Background—
Atherosclerosis is complicated by cardiovascular events such as myocardial infarction, stroke, or peripheral arterial occlusive disease. Inflammation and pathological neovascularization are thought to precipitate plaque rupture or erosion, both causes of arterial thrombosis and cardiovascular events. We tested the hypothesis that arterial inflammation and angiogenic events are increased throughout the arterial tree in vulnerable patients, ie, in patients who suffered from cardiovascular events, compared with patients who never suffered from complications of atherosclerosis.
Methods and Results—
In a postmortem study, we quantified the inflammatory infiltrate and microvascular network in the arterial wall of iliac, carotid, and renal arteries. Tissue microarray technology was adapted to investigate full-thickness arterial sectors. We compared 22 patients with symptomatic atherosclerosis with 27 patients who never had suffered from any cardiovascular event. The absolute intimal macrophage content was 2- to 4-fold higher in vulnerable patients at all 3 arterial sites analyzed (
P
<0.05). Patients with symptomatic atherosclerosis had a denser network of vasa vasorum than patients with asymptomatic disease (33±2 versus 25±2 adventitial microvessels per 1 mm
2
;
P
=0.008). Hyperplasia of vasa vasorum was an early and macrophage infiltration was a late sign of symptomatic atherosclerosis.
Conclusions—
High intimal macrophage content and a hyperplastic network of vasa vasorum characterize vulnerable patients suffering from symptomatic atherosclerosis. These changes are uniformly present in different arterial beds and support the concept of symptomatic atherosclerosis as a panarterial disease.
To optimize the preparation of immunoliposomes, we investigated the coupling of thiolated IgG and BSA to liposomes using a novel group of coupling lipids. All lipids consist of cholesterol as membrane anchor and a thiol-reactive maleimide headgroup, linked by a spacer that differs in length and polarity (ethylene glycol, tetraethylene glycol, PEG 400, PEG 1000, dodecyl). In addition, lipids differ in the electrophilicity of the maleimide group (p- or m-maleimidobenzoic ester). In the case of BSA, coupling efficiency strongly depended on the electrophilicity of the maleimide group as well as on the spacer polarity: The less electrophilic meta constitution seems to be an advantage over the p-maleimidobenzoic ester, resulting in higher coupling efficiency. Polar spacers (tetraethylene glycol, 46%) achieved a higher coupling efficiency than a nonpolar spacer with approximately the same length (dodecyl, 15%).When liposomes containing coupling lipids with the spacers tetraethylene glycol, PEG 400, and PEG 1000 were linked to BSA, coupling efficiencies were in a medium range and similar (41-46%) but were lower for the short ethylene glycol spacer (30%). In contrast, for IgG coupling efficiencies correlated with increasing spacer length. Best results were obtained using coupling lipids with a long polar spacer (PEG 1000) (65%), whereas a coupling lipid bearing a short spacer (ethylene glycol) resulted in a low coupling efficiency of 12%.
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