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W Hollander

Publications and source records attributed to W Hollander.

52 records · Page 3Linked to original sources

The protein and lipid composition of arterial elastin and its relationship to lipid accumulation in the atherosclerotic plaque.

Elastin preparations from intimal layers and the media of normal and atherosclerotic human aortae were analyzed for protein and lipid content. In atherosclerotic aortae, elastin from plaques was compared with elastin from adjacent normal appearing areas of the same aorta. Arterial elastin purified by alkaline extraction appeared to be a protein-lipid complex containing free and ester cholesterol, phospholipids, and triglycerides. The lipid component of normal arterial elastin was small (1-2%). With increasing severity of atherosclerosis, there was a progressive accumulation of lipid in intimal elastin from plaques, reaching a mean lipid content of 37% in severe plaques. The increase in the lipid content of plaque elastic preparations was mainly due to large increases in cholesterol, over 80% of which was cholesteryl ester. This deposition of cholesterol in plaque elastin accounted for 20-34% of the total cholesterol content of the plaque. The increased lipid deposition in plaque elastin was associated with alterations in the amino acid composition of plaque elastin. In elastin from plaque intima, the following polar amino acids were increased significantly: aspartic acid, threonine, serine, glutamic acid, lysine, histidine, and arginine; whereas, cross-linking amino acids: desmosine, isodesmosine, and lysinonorleucine were decreased significantly. The amino acid and lipid composition of elastin from normal appearing aortic areas was comparable to that of normal arterial elastin except for intimal elastin directly adjacent to and medial elastin directly below the most severe plaques.The data indicate that the focal lipid deposition in early atherosclerotic plaques is due to a large extent to lipid accumulations in altered elastin protein of localized intimal areas. Continued lipid deposition in altered elastin appears to contribute substantially to the progressive lipid accumulation in the plaque. The study suggests that elastin of intimal elastic membranes may play an important role in the pathogenesis and progression of atherosclerosis.

Adolescent↗

Arterial wall metabolism in experimental hypertension of coarctation of the aorta of short duration.

Coarctation of the mid-thoracic aorata was surgically produced in mongrel dogs which were sacrificed from 4-12 wk after the operation. As compared to the findings in control animals, the sodium, chloride, and water content of the hypetensive portion of the coarcted thoracic aorta was significantly elevated, whereas the electrolyte and water content of the relatively normotensive portion of the coarcted aorta was normal. The sodium, potassium, and water content of the pulmonary artery, skeletal muscle, and cardiac muscle of the coarcted dog was not altered. These observations suggest that an elevated arterial pressure may influence the electrolyte and water composition of the arteries. The arterial pressure also may influence the content and synthesis of acid mucopolysaccharides (MPS) in the arteries since the content of sulfated MPS and the incorporation of injected radiosulfate into sulfated MPS were significantly increased in the hypertensive portion of the coarcted thoracic aorta but were significantly reduced in the relatively normotensive ("hypotensive") portion of the coarcted aorta. The observed increase in MPS may have been a factor directly responsible for the increase in the sodium content of the hypertensive aorta since MPS can act as polyelectrolytes and bind cations. Although the arterial pressure may influence certain metabolic functions in the arteries, it did not appear to have a direct effect on the arterial lipids since the lipid content of the hypertensive and of the relatively normotensive portions of the coarcted aorta were comparable to the values found in the normal aorta.

Animals↗

Increased microglial activation and protein nitration in white matter of the aging monkey.

Activated microglia are important pathological features of a variety of neurological diseases, including the normal aging process of the brain. Here, we quantified the level of microglial activation in the aging rhesus monkey using antibodies to HLA-DR and inducible nitric oxide synthase (iNOS). We observed that 3 out of 5 white matter areas but only 1 of 4 cortical gray matter regions examined showed significant increases in two measures of activated microglia with age, indicating that diffuse white matter microglial activation without significant gray matter involvement occurs with age. Substantial levels of iNOS and 3-nitrotyrosine, a marker for peroxynitrite, increased diffusely throughout subcortical white matter with age, suggesting a potential role of nitric oxide in age-related white matter injury. In addition, we found that the density of activated microglia in the subcortical white matter of the cingulate gyrus and the corpus callosum was significantly elevated with cognitive impairment in elderly monkeys. This study suggests that microglial activation increases in white matter with age and that these increases may reflect the role of activated microglia in the general pathogenesis of normal brain aging.

Aging↗

Radiologic evaluation of cerebrovascular disease in experimental atherosclerosis in a subhuman primate model.

In a series of animal experiments to provoke atherosclerosis, angiographic evaluation of the cerebral vessels was obtained. The angiographic evaluation of cerebral changes and correlation with the pathological alterations known to occur illustrate the value of this technique in long term analysis of induced atherosclerosis in the experimental animal. Control groups, high cholesterol diet groups, and induced hypertensive groups with and without a high cholesterol diet were evaluated by serial angiographic techniques. Examples of angiographic changes are demonstrated and have proven of considerable value in following the progress of the vascular changes.

Animals↗

Changes in aortic lysyl oxidase activity in diet-induced atherosclerosis in the rabbit.

This study assessed the responses of lysyl oxidase, the enzyme that initiates covalent crosslinking in elastic and collagen, by studying the aortic tissue of rabbits after arteriosclerosis had been induced by diet. Rabbits in the experimental group were fed an atherogenic diet of rabbit chow supplemented with 8% peanut oil and 2% cholesterol for varying periods of time, while the control group was fed only rabbit chow. Lysyl oxidase activity was found to be distributed throughout the length of the thoracic and abdominal aortas of the normal rabbits, However, rabbits fed the atherogenic diet showed marked increases in enzyme in the aortic arch, a change that was initially evident after 30 days and became greatest (2.5 times that of the controls) after 90 days. Enzyme activity in the study rabbits increased only minimally in the abdominal aortic wall. Aortic prolyl hydroxylase activity measured after 60 days of feeding changed in degree and manner similar to lysyl oxidase activity. These region-specific changes in enzyme activities correlated with the distribution and severity of aortic lesions in this model of the disease. Lysyl oxidase activity increased dramatically in this model of atherosclerosis, suggesting that this extracellular enzyme activity may prove to be a vulnerable and accessible point of control of the fibrotic response in atherosclerosis.

Amino Acid Oxidoreductases↗

Arterial hypertension injures brain capillaries. Definition of the lesions. Possible pathogenesis.

Systemic hypertension (secondary to aortic coarctation) produces in monkeys, multifocal brain lesions where capillaries show increased diameter, endothelial degeneration and deposition of collagen and other substances in the basement membrane. In one animal, capillary changes were detected as early as 8 weeks after induction of hypertension. Similar capillary alterations were demonstrated in brain samples of hypertensive humans obtained at autopsy. We suggest that the above abnormalities may be the result of successive episodes of regional ischemia and/or hyperperfusion. Validation of these observations requires careful evaluation of additional human and animal brains.

Animals↗

Innervation of brain intraparenchymal vessels in subhuman primates: ultrastructural observations.

Sympathetic innervation of intraparenchymal blood vessels in the basal ganglia was demonstrated by transmission electron microscopy in arteries, arterioles, and capillaries of the subhuman primate brain. Small arteries (40-120 micron) and some arterioles (12-40 micron) are innervated only at branching sites. However, arterioles occasionally may be innervated at points distal to their origin. Capillary innervation was very infrequently observed.

Animals↗