High-density lipoproteins suppress chemokine expression and proliferation in human vascular smooth muscle cells
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Updated: May 15, 2026
A Cell Culture Model of Resistance Arteries
Published on: September 8, 2017
Emiel P C van der Vorst1, Laura Z Vanags, Louise L Dunn
1Heart Research Institute, Newtown, New South Wales, Australia.
Insights
Reconstituted high-density lipoproteins (rHDLs) inhibit vascular smooth muscle cell (SMC) proliferation and chemokine expression by blocking key signaling pathways. This suggests rHDLs may prevent neointimal hyperplasia, a cause of graft and stent failure.
Area of Science:
- Cardiovascular Biology
- Cell Signaling
- Lipoprotein Research
Background:
- Inflammatory chemokines (CCL2, CCL5, CX₃CL1) promote vascular smooth muscle cell (SMC) proliferation.
- High-density lipoproteins (HDLs) possess cardioprotective and anti-inflammatory effects.
Purpose of the Study:
- To investigate the impact of reconstituted HDLs (rHDLs) on SMC chemokine expression and proliferation.
- To elucidate the underlying molecular mechanisms of rHDL action.
Main Methods:
- Primary human SMCs were treated with rHDLs before TNF-α stimulation.
- Assessed protein levels of chemokines, receptors, and signaling molecules (NF-κB, Akt, ERK).
- Utilized siRNA to investigate the role of scavenger receptor SR-B1.
Main Results:
- rHDLs significantly reduced SMC expression of CCL2, CCL5, and CX₃CL1.
- rHDLs inhibited SMC proliferation and phosphorylation of ERK.
- rHDLs suppressed NF-κB and Akt signaling pathways, with SR-B1 mediating these effects.
Conclusions:
- rHDLs decrease SMC chemokine expression via NF-κB and Akt inhibition.
- rHDLs suppress SMC proliferation through ERK pathway inhibition.
- rHDLs offer potential therapeutic benefits against neointimal hyperplasia and vascular graft/stent failure.
Abstract:
The inflammatory chemokines CCL2, CCL5, and CX₃CL1 stimulate vascular smooth muscle cell (SMC) proliferation. High-density lipoproteins (HDLs) exhibit potent cardioprotective and anti-inflammatory properties. We therefore sought to determine the effect of reconstituted HDLs (rHDLs) on SMC chemokine expression and proliferation and elucidate the mechanisms. Preincubation of primary human SMCs with rHDLs containing apolipoprotein (apo)A-I and phosphatidylcholine (20 μM, final apoA-I concentration), before stimulation with TNF-α, inhibited CCL2 (54%), CCL5 (38%), and CX3CL1 (33%) protein levels. The chemokine receptors CCR2 (29%) and CX3CR1 (22%) were also reduced by rHDLs. Incubation with rHDLs reduced the NF-κB subunit p65 in the nucleus (39%) and phosphorylated IκBα (28%), both regulators of chemokine expression. Furthermore, rHDLs inhibited the upstream signaling proteins phosphoinositide 3-kinase (37%) and phosphorylated Akt (pAkt, 49%). Incubation with rHDLs strikingly suppressed SMC proliferation (84%) and ERK phosphorylation (pERK, 29%). Finally, siRNA knockdown of the scavenger receptor SR-B1 attenuated rHDL-induced inhibition of SMC chemokine expression, p65, and proliferation, indicating that SR-B1 plays a key role in mediating these effects. Thus, rHDLs reduce SMC chemokine expression (via NF-κB/pAkt inhibition) and proliferation (via pERK inhibition). This has important implications for preventing the pathogenesis of neointimal hyperplasia, the main cause of early vein graft/stent failure.
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