 ligand is upregulated in cutaneous inflammation and mediates degranulation-independent chemokine secretion. J Clin Invest 2006, 116:2748–2756.

    Article  CAS  PubMed  Google Scholar 

  27. Boyle JJ: Association of coronary plaque rupture and atherosclerotic inflammation. J Pathol 1997, 181:93–99.

    Article  CAS  PubMed  Google Scholar 

  28. Boyce JA: Mast cells and eicosanoid mediators: a system of reciprocal paracrine and autocrine regulation. Immunol Rev 2007, 217:168–185.

    Article  CAS  PubMed  Google Scholar 

  29. Bäck M, Hansson GK: Leukotriene receptors in atherosclerosis. Ann Med 2006, 38:493–502.

    Article  PubMed  Google Scholar 

  30. Bachelet I, Levi-Schaffer F, Mekori YA: Mast cells: not only in allergy. Immunol Allergy Clin North Am 2006, 26:407–425.

    Article  PubMed  Google Scholar 

  31. Oksjoki R, Kovanen PT, Meri S, Pentikäinen MO: Function and regulation of the complement system in cardiovascular diseases. Front Biosci 2007, 12:4696–4708.

    Article  CAS  PubMed  Google Scholar 

  32. Oksjoki R, Laine P, Helske S, et al.: Receptors for the anaphylatoxin C3aR and C5aR are expressed in human atherosclerotic coronary plaques. Atherosclerosis 2007, 195:90–99.

    Article  CAS  PubMed  Google Scholar 

  33. Baumann U, Chouchakova N, Gewecke B, et al.: Distinct tissue site-specific requirements of mast cells and complement components C3/C5a receptor in IgG immune complex-induced injury of skin and lung. J Immunol 2001, 167:1022–1027.

    CAS  PubMed  Google Scholar 

  34. Ylä-Herttuala S, Palinski W, Butler SW, et al.: Rabbit and human atherosclerotic lesions contain IgG that recognizes epitopes of oxidized LDL. Arterioscler Thromb 1994, 14:32–40.

    PubMed  Google Scholar 

  35. Ma H, Kovanen PT: Degranulation of cutaneous mast cells induces transendothelial transport and local accumulation of plasma LDL in rat skin in vivo. J Lipid Res 1997, 38:1877–1887.

    CAS  PubMed  Google Scholar 

  36. Kokkonen JO: Stimulation of rat peritoneal mast cells enhances uptake of low density lipoproteins by rat peritoneal macrophages in vivo. Atherosclerosis 1989, 79:213–223.

    Article  CAS  PubMed  Google Scholar 

  37. Lee-Rueckert M, Kovanen PT: Mast cell proteases: physiological tools to study functional significance of high density lipoproteins in the initiation of reverse cholesterol transport. Atherosclerosis 2006, 189:8–18.

    Article  CAS  PubMed  Google Scholar 

  38. Libby P, Shi GP: Mast cells as mediators and modulators of atherogenesis. Circulation 2007, 115:2471–2473.

    Article  PubMed  Google Scholar 

  39. Sun J, Sukhova GK, Wolters PJ, et al.: Mast cells promote atherosclerosis by releasing proinflammatory cytokines. Nat Med 2007, 13:719–724.

    Article  CAS  PubMed  Google Scholar 

  40. Bot I, de Jager SC, Zernecke A, et al.: Perivascular mast cells promote atherogenesis and induce plaque destabilization in apolipoprotein E-deficient mice. Circulation 2007, 115:2516–2525.

    Article  CAS  PubMed  Google Scholar 

  41. Metz M, Grimbaldeston MA, Nakae S, et al.: Mast cells in the promotion and limitation of chronic inflammation. Immunol Rev 2007, 217:304–328.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Affiliations

  1. Wihuri Research Institute, Kalliolinnantie 4, 00140, Helsinki, Finland

    Petri T. Kovanen

Authors
  1. Petri T. Kovanen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Petri T. Kovanen.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kovanen, P.T. Mast cells in atherogenesis: Actions and reactions. Curr Atheroscler Rep 11, 214–219 (2009). https://doi.org/10.1007/s11883-009-0033-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11883-009-0033-7

Keywords

  • Mast Cell
  • Atherosclerotic Lesion
  • Stem Cell Factor
  • Tryptase
  • Activate Mast Cell