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D J Falcone

Publications and source records attributed to D J Falcone.

46 records · Page 3Linked to original sources
PubMed1984

Lipoprotein and albumin accumulation in reendothelialized and deendothelialized aorta.

Although arterial injury is believed to be an important factor in the pathogenesis of atherosclerosis, little is known about lipoprotein accumulation in the injured arterial wall. In experiments reported here, the authors quantitated the accumulation of iodinated lipoprotein and albumin in reendothelialized and deendothelialized rabbit aorta. Results indicate that over the experimental period, insudated lipoprotein but not albumin is retained in the reendothelialized aorta. Neither lipoprotein nor albumin was retained in the adjacent persistently deendothelialized aorta. Findings are consistent with the hypothesis that sequestration of lipoprotein in reendothelialized artery is one mechanism by which lipid accumulates in these areas.

Animals↗
PubMed1982

Prostacyclin modulates cholesteryl ester hydrolytic activity by its effect on cyclic adenosine monophosphate in rabbit aortic smooth muscle cells.

We tested the hypothesis that prostacyclin (PGI2), 6-keto-prostaglandinF1 alpha(6-keto-PGF1 alpha), and several E series prostaglandins (PG) may affect the activity of cholesteryl ester (CE) hydrolase since our previous experiments indicated that smooth muscle cells (SMC) in neointima of injured rabbit aorta (a) acquire the capacity to produce PGI2 and (b) have increased lysosomal CE hydrolytic (acid cholesteryl ester hydrolase [ACEH])activity. Using cultured SMC from rabbit thoracic aorta, we demonstrated that PGI2, 6-keto-PGF1 alpha, and 6-keto-PGE1 enhanced ACEH activity fourfold. No significant effects on ACEH activity were observed with PGE1 or PGE2. Preincubation of SMC with an inhibitor of adenylate cyclase activity (dideoxyadenosine) abolished the effect of these PG on CE hydrolytic activity. Addition of dibutyryl cAMP to these SMC significantly increased ACEH activity. Although concentrations of PGI2 used significantly increased cAMP levels, proliferation of these SMC was not observed. In related experiments, we determined if the addition of PGI2, 6-keto-PGF1 alpha, or 6-keto-PGE1 to cultured aortic SMC would enhance the egress of unesterified cholesterol and CE from these SMC. A significant loss of total cholesterol from PG-treated SMC was observed at the end of 14 d. Results suggest that increased synthesis of PGI2 by neointimal SMC in the injured aortic wall may, at least in part, explain the changes in CE catabolism and accumulation following injury. These PG may also be important in CE metabolism and accumulation in human arteries.

Animals↗
PubMed1982

Diet-induced hypercholesterolemia inhibits the recovery of prostacyclin production by injured rabbit aorta.

The effect of diet-induced hypercholesterolemia on the recovery of prostacyclin (PGI2) synthetic capacity was assessed at the luminal surface of previously injured rabbit aorta. Prostacyclin synthesis and release were measured by radioimmunoassay following arachidonic acid stimulation of deendothelialized and reendothelialized aortas of hypercholesterolemic rabbits. Assay of PGI2 production by aorta was performed at 15, 35, and 70 days following removal of endothelium with a balloon catheter. Prostacyclin production by both deendothelialized and reendothelialized areas of aorta from normocholesterolemic rabbits was initially low following injury and increased with time, reaching levels at 70 days equal to uninjured aortas. Prostacyclin production by both deendothelialized and reendothelialized areas of aorta from rabbits with moderately elevated serum cholesterol concentrations (203 to 350 mg/dl) was also initially low, but in contrast to normocholesterolemic rabbits, it did not increase with time. Results indicate that hypercholesterolemia like that seen in humans inhibits the recovery of PGI2 production in deendothelialized and reendothelialized areas of previously injured rabbit aorta.

Animals↗
PubMed1981

Recovery of prostacyclin production by de-endothelialized rabbit aorta. Critical role of neointimal smooth muscle cells.

Prostacyclin (PGI2) synthetic capacity was assayed at the surface of aortas at various intervals after removal of endothelium with a balloon catheter. Results were correlated with morphologic changes in the vessel wall seen by light microscopy, scanning and transmission electron microscopy. To assay PGI2 synthetic capacity, we applied an incubation chamber to the luminal surface of the aortas; after arachidonic acid stimulation we assayed the PGI2 synthesized with a bioassay and radioimmunoassay. PGI2 synthesis in de-endothelialized aortas was determined immediately after balloon-catheter injury and at intervals of 1 h and 2, 4, 15, 35, and 70 d. PGI2 synthesis was low at 1 h and increased over time with levels at 35 and 70 d reaching that of normal artery. Scanning and transmission electron microscopy of de-endothelialized areas showed persistent absence of endothelium with formation of a neointima composed of smooth muscle cells. De-endothelialized aorta was covered with adherent platelets shortly after injury, however several days later only a few platelets adhered to the denuded surface. Results indicated that (a) endothelium is responsible for nearly all PGI2 production at the luminal surface of the normal aorta, (b) de-endothelialized muscular neointima synthesized increasing quantities of PGI2 with time after injury, and (c) increase of PGI2 production at the luminal surface of de-endothelialized aorta correlates with formation of a neointima and with the acquired thromboresistance of the aorta.

Animals↗
PubMed1981

Endothelium modifies the altered metabolism of the injured aortic wall.

Results of previous experiments in this laboratory indicate that lipids, especially cholesterol and cholesteryl ester, preferentially accumulate in re-endothelialized, as compared with de-endothelialized, areas of aorta (Am J Pathol 1980, 99:81-104). In the experiments reported here, the hypothesis that this lipid accumulation results from alterations in arterial wall metabolism induced by injury and modified by endothelium was tested. Activities of the two cholesterol-ester-metabolizing enzymes acyl CoA: cholesterol acyltransferase and acid cholesteryl esterase were assayed in uninjured aortas and in de-endothelialized and re-endothelialized areas of balloon-catheter-injured aortas from normocholesterolemic and hypercholesterolemic rabbits. Activities of marker enzymes for major cell organelles were also assayed. Our results indicate that acyl CoA: cholesterol acyltransferase activity was similarly increased in re-endothelialized and de-endothelialized areas of injured aortas. Activity of acid cholesteryl esterase was also increased; however, it was significantly less in re-endothelialized as compared with de-endothelialized areas. Activities of several marker enzymes were changed in injured aortas, particularly in de-endothelialized as compared with re-endothelialized areas. These findings suggest that 1) injury predisposes to general metabolic changes in the aorta that are modified by endothelium and 2) increased cholesteryl ester accumulation in re-endothelialized aortas occurs at least in part from increased synthesis and decreased hydrolysis.

Animals↗
PubMed1980

Enhancement of cholesterol and cholesteryl ester accumulation in re-endothelialized aorta.

The purpose of the experiments reported here was to determine chemically the character and quantity of lipid in re-endothelialized and de-endothelialized areas of rabbit aortas. The aortas of 22 rabbits, Groups I and II, were de-endothelialized with a balloon catheter, and the rabbits were maintained on a lipid-poor diet for 4 weeks. Thirteen rabbits, Group II, were then fed an egg-supplemented diet for 6 weeks. Nine rabbits, Group I, were continued on the lipid-poor diet for an additional 6 weeks. Control rabbits with uninjured aortas were fed a lipid-poor diet for 10 weeks (Group III) or an egg-supplemented diet for 6 weeks (Group IV). Nonesterified cholesterol and fatty acids, cholesteryl esters, triacylglycerols, and squalene were quantitated in re-endothelialized and de-endothelialized aorta by thin-layer chromatography and fluorometric analysis. The results indicate 1) that there was approximately three times as much nonesterified cholesterol and cholesteryl ester in re-endothelialized aorta of Groups I and II as compared with adjacent de-endothelialized aorta and 2) that in re-endothelialized aorta of Group II the amount of total cholesterol correlated with serum cholesterol concentration in contrast to adjacent de-endothelialized aorta, with no correlation over a range of nearly 900 mg/100 ml. These studies indicate that the presence of endothelium favors accumulation of aortic cholesteryl esters. The results suggest that arterial lipid accumulation is not simply a result of passive filtration but may result from metabolic differences in the re-endothelialized neointima.

Animals↗
PubMed1976

The challenge of comparative health policy for political science.

After a brief review of the literature and some reflection on the state of the art, this paper argues that more analyses of health policy in an explicitly comparative perspective are needed. This conclusion is based on a discussion of the largely unexploited benefits that could accrue from a welding of political science and health services research and a consideration of a research design illustrating the compatibility of these two endeavors.

Delivery of Health Care↗
PubMedDate not supplied

Fibronectin stimulates macrophage uptake of low density lipoprotein-heparin-collagen complexes.

In this study, we investigated whether fibronectin will enhance macrophage uptake of particulate complexes of low density lipoproteins (LDL), heparin, and fibrillar collagen and whether fibronectin's opsonic effect could be modulated by the heparin component in these model matrices. We isolated a heparin fraction (HepFn) based on its affinity to fibronectin. HepFn appeared more charged than unfractionated heparin, as evidenced by enhanced electrophoretic mobility and ability to effect a cathodic shift in the electrophoretic migration of fibronectin. HepFn lacked the smaller molecular weight species present in unfractionated heparin. Macrophage endocytosis of LDL-heparin-collagen complexes, as evidenced by the intracellular accumulation of LDL-derived cholesteryl esters and endogenously synthesized cholesteryl esters, was enhanced by fibronectin. When LDL matrix complexes were prepared with HepFn, fibronectin's opsonic properties were significantly enhanced. F(ab)2 fragments of anti-fibronectin, capable of inhibiting fibronectin's opsonization of gelatin-derivatized latex particles, inhibited the fibronectin-dependent stimulation of cholesteryl ester synthesis by macrophages exposed to LDL-HepFn-collagen complexes. Thus, fibronectin stimulates macrophage endocytosis of LDL matrix complexes. The affinity of the constituent glycosaminoglycan for fibronectin is important in the regulation of this phenomenon.

Animals↗