Infusion of Reconstituted High-Density Lipoprotein Leads to Acute Changes in Human Atherosclerotic Plaque

TLDR

Prior studies have shown that multiple infusions of reconstituted HDL reduce plaque volume and alter ultrasound characteristics. This study aimed to determine whether a single rHDL infusion can acutely modify plaque characteristics in humans. Twenty claudicants undergoing superficial femoral artery revascularization were randomized to receive a 4‑hour infusion of 80 mg/kg rHDL or placebo, and 5–7 days later plaque was excised by atherectomy for analysis. rHDL infusion significantly lowered VCAM‑1 expression and plaque lipid content, increased HDL‑cholesterol and cholesterol‑efflux capacity, and reduced macrophage size and inflammation, suggesting a potential cardioprotective effect.

Abstract

Studies have shown a reduction in plaque volume and change in plaque ultrasound characteristics after 4 infusions of reconstituted high-density lipoprotein (rHDL). Whether rHDL infusion leads to acute changes in plaque characteristics in humans is not known. Patients with claudication scheduled for percutaneous superficial femoral artery revascularization were randomized to receive 1 intravenous infusion of either placebo or rHDL (80 mg/kg given over 4 hours). Five to 7 days following the infusion, patients returned and revascularization was performed including atherectomy to excise plaque from the superficial femoral artery. Twenty patients (17 males) average age, 68±10 years (mean±SD) were recruited. Eleven patients had a history of documented coronary artery disease, all patients were on aspirin, and 18 were on statins. Ten of the patients received rHDL and 10 placebo. There was significantly less vascular cell adhesion molecule-1 expression (28±3% versus 50±3%; P <0.05) and a reduction in lipid content in the plaque of HDL-treated subjects compared to placebo. The level of HDL cholesterol increased by 20% after infusion of rHDL and the capacity of apolipoprotein B–depleted plasma to support cholesterol efflux increased. Intravenous infusion of a single dose of reconstituted HDL led to acute changes in plaque characteristics with a reduction in lipid content, macrophage size, and measures of inflammation. These changes may contribute to the cardioprotective effects of HDL.