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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 44-year-old woman with a history of cerebral infarction and hypertension developed sudden onset of speech and visual disturbance. On admission, her general physical examinations showed high blood pressure of 210/120 mmHg and Raynaud's phenomena. The neurological examinations revealed right upper quadratic hemianopsia, left oculomotor nerve paresis and left hyperreflexia. Laboratory findings showed that antinuclear and anti-DNA antibodies were positive. The activity of Fletcher factor was reduced to 50%, and the activated partial thromboplastin time (APTT) was prolonged to 82.6 seconds. And a 1:1 dilution with normal plasma failed to correct the prolonged APTT, indicative of circulating anticoagulant to Fletcher factor. Plasma fibrinogen increased to 500 mg/dl but FDP was normal. The CT scan demonstrated the recurrently developed cerebral infarction in the left occipital lobe. Cerebral angiogram revealed mild atherosclerosis of basilar and bilateral posterior cerebral arteries, but any occlusive lesions were not found. Although she had a history of hypertension, this case suggests the possibility that the disturbance in fibrinolytic system may have been caused by the circulating anticoagulant to Fletcher factor, and contributed to her cerebral infarctions.
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PMID:[A case of cerebral infarction with circulating anticoagulant to Fletcher factor]. 191 33

The development of atherosclerosis includes an abnormal proliferation of smooth muscle cells (SMCs) in the arterial intima. The factors responsible for this process remain to be identified, but earlier studies have suggested that age-related changes in growth-regulatory mechanisms may be involved. In the present study growth-regulatory mechanisms of neonatal and adult rat SMCs have been compared both in early passage and after subcultivation. Neonatal SMCs in early passage were found to have a high rate of spontaneous DNA synthesis and showed little response to stimulation with growth factors. Early passage adult SMCs showed a lower rate of spontaneous DNA synthesis but responded well to exogenous growth factors. There was no difference in the gene or surface expression of receptors for platelet-derived growth factor (PDGF) between neonatal and adult cells, and there was no significant difference in the amount of inositol phosphate formed in the cells after stimulation with PDGF BB. However, there was increased expression of PDGF A chain mRNA in serum-starved neonatal cells as compared to adult serum-starved SMCs. After subcultivation (seven to nine passages) neonatal SMCs started to become senescent, had a low rate of spontaneous DNA synthesis and were more sensitive to growth factor stimulation than in early passage. Adult SMCs did not demonstrate signs of senescence after subcultivation. The results demonstrate marked differences in the mechanisms regulating growth of neonatal and adult rat SMCs and suggest that the increased sensitivity of adult cells to exogenous growth factors and the inability of these cells to become senescent may be important factors in atherogenesis.
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PMID:Differences in growth factor response in smooth muscle cells isolated from adult and neonatal rat arteries. 195 11

DNA samples from 53 unrelated Dutch patients with familial hypercholesterolemia (FH) were screened for rearrangements in the gene for the LDL receptor (LDLR) by Southern analysis. Four different mutations have been detected by hybridisation of BglII digested genomic DNA with an exon 10-14 containing cDNA probe. The mutations are defined by a 7 kb insertion near exon 11, a partial gene duplication encompassing exons 9-12, a 4 kb deletion of exons 7 and 8 and an 0.4 kb deletion comprising the 5'-part of exon 16. These four different rearrangements in the LDLR gene account for 17% of the mutations in the Dutch FH population sample. Interestingly, the 4 kb deletion was detected in 5 unrelated FH patients (9.5%) and appeared to be identical to the deletion previously described (Russell, D.W. et al., Arteriosclerosis, 9 (Suppl. I) (1989) I-8; Russell, D.W. et al., Cold Spring Harbor Symp. Quant. Biol., 51 (1987) 401). in an FH patient of Dutch origin. This suggests that the 4 kb deletion is a common mutation in the Dutch FH population.
Atherosclerosis 1990 Aug
PMID:Rearrangements in the LDL receptor gene in Dutch familial hypercholesterolemic patients and the presence of a common 4 kb deletion. 197 82

Lipoprotein lipase is the rate determining enzyme for the removal of triglyceride rich lipoproteins from the blood stream. We examined whether genetic variation at the lipoprotein lipase gene locus is related to the occurrence of premature coronary artery disease. Two restriction fragment length polymorphisms, revealed by the enzymes HindIII and PvuII, demonstrated alleles designated H1 (17.5 kb), H2 (8.7 kb), P1 (7.0 kb), P2 (4.4 kb and 2.5 kb) respectively. These were studied in 70 Caucasian subjects with severe coronary atherosclerosis in comparison with 122 Caucasian healthy controls. The allelic frequencies for cases and controls were respectively: H2 0.770, 0.579 (P less than 0.001); P2 0.575, 0.554 (P NS). The allelic frequencies of the HindIII and BglII polymorphic sites at the hepatic lipase gene locus were also studied in the same groups of subjects. These showed no differences between cases and controls. We conclude that DNA variation at or adjacent to the lipoprotein lipase gene may contain genetic determinants for the occurrence of premature coronary artery disease.
Atherosclerosis 1990 Nov
PMID:Lipoprotein and hepatic lipase gene variants in coronary atherosclerosis. 198 Aug 16

The present study was undertaken to explore the possibility that neointimal smooth muscle cells, the characteristic cells of restenosis and atherosclerosis, are selectively stimulated to replicate by a hypertensive stimulus. Angiotensin II (AII) was infused by osmotic minipumps for 2 weeks in 4.5-month-old rats. Group A received AII (200 ng/min) 2 weeks after a balloon catheter-induced injury of the thoracic aorta and left common carotid artery. Group B received only AII, group C only balloon denudation, and group D neither balloon injury nor AII. During the AII or Ringer's solution infusion, all animals received [3H]thymidine via a second minipump to measure DNA synthesis. AII increased the systolic pressure by more than 40 mm Hg. AII significantly increased DNA synthesis in the media of the carotid artery from 0.2 +/- 0.2% in group C to 2.5 +/- 1.5% in group A (mean +/- SD, n = 5 or 6). DNA synthesis in the neointima of the carotid artery significantly increased with AII from 4.8 +/- 4.2% in group C to 19.8 +/- 13.9% in group A. Cross-sectional area of the neointima almost doubled during AII infusion, and it increased approximately 25% in the media. Comparable results were obtained in the aorta. In a second experiment, AII was infused (125 ng/min) for 2 weeks in 11-week-old rats. Concomitantly, [3H]thymidine was given. Control rats received Ringer's solution and [3H]thymidine in their pumps. Blood pressures were elevated to the same extent as in the older animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Angiotensin II induces smooth muscle cell proliferation in the normal and injured rat arterial wall. 199 49

Arterial structural changes play a key role in atherosclerosis and hypertension and could become a valid target for pharmacotherapy of these disorders. Current insights in arterial growth control were derived from experiments in cell culture and in experimental animals. In this study, we evaluated growth responses in isolated arterial segments and compared our in vitro observations to arterial changes in experimental models of essential and secondary renal hypertension. In isolated renal artery segments, serum growth factors caused a transient stimulation of DNA synthesis in the arterial media. This in vitro growth response did not lead to media hyperplasia, hypertrophy or hyperploidy. In intact, conscious 6-week-old spontaneously hypertensive rats (SHR), DNA synthesis in the media of large arteries was two to four times larger than that in arteries of age-matched normotensive rats. Yet, the elevated wall/lumen ratio in renal arteries of adult SHR was due to a reduction of the arterial lumen diameter and not to an altered media cross-sectional area. In addition, while aorta-coarctation resulted in a marked increase of renal arterial cross-sectional area it did not alter the number of renal artery smooth muscle cells. These observations indicate that even powerful chemical and mechanical mitogenic conditions do not alter the number of medial smooth muscle cells. This could be due to rapid down-regulation of arterial growth responsiveness, migration, and turnover of cells.
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PMID:Growth responses in the arterial wall. 203 89

In chronic models of hypertension such as the spontaneously hypertensive rat (SHR), thickening of the media of large arteries occurs mainly through smooth muscle cell (SMC) hypertrophy accompanied by DNA replication resulting in large polyploid cells. In resistance vessels of SHR, medial hypertrophy occurs through a hyperplastic response. It has been suggested that this hyperplasia is due to mitogens such as platelet-derived growth factor (PDGF), while the hypertrophied polyploid cells occur from stimulation by angiotensin II from within the vessel wall. Angiotensin II activates many of the same cellular pathways as PDGF, including stimulation of phospholipase C, mobilization of intracellular calcium and activation of Na+/H+ exchange. Both induce transient increases in the proto-oncogenes c-fos and c-myc. However, a possible explanation for the difference in SMC response may be involvement of an intracellular pathway stimulated by PDGF (but not by angiotensin II), such as stimulation of JE (a cytokine-like molecule), which may activate transcriptional events necessary for mitogenesis. In atherosclerosis vascular hypertrophy occurs in the form of focal intimal thickening and results from hyperplasia of diploid SMC and their greatly increased production of extracellular matrix, (particularly collagen) and the accumulation of intra- and extracellular lipid. The SMC involved in atherogenesis are phenotypically modified compared with the SMC of undiseased regions, and amongst other features have a lower volume fraction of myofilaments (Vvmyo). Associated with modulation to a low Vvmyo are increases in SMC expression of mRNA for collagens type I (alpha 1 and alpha 2) and type III (alpha 1), elastin, fibronectin, as well as massive increases in collagen protein (26- to 45-fold), glycosaminoglycans (5-fold), and lipid accumulation (7-fold).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular biology of vascular hypertrophy. 203 94

The current interest in vascular lesions formed during childhood and adolescence is both pertinent and timely, as atherosclerosis research has never been more exciting that at the present. A number of attractive hypotheses about the pathogenesis of atherosclerosis have been proposed which provide different perspectives for understanding the disease process. A host of animal and cell models of early lesions are now available for study and new technological advances, such as recombinant DNA techniques and sensitive imaging procedures, will allow these models to be studied in greater depth. Consequently, the next decade should bring new insight on the pathogenesis of atherosclerosis, especially the early lesions of youth.
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PMID:Cellular models of atherosclerosis in the young. 204 76

The precise pathogenesis of human diabetic kidney disease and the factors responsible for the susceptibility to it remain to be established. However, there is now evidence that renal disease clusters in families and that genetic factors are of central importance in determining liability. A predisposition to arterial hypertension has been suggested as playing a contributory role in the development of kidney disease. Genetically controlled hypertrophic processes may be implicated in the susceptibility to arterial wall damage and glomerular injury in diabetes. This suggestion derives from the observation that the fibroblasts of patients with diabetic nephropathy show a higher Na+/H+ antiport activity and a greater 3H-thymidine incorporation into DNA than fibroblasts of diabetic patients without nephropathy. The first sign of renal damage is the appearance of microalbuminuria and of a small elevation in arterial pressure, changes associated with significant mesangial expansion. Microalbuminuria is associated with abnormalities of lipoprotein profiles possibly as a consequence of insulin-resistance-induced hyperinsulinemia. It could be postulated that the environmental changes brought about by diabetes lead in susceptible individuals to increased systemic and intraglomerular pressure on the one hand and mesangial expansion on the other. These two processes would cause proteinuria and glomerulosclerosis. Lipid abnormalities would further aggravate the renal histological damage and, in combination with hypertension, contribute to the accelerated atherosclerosis typical of patients with diabetic kidney disease. A vicious circle would thus be triggered of reduction in renal function, more hypertension, more proteinuria, more glomerular obsolence, more hyperlipidemia and eventually end-stage renal failure or premature cardiovascular death.
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PMID:Mechanisms of diabetic renal and cardiovascular disease. 207 90

Werner syndrome (WS) is a recessive genetic condition associated with markedly reduced replicative lifespans of cells in culture, high chromosomal instability in vivo and in vitro, and premature appearance of many characteristics of normal aging, including an increased incidence of cancer. We have monitored plasmid homologous recombination frequencies in diploid fibroblasts from 6 Werner or Werner-like syndrome patients, following transfection with a plasmid substrate containing 2 overlapping fragments of the TN5 Neor gene. Plasmid DNA recovered from these cells was then assayed for homologous recombination by (a) transformation of recA- bacteria to Ampr (indicating total viable plasmid) or Neor (indicating viable recombinant plasmid), and (b) by limited-cycle polymerase chain reaction (PCR) to co-amplify a recombinant fragment containing the overlap region, and a control region of the same plasmid, without bacterial transformation. Bacterial assay data indicated that recombination rates in 3 of the 6 WS strains were significantly elevated above normal controls; 4 of 6 appeared elevated by PCR assay. The highest-recombination WS strain showed evidence of reduced degradation of transfected plasmid DNA. For this small sample of WS strains, clinical severity of WS was not well correlated with recombination rate as determined by either assay (Pearson r = 0.78, not significant, for PCR assay); elevated recombination may, however, define a subset of WS at greatest risk for cancer and/or atherosclerosis. PCR assay of a hyperoxia-resistant HeLa cell line, displaying substantially increased chromosome breakage, indicated increased recombination between direct-repeat fragments. Nevertheless, elevated recombination in WS strains is unlikely to be secondary to impaired replicative capacity characteristic of WS cells, or to defective repair of chromosome damage which is increased in WS, since recombination in non-WS strains was unaffected by passage level or repeated UV irradiation.
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PMID:Homologous recombination is elevated in some Werner-like syndromes but not during normal in vitro or in vivo senescence of mammalian cells. 207 65


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