Prelesional modifications of the vessel wall in hyperlipidemic atherogenesis. Extracellular accumulation of modified and reassembled lipoproteins.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
D A Filip
Publications and source records attributed to D A Filip.
The hyperlipidemic hamster as a model of experimental atherosclerosis.
Male hamsters were fed a hyperlipidemic diet consisting of standard chow supplemented with 3% cholesterol and 15% commercial butter for 12 months. In about 3 weeks serum total cholesterol doubled, raised 4-fold after the 4th week and after 10 months attained a 17-fold value. Low density lipoproteins (LDL)-cholesterol increased 4-fold after 4 weeks and about 13-fold after 10 months compared to control animals. In the first 2 weeks mononuclear cells began to adhere to the endothelium and a very intense stromal reaction appeared in the intima of the aortic arch. At the end of the 4th week of diet, Oil Red O stainable deposits were visible on the thoracic aorta, mostly on the arch, some of them as isolated, lipid-laden cells and others distributed on focal areas. Smooth muscle cells (SMC) appeared also in the intima of hyperlipidemic hamsters, compared to normal animals which had no macrophages or smooth muscle cells in the intima of the aortic specimens examined. Up to 6 months, smooth muscle cells in the intima and media began to load with lipids, as well as endothelial cells. After 10 months the affected zones looked like human atherosclerotic plaque with huge cholesterol crystal deposits, calcium deposits and necrosis. The endothelium, though very thinned and loaded with lipids, was morphologically intact.
Animals↗
Cellular events in the development of valvular atherosclerotic lesions induced by experimental hypercholesterolemia.
The onset and evolution of ultrastructural changes in the cardiac valves induced by a cholesterol-rich diet were investigated in rabbit and hamster. In both animal models, the atrioventricular and sigmoid valves were comparably affected by lesions intermediary between fatty streak and fibrous plaque. The earliest detectable modification was the progressive accumulation in the subendothelium of extracellular liposome-like structures rich in unesterified cholesterol, associated with the proliferation of a basal lamina-like material. This was followed by the diapedesis of blood monocytes in the same location, which became macrophages increasingly loaded with lipid deposits. Resident interstitial cells accumulate lipids, as well. In advanced stages, the macrophage-derived foam cells clustered, deforming the valve leaflets. The resident macrophages accumulated lipids later and more slowly, while partly preserving their ultrastructure. The advanced lesions are characterized by marked stromal proliferation, massive intra- and extracellular deposition of lipids and cholesterol crystals and the appearance of a necrotic core. The salient findings of these studies were: (1) the appearance of extracellular liposomes as the earliest event in atherogenesis; (2) the capability of the valvular interstitial cells to accumulate lipids; and (3) the slow response of resident macrophages to the cholesterol-rich diet. The results revealed that hypercholesterolemia produces in the cardiac valves atherosclerotic lesions of an intermediate type, which can deform the leaflets thus altering their normal function.
Animals↗
Interstitial cells of the heart valves possess characteristics similar to smooth muscle cells.
Interstitial cells of heart atrioventricular and sigmoid valves were examined in several laboratory animals (rabbit, hamster, rat, and mouse) and in humans. These cells constitute a large fraction of the total cell population of the valve; in mouse atrioventricular valves, they amount to approximately 30% of the volumetric density. By their ultrastructural features and functional properties, valvular interstitial cells are intermediate between fibroblasts and vascular smooth muscle cells. Like fibroblasts, valvular interstitial cells lack a basal lamina establishing direct and extensive contacts with collagen fibers, elastin microfibrils, and proteoglycans of the matrix. The cells have numerous slender and long processes, connected to one another, forming a complex cellular framework spanning the entire valve. Similar to smooth muscle cells, valvular interstitial cells are extensively coupled by communicating junctions as shown by thin sections, freeze-fracture, lanthanum staining, and carboxyfluorescein microinjection. The cells contain numerous bundles of actin filaments, which are decorated by the S1 fragment of heavy meromyosin. Valvular interstitial cells also express cyclic guanosine-monophosphate-dependent protein kinase, as detected by immunofluorescence and immunoperoxidase histochemistry. Motor nerve endings are located closely apposed to valvular interstitial cells: structurally most of them appear to be of the adrenergic type. Valvular interstitial cells contract on epinephrine or angiotensin II stimulation as shown both in culture and in situ (valvular strips). Taken together these observations suggest that VIC may have contractile properties, which can account for a controlled tonus, actively correlated with the cyclically changing forces acting on valves during diastole and systole.
Actin Cytoskeleton↗
The metaphase chromosome ultrastructure. II. Helical organization of the basic chromosome fiber as revealed by acute angle metal deposition.
The acute angle metal depositon technique, discloses a helical chromosome fiber substructure. The microdensitometric analysis of the fiber parameters shows that a fibril 152 A in diameter coils to form the basic chromosome fiber 295 A in diameter with a pitch of 247 A. These figures should be corrected because of the thickening due to metal deposition, the real dimensions would be closer to 112 A for the fibril diameter and 255 A for fiber diameter. The real pitch value is probably somewhat smaller than 247 A (approximatively 200 A) as the values were obtained by analysing slightly stretched fibers. These results support the helical model of the chromosomes fiber organization and show that, most probably, the metaphase chromosome fiber as seen in electron microscopy is the second order of helical packing.
Chromium↗
The metaphase chromosome ultrastructure. I. Acute angle metal deposition technique as an appropriate use of shadow casting in chromosome structure investigation.
Explore the source record for details and available documents.
Chromium↗
The Ranvier node as a chemo-electric pulsatory unit: a study of its structure-functions relations.
The Ranvier node of (Rana temporaria) frog nerve fibres is investigated by electron microscopy, Particular attention is given to the paranodal septate structures and to the extranodal junction of two Schwann cells. An interpretation of the functional meaning of these structures along with a quantitative analysis of the Schwann extranodal junction as regards the diffusion from/to the node is attempted. A 73 per cent reduction of the diffusion coefficient is obtained if the extranodal Schwann cell processes are considered impermeable to the diffusing vectors which indicates a protective role. Only 1 per cent reduction is obtained in the case of excitation-involved cations to which the Schwann cell membrane is considered to be permeable. This indicates the active role of the Schwann cell in the extranodal area ion diffusion, by minimizing the variations in ion concentration near the nodal membrane. Thus the nervous fibre-Schwann cell assembly may be regarded as a balanced pulsatory chemo-electric unit.
Animals↗
Mouse atrio-ventricular valve ultrastructure morphometrical correlations.
Morphometric data on mouse atrio-ventricular valve ultrastructure are reported. The statistical analysis of the volumetric density percentage for cellular and extracellular valve components and of endothelial plasmalemmal vesicle density for the different endocardial domains (atrial, valvular and ventricular) showed: the bicuspid compared to the tricuspid valve has a more important lymphatic drainage, less vascularization, higher endothelial plasmalemmal vesicle density and more macrophages, striated muscle cells and collagen along with fewer interstitial cells, nervous terminals and elastin in the leaflet; the valvular endothelium as compared to other endocardial domains has a higher density of plasmalemmal vesicles, considering the results for both endothelial fronts (luminal and abluminal).
Animals↗