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L Capron

Publications and source records attributed to L Capron.

At least 19 recordsLinked to original sources
PubMed1992

Partial characterization of an autoantibody recognizing the secondary binding site(s) of thrombin in a patient with recurrent spontaneous arterial thrombosis.

A patient with an 18 year history of recurrent arterial thrombosis and no evidence of atherosclerosis or embolism of cardiac origin presented with a prolonged thrombin clotting time when performed with human thrombin. The bovine thrombin clotting time was only slightly prolonged. During 30 months of follow-up, the thrombin time fluctuated, but remained prolonged. The patient has been treated with an oral anticoagulant for the past 8 years, with no thrombotic recurrence. The inhibitor activity was due to the presence of polyclonal IgGs which bound to thrombin-Sepharose. The influence of IgGs purified from the patient's serum was compared to the influence of normal IgGs in several systems exploring the catalytic activity of thrombin and the binding of the enzyme to macromolecular substrates through secondary binding site(s). We found that the IgGs did not impair the catalytic activity toward small synthetic substrates, but inhibited the binding of thrombin to fibrinogen, thrombomodulin and heparin cofactor II. Such proteins are known to require a secondary binding site of thrombin to interact with the enzyme. The anti-thrombin antibody might have resulted from an abnormal generation of thrombin. This would be the consequence of the process favouring thrombosis. Alternatively, the autoantibody might have favoured thrombosis primarily, by impairing natural antithrombotic mechanisms triggered by thrombin.

Adult↗
PubMed1992

In vivo proliferation of rat vascular smooth muscle in relation to diabetes mellitus insulin-like growth factor I and insulin.

The roles of diabetes mellitus, insulin-like growth factor I and insulin in vascular smooth muscle proliferation in vivo were studied. Proliferation was induced by endothelial injury (balloon catheterization) of rat aorta, and was measured as 3H-thymidine incorporation into DNA. Levels of insulin-like growth factor I mRNA and insulin-like growth factor I receptor mRNA were measured with a solution hybridization assay. The increase in DNA synthesis was most pronounced 2 days after injury in both normal and diabetic rats and declined thereafter, but DNA synthesis in aortas from diabetic rats was lower throughout the time period studied. Levels of insulin-like growth factor I mRNA and the receptor mRNA were both increased in balloon catheterized aortas, and time-course studies showed an increase in receptor mRNA prior to the increase in insulin-like growth factor I mRNA. Diabetic rats were treated with equimolar concentrations of insulin (35 nmol/day) or insulin-like growth factor I (31 nmol/day) for 5 days. Insulin-like growth factor I increased DNA synthesis in injured aortas 2 days after injury without improving blood glucose, whereas the effect of insulin was associated with a decrease in blood glucose levels. In conclusion, vascular smooth muscle proliferation is impaired by diabetes and stimulated by insulin treatment. Insulin-like growth factor I infusion stimulates vascular smooth muscle proliferation without affecting blood glucose, and gene expressions of insulin-like growth factor I and its receptor are increased in proliferating vascular smooth muscle, indicating that insulin-like growth factor I and involved in vascular smooth muscle proliferation in vivo.

Animals↗
PubMed1992

In vivo effect of insulin on the acute proliferative response of the rat aorta to injury.

The objective of our study was to investigate the effect of hyperinsulinemia associated with either euglycemia, hypoglycemia, or hyperglycemia on the short-term mitotic activity of arterial smooth muscle cells (SMCs) after aortic injury. The proliferative reaction of arterial SMCs was provoked by the passage of an embolectomy catheter with a tightly inflated balloon. DNA synthesis was measured as DNA specific activity after incubation of the aorta in a medium containing 3[H]thymidine. Unrestrained rats were rendered hyperinsulinemic (4-7 nM versus 0.3 nM in controls) immediately after aortic injury by insulin infusion (10 units/day) and either euglycemic (about 5.6 mM), hyperglycemic (14-17 mM), or hypoglycemic (about 2.8 mM) by adjusting the flow rate of hypertonic glucose (30% wt/vol) that was infused simultaneously. The infusion was performed via a catheter inserted into the jugular vein and lasted 2 or 4 days after the aortic injury. After the injury, SMC mitotic activity was dramatically increased on day 2 in control rats with deendothelialized aortas and declined between days 2 and 4. In euglycemic-hyperinsulinemic and hyperglycemic-hyperinsulinemic rats, SMC proliferation showed the same pattern as in controls. At no time was a significant difference observed among the three groups of rats. In hypoglycemic-hyperinsulinemic rats, SMC mitotic activity increased to a lesser extent than in controls on day 2 after deendothelialization. These data indicate that hyperinsulinemia with or without hyperglycemia does not stimulate the early stages of arterial SMC proliferation in the rat although a long-lasting effect of hyperinsulinemia cannot be excluded.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effect of ramipril, an inhibitor of angiotensin converting enzyme, on the response of rat thoracic aorta to injury with a balloon catheter.

We have studied the effect of ramipril (10 mg/kg daily by gastric gavage) on the development of neointima 2 and 14 days after injury to rat aorta with a balloon catheter. In treated animals, there was no significant inhibition of the early mitotic reaction after injury (synthesis of DNA, as reflected by aortic thymidine incorporation on the second day): the mean (95% confidence interval) was 3,553 (892) in the control group vs. 2,853 disintegrations/min/micrograms of DNA (555) in the treated group, 2 p greater than 0.15. However, ramipril decreased the amount of neointima formed 14 days after injury, as characterized by (a) a highly significant decrease of the intima to intima + media areas ratio [21.1 (2.4) vs. 13.7% (2.2), 2 p less than 10(-4]); (b) a significant decrease of intima-media wet weight [35.4 (1.0) vs. 30.9 mg (0.9), 2p less than 0.005]; and (c) without any significant effect on intima-media DNA content [96.3 (7.9) vs. 91.7 micrograms (5.7), 2p greater than 0.3]. These observations suggest that angiotensin converting enzyme inhibitors may not act mainly through an inhibition of smooth muscle cell proliferation. Other effects, such as inhibition of migration, hypertrophy, and matrix synthesis, should also be considered.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Effects of fasting and refeeding on the proliferative response of rat aorta to injury.

To explore the interplay between the mitotic activity of arterial smooth muscle cells and the variations of plasma glucose and insulin concentrations, we have studied over 14 days the response of thoracic aorta to injury with a balloon catheter in rats submitted to fasting and refeeding. Animals were fasted from the day before until the third day after injury. The proliferative reaction of intima-media was assessed 2, 3.5, 4, 6, 8, and 14 days after injury, comparing freely fed with fasted-refed rats. Fasting decreased plasma glucose and insulin concentrations and DNA synthesis by intima-media, whereas refeeding increased these three variables transiently. The DNA content of intima-media at any time during the response to injury and the intimal thickening on day 14 were not influenced by the sequence of fasting and refeeding, which suggests that the early decrease in DNA synthesis induced by fasting had been compensated for by the later increase in DNA synthesis induced by refeeding. In conclusion, besides hormonal influences (such as insulin), metabolic influences (such as the availability of energetic fuels) are likely to act on the proliferative response of arteries to injury.

Animals↗
PubMed1991

[Leukocytes and arteriosclerosis].

Human atherosclerotic plaques contain two type of leucocytes: 1. Monocytes/macrophages comprise almost two thirds of the cells in the center of the lesion (lipid core), and a quarter of the cells in its periphery (fibrous cap); 2. T lymphocytes comprise 10 to 15% of the plaque cells. Polymorphonuclear granulocytes are only present in very small number. The abundance of leucocytes, together with sclerosis and proliferation of mesenchymatous cells (arterial smooth muscle cells), confer to atherosclerosis the aspect of a chronic inflammatory reaction, a fact which has been recognised for a long time. Monocytes/macrophages may contribute to the development of atherosclerosis in several ways: stimulation of the fibro-muscular reaction, endothelial injury, accumulation of intimal lipids. The role of T lymphocytes is still poorly understood. According to some observations, they might be involved in an immunological reaction of the arterial wall which could be determinant in the evolution of the lesion. Arterial leucocytes have somewhat complicated, but also widened our pathogenic hypotheses of atherosclerosis. A major issue now is to identify the nature of the arterial aggressions which provoke the involvement of leucocytes, and the reasons why the defences they oppose are overwhelmed to result eventually in severe thrombo-occlusive events. Recent evidence has strengthened the possibility that viral infection plays a role in atherosclerosis. Beyond their pathogenic interest, these acquisitions might soon provide interesting therapeutic approaches.

Arteriosclerosis↗
PubMed1991

[Normal and pathologic growth of arterial smooth muscle].

In addition to contractility, arterial smooth muscle cells, like all connective tissue cells, have a capacity to proliferate and synthesize extracellular matrix. Under different normal (development, aging) and abnormal circumstances (high blood pressure, atherosclerosis, balloon angioplasty), smooth muscle cells express these properties which characterize the dedifferentiated phenotype. This paper reviews the main mechanisms, modulations and possible therapeutic implications of dedifferentiation.

Arteries↗
PubMed1990

[Viruses and atherosclerosis].

Our understanding of the pathogenesis and aetiology of atherosclerosis remains incomplete. An infection by herpesviruses is among the plausible hypotheses. In chicken, inoculation with Marek's disease virus provokes arterial lesions closely resembling atherosclerotic plaques. Experiments done on cultured arterial cells have shown that herpesviruses might enhance atherogenesis. Herpesviruses molecules (proteins, messenger ribonucleic acid, deoxyribonucleic acid) are commonly found in the human arterial wall. According to a recent study using gene amplification by the polymerase chain reaction, the complete cytomegalovirus genome can be detected in 90 p. 100 of the samples from atherosclerotic plaques and in 53 p. 100 of the samples from normal arterial wall. Cytomegalovirus infection appears to increase the risk and severity of atherosclerotic lesions which develop in heart grafts and compromise their survival. These data are not sufficient to prove that herpesviruses, especially cytomegalovirus, play a causal role in human atherosclerosis. The viral hypothesis, however, must be considered as serious and is certainly worth further investigations.

Animals↗
PubMed1990

A plasma clot lysis assay based on the release of fibrin degradation products: application to the diagnosis of hypofibrinolytic states.

Using a monoclonal antibody-based assay, we measured the fibrin degradation product release in the supernatant of plasma clots obtained before and after venous occlusion (VO) in 30 patients with definite or suspected vascular thrombosis (19 definite and 2 suspected deep vein thrombosis, 6 recurrent superficial thrombophlebitis, 3 arterial occlusions of lower limbs). tPA and PAI-1 concentrations were determined using ELISA assays; the post-occlusion values were corrected for haemoconcentration. The increase in tPA during VO was correlated with haemoconcentration (r = 0.74), but 3 patients had ineffective VO (less than 2% increase in proteins). The fibrinolytic response to VO was evaluated using the shortening of the time necessary for the release of 200 micrograms of fibrin degradation products per mg of fibrinogen (delta T 200). Two among the 27 patients with effective VO were bad responders with a delta T 200 less than 3 h (whereas all the others had delta T 200 greater than 10 h). These patients had respectively a deficient tPA release (delta tPA = 1 ng/ml) and an elevated PAI-1 level at rest (33 ng/ml). Several other patients were bad responders in terms of tPA release or of shortening of the euglobulin clot lysis time but they had a normal delta T 200. This plasma clot test reflects the ability of free tPA to bind to fibrin (the amount of which depends on the level of tPA and PAI-1), and may be useful in the diagnosis of a hypofibrinolytic state.

Adult↗
PubMed1990

[Up-date on atherosclerosis].

The major steps of the pathogenesis of atherosclerosis are now well defined. Efforts are still required to better characterize: 1. the cellular mechanisms of atherogenesis, without ignoring the limitations of the available experimental models; 2. the complications of human atherosclerosis, ie the events (ulceration, thrombosis) that provoke ischaemic manifestations. Four short reviews on topics of special interest follow: proliferation of arterial smooth muscle cells; interactions of blood cells (platelets, leukocytes) with the arterial wall; lipoproteins in the genesis of foam cells; recent progresses in genetic epidemiology of cardiovascular diseases.

Animals↗