The role of apolipoprotein D in vascular smooth muscle cell proliferation

Smooth muscle cell proliferation is a key feature in vascular diseases such as atherosclerosis, restenosis post angioplasty and pulmonary hypertension. A rise in apolipoprotein D (apoD), a small component of high density lipoprotein, is associated with inhibition of cancer cell proliferation. We investigated the role of apoD on vascular smooth muscle cell (VSMC) proliferation. Using rat A10 VSMC, which do not synthesize apoD, we expressed human apoD through transfection. While endogenous apoD expression had no effect on VSMC proliferation, exogenous application of apoD inhibited platelet derived growth factor (PDGF) induced proliferation in a dose-dependent manner. This was not achieved through inhibition of PDGF activation of mitogen activated protein kinase ERK1/2 or by induction of cell cycle inhibitors p21 or p27. While apoD is associated with the leptin receptor in the hypothalamus, no functional interaction of these proteins was demonstrated in VSMC to explain the inhibition of PDGF mediated VSMC proliferation.