Recombinant apolipoprotein A-I(Milano) infusion into rabbit carotid artery rapidly removes lipid from fatty streaks.

Apolipoprotein A-I(Milano) (AIM), a natural variant of human apolipoprotein A-I, confers to carriers a significant protection against vascular disease. In previous studies, administration of recombinant AIM-phospholipid (AIM-PL) complexes to hypercholesterolemic rabbits markedly inhibited neointimal formation after arterial injury; moreover, repeated injections of AIM-PL in apoE-deficient mice significantly reduced atherosclerosis progression. The objective of the present study was to determine if a single localized infusion of AIM-PL complexes administered directly to atheromatous lesions could promote plaque regression. Lipid-rich, atheromatous plaques were generated at both common carotid arteries of 25 rabbits by applying a perivascular electric injury, followed by 1.5% cholesterol diet for 90 days. Rabbits were infused with either saline, phospholipid vesicles, or 3 different AIM-PL doses (250, 500, or 1000 mg of protein) delivered through an intravascular ultrasound (IVUS) catheter positioned at the origin of the right carotid. The lesions at the left carotid artery were therefore exposed to the agents systemically. Infusion of AIM-PL at the 2 highest doses caused reduction of right carotid artery plaque area by the end a 90-minute infusion as assessed by IVUS analysis. Plaque area regression was confirmed by histology in carotid arteries receiving direct (500 and 1000 mg doses) and systemic (500 mg dose) delivery, 72 hours after the start of the treatment. Plaque lipid content was associated with significant and similar decreases in Oil Red O staining in both arteries. These results suggest AIM-PL complexes enhanced lipid removal from arteries is the mechanism responsible for the observed plaque changes.

Soy proteins reduce progression of a focal lesion and lipoprotein oxidiability in rabbits fed a cholesterol-rich diet.

The effects of different dietary proteins on the progression of a focal atheromatous lesion and on lipoprotein oxidiability were studied in male New Zealand rabbits. Focal lesions were induced on common carotid arteries by applying an electric current, using a bipolar microcoagulator. After surgery, animals were fed for 90 days two different diets, both with 1% cholesterol, 15% saturated fatty acids and 20% protein: the protein source was constituted in one group (SOY) by 16% soy protein isolate plus 4% milk whey proteins, in the other (CASEIN) by 16% casein plus 4% milk whey proteins. Lower levels of plasma cholesterol and triglycerides (-47 and -65%, respectively) (P < 0.05) were detected in the SOY versus the CASEIN group at the end of treatment. Cryosection analyses of the carotids, indicated a highly significant reduction (-39%; P < 0.05) in the focal lesion progression in the SOY versus the CASEIN group. Copper-mediated oxidation of low-density lipoprotein (LDL) from rabbits fed the two different diets, performed in vitro by analysis of conjugated diene formation, showed a significantly longer lag phase in the SOY (150 +/- 5 min) versus the CASEIN animals (20 +/- 3 min) (P < 0.05). These data, while confirming the well-known lipid lowering properties of soy proteins, indicate, in this animal model, a remarkable activity on a focal atheromatous lesion, possibly also linked to a powerful antioxidant activity.