The more the merrier: Severe vascular injury increases engagement of smooth muscle cell clones in intimal repair

Vessel wall healing in response to mechanical trauma was first described by Alexis Carell in 1906, who observed regeneration of tissue on top of the suture-line in a vascular anastomosis [ [1] Carrel A. Guthrie C.C. Anastomosis of blood vessels by the patching method and transplantation of the kidney. JAMA. 1906; 47: 1648-1651 Crossref Google Scholar ]. Clinically, this observation was later to become of relevance for numerous human vascular disease conditions, especially after surgical procedures in restenosis, vein graft stenosis and in transplant vasculopathy with chronic organ rejection, but also with respect to fibrous cap integrity in atherosclerotic plaque stability [ [2] Hedin U. Roy J. Tran P.K. Smooth muscle cell proliferation in vascular disease. Curr. Opin. Lipidol. 2004; 15: 559-565 Crossref PubMed Scopus (69) Google Scholar ]. However, the phenomenon was not explored in more detail until the late 1960's, when a decade of research in several animal models led to a comprehensive understanding of vascular repair and formation of intimal hyperplasia after mechanical trauma [ [3] Björkerud S. Reaction of the aortic wall of the rabbit after superficial, longitudinal, mechanical trauma. Virchows Arch. [Pathol Anat]. 1969; 347: 197-210 Crossref PubMed Scopus (0) Google Scholar , [4] Stemerman M.B. Ross R. Experimental arteriosclerosis: I. Fibrous plaque formation in primates, an electron microscope study. J. Exp. Med. 1972; 136: 769-789 Crossref PubMed Google Scholar ], including the identification of a central role for medial smooth muscle cells (SMCs) in the repair process [ 5 Spaet T.H. Stemerman M.B. Veith F.J. Lejnieks I. Intimal injury and regrowth in the rabbit aorta: medial smooth muscle cells as a source of neointima. Circ. Res. 1975; 36: 58-70 Crossref PubMed Scopus (0) Google Scholar , 6 Schwartz S.M. Stemerman M.B. Benditt E.P. The aortic intima: I. Repair of the aortic lining after mechanical denudation. Am. J. Pathol. 1975; 81: 15-42 PubMed Google Scholar , 7 Clowes A.W. Reidy M.A. Clowes M.M. Mechanisms of stenosis after arterial injury. Lab. Invest. 1983; 49: 208-215 PubMed Google Scholar ]. Even if mechanical trauma has been the most investigated trigger of SMC activation in the formation of intimal hyperplasia, any stress (mechanical, inflammatory, chemical, hemodynamic) inflicted on the vessel with or without endothelial cell denudation, may lead to intimal lesions. In addition, the magnitude of the healing response has also been shown to be determined by the severity of the injury to the vessel wall [ [8] Fingerle J. Au Y.P. Clowes A.W. Reidy M.A. Intimal lesion formation in rat carotid arteries after endothelial denudation in absence of medial injury. Arteriosclerosis. 1990; 10: 1082-1087 Crossref PubMed Google Scholar ]. Severe arterial injury heals with a complex clonal structure involving a large fraction of surviving smooth muscle cellsAtherosclerosisPreviewSmooth muscle cell (SMC) lineage cells in atherosclerosis and flow cessation-induced neointima are oligoclonal, being recruited from a tiny fraction of medial SMCs that modulate and proliferate. The present study aimed to investigate the clonal structure of SMC lineage cells healing more severe arterial injury. Full-Text PDF Open Access