Thrombospondin-1 activates medial smooth muscle cells and triggers neointima formation upon mouse carotid artery ligation.

Content Provider	Semantic Scholar
Author	Moura, Rute Tjwa, Marc Vandervoort, Petra A. H. Cludts, Katrien Hoylaerts, Marc F.
Copyright Year	2007
Abstract	OBJECTIVE Thrombospondin-1 (TSP1) is described as a positive regulator of vascular smooth muscle growth in cell culture. However, insight into the in vivo effects of TSP1 on smooth muscle cell (SMC) function is lacking. METHODS AND RESULTS We analyzed wild-type (WT) and TSP1-deficient (Tsp1-/-) mice in a carotid artery ligation model, in which neointimal lesions form without overt mechanical damage to the endothelium. On ligation, the expression of TSP1 increased strongly in the matrix of neointima and adventitia. In the early phase after ligation (day 3 to 7), activation, proliferation, and migration of medial SMCs were delayed and impaired in Tsp1-/- mice, in parallel with defective upregulation of metalloproteinase (MMP)-2 activity. As a result, Tsp1-/- arteries developed smaller neointimal lesions, a thicker media but comparably attenuated patency as in WT arteries, 28 days after ligation. Furthermore, medial and neointimal SMCs in Tsp1-/- mice produced more collagen, more osteopontin, and displayed weaker smooth muscle actin staining than WT SMCs, indicative of a modified SMC phenotype in Tsp1-/- mice. CONCLUSIONS Arterial SMC activation in the absence of TSP1 is delayed and dysregulated, reducing neointima formation, on mild vascular injury.
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Alternate Webpage(s)	http://atvb.ahajournals.org/content/atvbaha/27/10/2163.full.pdf?download=true
PubMed reference number	17761938v1
Volume Number	27
Issue Number	10
Journal	Arteriosclerosis, thrombosis, and vascular biology
Language	English
Access Restriction	Open
Subject Keyword	Adventitia Arterial system Carotid Arteries Cell Culture Techniques Ligation Metalloproteases Muscle Cells Muscle, Smooth, Vascular Myocytes, Smooth Muscle Neointima Precipitating Factors Small Smooth muscle (tissue) Staining method Thrombospondin 1 Vascular System Injuries
Content Type	Text
Resource Type	Article