on July 29, 2004
Published online before print July 29, 2004, doi: 10.1161/01.ATV.0000140820.51174.8d
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Submitted on April 19, 2004
Accepted on June 21, 2004
Mast Cells in Neovascularized Human Coronary Plaques Store and Secrete Basic Fibroblast Growth Factor, a Potent Angiogenic Mediator
Helena Lappalainen ;
From the Wihuri Research Institute (H.L., P.L., M.O.P., P.T.K.), Helsinki; the Division of Cardiology (P.L.), Department of Medicine, Helsinki University Central Hospital; and the Department of Forensic Medicine (A.S.), University of Helsinki, Finland.
* To whom correspondence should be addressed. E-mail: petri.kovanen{at}wri.fi.
Objective--Intraplaque neovascularization and hemorrhage may facilitate plaque progression. We studied expression of basic fibroblast growth factor (bFGF), a potent angiogenic mediator, by mast cells (MCs) in human coronary plaques with increasing degrees of atherosclerosis.
Methods and Results--Normal and atherosclerotic coronary segments were collected from 30 autopsied subjects. Immunohistochemical methods were used to detect MCs, bFGF, and microvessels. Both adventitial and intimal MCs showed intracytoplasmic granular staining for bFGF, and bFGF-positive extracellular granules were observed close to the MCs. Increased numbers of bFGF-positive MCs were detected in neovascularized areas of plaques, and there was a positive correlation between numbers of bFGF-positive MCs and microvessels in both the intima and adventitia. In plaques, the highly neovascularized areas contained increased numbers of bFGF-positive MCs compared with the adjacent nonvascularized areas, where only few MCs were present. Importantly, the proportion of intimal MCs expressing bFGF increased with increasing severity of atherosclerosis.
Conclusions--The present work reveals a novel source of bFGF in human coronary arteries, the intimal and adventitial MCs. The association of bFGF-positive MCs with microvessels and with the severity of atherosclerosis suggests that coronary MCs, by releasing bFGF, may play a role in angiogenesis and progression of coronary plaques.
Key words: basic fibroblast growth factor • mast cells • neovascularization • adventitia • atherosclerosis
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