Triglyceride-rich lipoproteins isolated by selected-affinity anti-apolipoprotein B immunosorption from human atherosclerotic plaque.

We isolated and characterized immunoreactive apolipoprotein B (apoB)-containing lipoproteins from human atherosclerotic plaque and plasma to determine whether very-low-density lipoprotein (VLDL) can enter and become incorporated into the atherosclerotic lesion and how plaque apoB-containing lipoproteins differ from apoB-containing lipoproteins isolated from plasma. Atherosclerotic plaques were obtained during aortic surgery and processed immediately. Lipoproteins were extracted from minced plaque in a buffered saline solution (extract A). In selected cases a second extraction was done after plaque was incubated with collagenase (extract B). Lipoproteins were then isolated from the extracts by anti-apoB immunosorption and separated into VLDL + intermediate-density lipoprotein (IDL) (d < 1.019 g/mL) and low-density lipoprotein (LDL) (1.019 < d < 1.070 g/mL) fractions by ultracentrifugation. The VLDL + IDL fractions from plaque contained more than one third of the total apoB-associated lipoprotein cholesterol in both extracts A and B. The lipid composition of VLDL + IDL in both extracts was related to that of plasma VLDL + IDL. By electron microscopy mean particle diameters of VLDL + IDL from extracts A and B were 9% and 23%, respectively, greater than VLDL + IDL diameters from plasma. Mean diameters of LDL from extracts A and B were 11% and 31% greater than LDL diameters from plasma. The apoE-apoB ratio of extract A VLDL + IDL was nearly twice that of plasma VLDL + IDL and severalfold higher than that of extract A LDL. Immunoblots of both VLDL + IDL and LDL from extract A demonstrated minimal fragmentation of apoB.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of injury induced intimal hyperplasia by saralasin in rats.

Increasing evidence points toward local production of renin and angiotensinogen in the artery wall. Because angiotensin converting enzyme (ACE) inhibitors have been shown to block intimal hyperplasia after arterial injury in the rat, it has been suggested that angiotensin II is an important mediator of the proliferative response to vascular injury. To prove that previous observations with use of ACE inhibitors are a result of effects on local angiotensin levels versus nonspecific drug effects, we tested the ability of an unrelated drug, the angiotensin II receptor antagonist saralasin, to similarly block intimal hyperplasia after aortic injury in the rat. Balloon catheter aortic denudation was performed in 28 rats pharmacologically treated for 14 days after surgery and split into four groups: group 1, saralasin 360 micrograms/kg/hr intravenously; group two, normal saline 0.5 mm3/hr intravenously; group 3, captopril 100 mg/kg/day orally; and group 4, heparin 50 U/kg/hr intravenously. Animals were killed and aortas were perfusion fixed at physiologic pressure 14 days after denudation. Cross-sectional intima-to-media ratios were calculated by computerized planimetry. Compared with saline controls, saralasin inhibited intimal hyperplasia 45% (p less than 0.001), captopril 59% (p less than 0.001), and heparin 68% (p less than 0.001). A reduction in total intimal area was also evident in animals treated with saralasin (p less than 0.01). Blood pressure in the group treated with captopril decreased from 107.4 +/- 3.9 to 96.3 +/- 4.3 mm Hg (p less than 0.01) after 6 days, whereas saralasin and heparin had no effect on blood pressure. Weight gain during the study was reduced in groups treated with captopril and heparin but not in the group treated with saralasin.(ABSTRACT TRUNCATED AT 250 WORDS)

Relation of plasma lipid and apoprotein levels to progressive intimal hyperplasia after arterial endarterectomy.

BACKGROUND: To examine the relation of plasma lipoproteins to the proliferative response after arterial injury in humans, we examined the plasma lipid, lipoprotein, and apoprotein levels of 20 patients with early recurrent stenosis caused by intimal hyperplasia after carotid endarterectomy. These were compared with 20 controls who had no evidence of recurrent stenosis by duplex ultrasound scanning. METHODS AND RESULTS: By univariate analysis, the reoperated patients had higher levels of plasma cholesterol (251 versus 225 mg/dl, p less than 0.05), total triglycerides (173 versus 105 mg/dl, p less than 0.03), and low density lipoprotein (LDL) apoprotein B (99.8 versus 77.2 mg/dl, p less than 0.003). The ratio of cholesterol to apoprotein B in LDL was lower in patients with restenosis (p less than 0.04), suggesting LDL of smaller diameter. High density lipoprotein (HDL) cholesterol level was reduced (45 versus 55 mg/dl, p less than 0.01) in patients with restenosis. With statistical adjustment for the correlations between these variables by multivariate analysis, both LDL apoprotein B and HDL cholesterol were independent predictors of the risk of restenosis. Ten patients with restenosis but only two controls had one or two apolipoprotein E4 alleles. CONCLUSIONS: Elevated lipid levels usually associated with an increased risk of atherosclerosis may predispose patients to an increased incidence of intimal hyperplasia after endarterectomy.