Stimulation of Arterial Smooth Muscle Cell Proliferation by Remnant Lipoprotein Particles Isolated by Immuno-Affinity Chromatography with Anti-apo A-I and Anti-apo B-100

Abstract

Postprandial lipidemia, characterized by high plasma triglyceride-rich lipoprotein remnants, is associated with atherosclerosis. It has also been known that proliferation of vascular smooth muscle cells is crucial for the development of atherosclerosis. In this study, we investigated the direct effect of remnant lipoprotein particles, which consist of chylomicron remnants and very low density lipoprotein remnants, on vascular smooth muscle cell proliferation. Blood was collected from six patients with postprandial lipidemia two hours after their usual meal. Remnant lipoprotein particles were isolated from plasma by immuno-affinity chromatography containing two monoclonal antibodies, anti-apo A-I (H-12) and anti-apo B-100 (JI-H). Remnant lipoprotein particles, as well as betaVLDL, significantly stimulated the proliferation of porcine coronary artery smooth muscle cells in a concentration-dependent manner, whereas very low density lipoprotein (d < 1.006) was virtually ineffective. These observations are consistent with recent reports that triglyceride-rich lipoprotein remnants, which are rich in apo E as well, are atherogenic.

Remnant Lipoproteins and Atherogenesis

“…However, the direct effects of RLPs on smooth muscle cell (SMC) have remained almost unknown. We reported for the first time that RLPs induced SMC proliferation, regardless of its oxidative stress (13), and more recently identified the molecular mechanisms by which RLPs induce proliferation of vascular SMCs (14). In the latter, we reported that RLPs from hypertriglyceridemic (HTG) patients stimulated SMC proliferation via epidermal growth factor (EGF) receptor transactivation and heparin-binding EGF-like growth factor (HB-EGF) shedding.…”

Remnant Lipoprotein-Induced Smooth Muscle Cell Proliferation Involves Epidermal Growth Factor Receptor Transactivation

“…However, the direct effects of RLPs on SMCs in media have not been fully elucidated, although we recently showed that RLPs directly stimulate porcine coronary artery SMC proliferation, independent of oxidative stress. 2 In line with those results, we examined the effects of RLPs on MAPK pathway and epidermal growth factor (EGF) receptor transactivation, along with the involvement of G protein-coupled receptor in rat aortic SMCs. Herein, we report for the first time that atherogenic RLPs from patients with hypertriglyceridemia stimulated rat SMC proliferation via heparin-binding EGF-like growth factor (HB-EGF) shedding and EGF receptor transactivation.…”

“…1 Our previous results have also suggested a causative role of RLPs in atherosclerosis. 2,3 The proliferation of smooth muscle cells (SMCs) plays a critical role in intimal thickening of arteries associated with atherosclerosis or restenosis after percutaneous coronary intervention (PCI). 4 Several lipoproteins have been reported to induce the migration and proliferation of SMCs via activation of mitogen-activated protein kinase (MAPK), in which G protein-coupled receptor (GPCR)-dependent protein kinase C (PKC) activation was shown to be involved.…”

Remnant Lipoproteins As Strong Key Particles to Atherogenesis

“…-VLDL induced SMC proliferation by activation of MAPK via G protein-coupled receptor-mediated transactivation of the epidermal growth factor (EGF) receptor 73) . Kawakami et al reported that RLP from hypertriglyceridemic patients induced SMC proliferation 74,75) .…”