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Biomedical subjects

L Capron

Publications and source records attributed to L Capron.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1989

[Pathogenesis of atherosclerosis: an update on the three main theories].

The causes and mechanisms of atherosclerosis remain incompletely understood. Almost all the present investigations are still connected with one of the main three historical theories of atherosclerosis: 1) the incrustation theory, as developed by von Rokitansky, has now led to the many studies on the roles of thrombosis and platelets; 2) the irritation theory, as opposed to the preceding one by Virchow and his school, is reviving through the rediscovery that leukocytes are present in the plaques, and that atherosclerosis (Virchow's endarteritis chronica deformans sive nodosa) has the features of a chronic inflammatory reaction; 3) the lipid infiltration theory, as initiated by the experiments of Anitschkov and Chalatov in rabbits fed a cholesterol enriched diet, motivates the huge mass of studies devoted to plasma lipids and their cellular metabolism. This article provides a brief update on each of these three complementary approaches of atherosclerosis.

Animals↗
PubMed1989

[Participation of platelets in the progression of atherosclerosis].

The role of platelets in the early steps of atherosclerogenesis is controversial, but it is well established that platelets play a prominent part in arterial thrombosis, the leading event in the progression of atherosclerosis. Ulceration of the plaque breaks the endothelial cover, and induces blood to interact with the deeper components of the lesion, which leads to adhesion, activation and aggregation of platelets at the intimal breach. The resulting clump of platelets becomes a thrombus by further platelet accumulation and the addition of fibrin (through the triggering of the coagulation cascade). The thrombus has three possible fates. 1. It can grow by addition of successive layers of platelet, fibrin, white and red blood cells, until it eventually occludes the arterial lumen, often provoking an ischaemic event (such as a myocardial infarction). 2. At any time of its growth, the thrombus can be dislodged in whole or in part to cause arterial embolism. 3. The thrombotic material may become overgrown by endothelium and incorporated into the intima, becoming part of the atherosclerotic lesion and strongly contributing to the increase of its sclerotic as well as atheromatous (lipid) mass. Although the mechanisms of ulceration remain unclear, the resulting platelet activation leads to mural thrombosis and greatly contributes to the progression and complications of atherosclerosis. Available antiplatelet agents interfere favourably with the atherosclerotic process, but more efficient drugs will be designed when we better understand the mechanisms of ulceration and the influences that modulate the growth and fate of arterial thrombi.

Animals↗
PubMed1989

Influence of applied stress on mitotic response of arteries to injury with a balloon catheter: quantitative study in rat thoracic aorta.

Proliferation of arterial smooth muscle cells is an important feature of atherosclerosis, and a well documented reaction to intimal injury. To assess the influence of the intensity of injury to rat thoracic aorta, we studied the effects of a soft or hard friction with a moderately or tightly inflated balloon catheter at 2, 14 and 30 d after operation. As compared with soft injury, hard injury (1) strongly enhanced the proliferating response of the aortic intima and media (median incorporation of tritiated thymidine into deoxyribonucleic acid on day 2 increase 2.8-fold, 95% confidence interval 2.3-3.3; median deoxyribonucleic acid content on day 14; 102.1 v 72.1 micrograms); (2) markedly delayed endothelial regeneration (median percentage of intimal area stained by Evans blue on day 14: 33.1 v 0.6%). On day 2, transmission and scanning electron microscopy showed that endothelial denudation was complete after a hard injury, but only partial after a soft one. However, macroscopic staining of the intima with Evans blue was complete in both instances. The extent of endothelial denudation appears to be a major determinant of the mitotic reaction of arteries to injury. In the experimental search for drugs to reduce muscular proliferation (of potential value in the prevention of restenosis after percutaneous transluminal angioplasty), endothelial injury with balloon catheters should be carefully standardised, and applied "blindly" to afford valid comparisons between treated and control groups of animals.

Animals↗
PubMed1989

[Inflammation and atherosclerosis].

Inflammation is the reaction of a vascularized living tissue to local injury. Acute and chronic inflammation result from complex interactions between leukocytes, mesenchymal cells and various components of plasma. The aim of inflammation is reparation, but persisting chronic inflammation is a source of disease. Atherosclerosis can be viewed as an impairment of the normal relationships between blood and arterial wall. As proposed by pathologists of the last century, inflammation may provide a physiopathologic frame for atherosclerosis. Human atherosclerotic lesions at any step of their evolution, as well as the pathogenic models that have been developed to explain atherogenesis, share many features of an inflammatory reaction of arterial intima: increased penetration of plasma components, proliferation of smooth muscle cells, infiltration by monocytes/macrophages and by lymphocytes, building up of a sclerotic extracellular matrix and of a rich neovascularization. The inflammatory model neither contradicts nor jeopardizes the established knowledge on the roles of lipids and thrombosis in atherosclerosis. Rather, introducing the numerous cellular and molecular mediators of inflammation into the pathogenesis of atherosclerosis widens our field of investigations, and may open new avenues for prevention and treatment. There remains the major question of identifying the cause(s) which initiate(s) and perpetuate(s) arterial inflammation that lead to complicated atherosclerosis with ischemic manifestations.

Arteriosclerosis↗