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J Thorac Cardiovasc Surg 2001;121:820
© 2001 The American Association for Thoracic Surgery

Letters to the Editor

Vascular endothelial cell is a stem cell for neointimal formation after injury

Jiri T. Beranek, MD

4101 S. Wappel Dr Columbia, MO 65203

To the Editor:

Hosono and associatesGo 1 used immunohistochemical techniques for the identification of smooth muscle cells and macrophages in neointimal formations at the anastomoses of internal thoracic artery grafts with coronary arteries after bypass grafting in human beings. For the simultaneous identification of both cell types, they used a double staining method with monoclonal antibodies HHF-35 identifying muscle actin and HAM-56 recognizing macrophages. Having evaluated the results, they overlooked those cells that manifested both markers. Notice in their Fig 4, A and B, that numerous red-staining macrophage-like cells manifest small turquoise spots in their cytoplasm, evidencing small fascicles of muscle fibrils. Note also in Fig 4, C, that the number of macrophage-like cells has diminished and that the remaining ones manifest a higher amount of muscle fibrils than those in Fig 4, A and B, suggesting that the extinct macrophage-like cells have not disappeared by necrosis, apoptosis, or egress but by transdifferentiation into smooth muscle cells.

The above observation does not split hairs but concerns the fundamental question of postinjury neointimal formation: What is the origin of new smooth muscle cells? This question is particularly important because it bears on the most frequent disease in humankind: atherosclerosis.Go 2 The irony of this situation is that there are few candidates for such a stem cell: medial smooth muscle cells, vascular endothelial cells, and adventitial fibroblasts.Go 3 In my opinion, medial smooth muscle cells and adventitial fibroblasts may be excluded because they do not express macrophagic markers. The only cells able to produce collagens and to manifest macrophagic and muscle markers are vascular endothelial cells.Go Go 2-4 It is plausible, therefore, that the cells manifesting both macrophagic and muscle markers in Fig 4, A and B,Go 1 have derived from vascular endothelial cells and that they have given birth to fully differentiated smooth muscle cells present in Fig 6, B.Go 1 These data support the hypothesis that the vascular endothelial cell is a stem cell for neointimal formations after injury.Go 2 Having said that, I do not deny a widely known influx of genuine monocytes into the injured vascular wall. On the contrary, I believe this influx camouflages the presence of "myohistiocytes," that is, vascular endothelial cell derivatives in neointimal formations.

Neointimal cells manifesting both muscle actin and macrophagic markers have already been observed in rabbit cardiac allograft atherosclerosis, rabbit hyperlipidemic atherosclerosis, and human atherosclerosis.Go 5

12/8/113931doi:10.1067/mtc.2001.113931

References

  1. Hosono M, Ueda M, Suehiro S, Sasaki Y, Shibata T, Hattori K, et al. Neointimal formation at the sites of anastomosis of the internal thoracic artery grafts after coronary artery bypass grafting in human subjects: an immunohistochemical analysis. J Thorac Cardiovasc Surg 2000;120:319-28.[Abstract/Free Full Text]
  2. Beranek JT. Atherosclerosis: a personal view. Card Chronicle 1991;5(9):1-6.
  3. Gittenberger-de Groot AC, DeRuiter MC, Bergwerff M, Poelman RE. Smooth muscle cell origin and its relation to heterogeneity in development and disease. Arterioscler Thromb Vasc Biol 1999;19:1589-94.[Free Full Text]
  4. Lipton BH, Bensch KG, Karasek MA. Microvessel endothelial cell transdifferentiation: phenotypic characterization. Differentiation 1991;46:117-33.[Medline]
  5. Beranek JT, Cavarocchi NC. Smooth muscle cells and macrophages in rabbit cardiac allograft atherosclerosis. J Heart Transplant 1990;9:732.[Medline]




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