Acute Changes in Plasma Levels of Hepatocyte Growth Factor During Low‐Density Lipoprotein Apheresis

Abstract

Hepatocyte growth factor (HGF) is a mesenchyme‐derived pleiotropic factor, and angiogenesis is included in a variety of its functional effects. HGF levels were measured in 5 sessions of low‐density lipoprotein (LDL) apheresis in 3 patients with severe hypercholesterolemia. Blood was collected at the start (T0) and at 1,000 ml (T1), 2,000 ml (T2), and 3,000 ml (T3) plasma treatments. During LDL apheresis, HGF levels increased from 1.59 ± 0.78 (mean ± SE, n = 5) ng/ml at T0 to 6.64 ± 0.97 at T1, 6.28 ± 0.97 at T2, and 5.20 ± 0.94 at T3. In one apheresis session, HGF increased immediately at the 100 ml plasma treatment stage. HGF was adsorbed completely by a dextran‐sulfate (DS) column. Despite the adsorption by the DS column, HGF in the patient blood increased to the levels with functional effects. The improvement of ischemic symptoms due to LDL apheresis may be related to the angiogenic activities of HGF.

LDL-apheresis improves peripheral arterial occlusive disease with an implication for anti-inflammatory effects

“…However, the underlying mechanism(s) still remains unknown. Of the findings so far reported [11][12][13][14][15][16], intriguing possibilities are those related with neovascularization or increased blood flow. Recently, we added important evidence that serum levels of VEGF and IGF-I may contribute to the favorable effects for ischemic limbs [20].…”

“…Particularly, with respect to the favorable effects of LDL-apheresis for the treatment of PAOD, it is clear that the reduction of high levels of plasma LDL does not contribute to the improvement of limb ischemia [10]. So far, regarding the mechanisms by which LDL-apheresis improves limb ischemia seen in patients with PAOD, it has been shown that a reduction of blood viscosity [11], an improvement in erythrocyte deformation [12], increased production of nitric oxide and bradykinin [13], a reduction of adhesion molecules on mononuclear cells [14], an improvement of endotheliumdependent vasodilatation [15], and an increase in hepatocyte growth factor (HGF) [16] may be involved. VEGF (vascular endothelial growth factor) is known to play an important role for angiogenesis [17].…”

Applications of LDL-apheresis in nephrology

“…Particularly with respect to the favorable effects of LA in the treatment of PAD, it is clear that the reduction of high levels of plasma LDL does not contribute to the improvement of limb ischemia [15]. As for the mechanisms accounting for improvement of limb ischemia seen in patients with PAD, it has been shown that a reduction of blood viscosity [16], an improvement in erythrocyte deformation [17], increased production of nitric oxide and bradykinin [18], a reduction of adhesion molecules on mononuclear cells [19], an improvement of endotheliumdependent vasodilatation [20], a decrease in plasma matrix metalloproteinase-9 (MMP-9) and serum tissue inhibitor of matrix mettalloproteinase-1 (TIMP-1) [21], and an increase in hepatocyte growth factor (HGF) [22] may be involved ( Table 1).…”

Efficacy of low‐density lipoprotein apheresis in arteriosclerosis obliterans of the lower extremities: Two cases with marked alleviation of clinical symptoms

“…Mii This finding appeared to reflect effects of LDL-A other than those on lipids. This view has been supported by reports that in addition to effects on lipids, LDL-A has diverse other effects, including improvement of blood rheology [8,9], improvement in erythrocyte deformation [10], reduction of fibrinogen [11], increased production of nitric oxide and bradykinin [12], reduction of oxidative stress through effects on vascular endothelial function [13], reduction of adhesion molecules [14], and effects on vascularization factors [6,15].…”