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Biomedical subjects

J Larrue

Publications and source records attributed to J Larrue.

At least 37 records · Page 2Linked to original sources

Detection of atherosclerotic plaque with two monoclonal antibodies. 2P1A2 monoclonal antibody is specific for smooth muscle cells in atherosclerotic plaque.

We investigated two monoclonal antibodies (MAbs) which recognize rabbit atherosclerotic tissues. In particular, one antibody, 2P1A2, is specific for rabbit aortic smooth muscle cells (RASMCs). We used RASMCs in primary culture to produce and screen MAbs directed towards the cell surface. The specificity of the described antibodies was tested on a battery of tissue cryosections of different origin (rabbit, rat and human) by immunological staining. 2P1A2 shows an exclusive immunolabeling for SMCs present inside rabbit atherosclerotic plaque. This MAb shows inside the fibrous plaque a staining similar to two other SMC-specific antibodies (anti-desmin and anti-alpha-actin). In an early stage of atherosclerosis, close to the internal elastic lamina, underlying a fibrous plaque, 2P1A2 detects some SMCs; in contrast, anti-desmin and anti-alpha-actin fail to stain such SMCs. This antibody may be therefore considered as directed specifically against SMCs in an activated state. The other antibody which we describe, 1PC1, stains a pericellular antigen expressed by cultured SMCs and shows a specificity for smooth muscle tissues. 1PC1 MAb strongly stains the fibrous plaque of atherosclerotic rabbit aorta and the recognized epitope is present inside the aortic media. These two antibodies may be useful in the recognition of vascular SMCs during the atherosclerotic process.

Animals↗

Serum type III procollagen peptide levels in coronary artery disease (a marker of atherosclerosis).

The known shift in collagen synthesis from procollagen type I to type III in patients with atherosclerosis, suggested measurement of serum procollagen III peptide (PIIIP) levels in patients with coronary artery disease (CAD). Two groups of patients were studied: group I--thirty-six patients with CAD (male, mean age 56.9 +/- 7.5 years, hospitalized for coronary angiography. Risk factors included 16 patients with high blood pressure, four diabetics, 31 smokers and 15 with hypercholesterolaemia. Five patients had no significant lesions, seven had one vessel with over 50% stenosis, 10 had two vessels and 14 had three vessels. Group II--35 patients (male, mean age 39.4 +/- 13.3 years), with normal physical examination and ECG according to WHO criteria, formed the control group: the risk factors included nine patients with high blood pressure, 14 smokers and one with hypercholesterolaemia. Procollagen III peptide levels were determined by radioimmunoassay. In group I, PIIIP levels were 26.8 +/- 16 ng ml-1 vs. 10.4 +/- 3.2 for group II. Sixty-one per cent of group I had pathological levels of PIIIP with an absence of correlation with the severity of atherosclerosis or risk factors. Only 2.8% of patients in group II had pathological levels. Procollagen III peptide determination would appear to be a sensitive, specific and predictive test for atherosclerosis in patients with CAD.

Adult↗

[Smooth muscle cells express in culture a surface antigen identified by a polyclonal anti-actin antibody].

These results demonstrate the presence of actin on the surface of smooth muscle cells in culture. The expression of surface actin is modified by drugs (calcium, ionophore A 23187, LTB4) involved in cell metabolism. Actin exists also in intracellular cytoskeleton and extracellular matrix and is a smooth muscle differentiation marker that may be related to adhesion and cell locomotion.

Actins↗

Cicletanine and eicosanoids in cultured vascular smooth muscle cells.

Cicletanine, a new antihypertensive, slightly diuretic, drug was tested for its effects on arachidonic acid (AA) metabolism in cultured smooth muscle cells from rat aorta. Cicletanine significantly enhanced the production of prostacyclin from both exogenously added arachidonic acid and endogenous sources. This effect is not mediated through inhibition of the lipoxygenase pathways and occurs despite a slight but definite inhibition of the activity of acyl hydrolase. Taken together, these results indicate that the antihypertensive properties of cicletanine might be associated, at least in part, with activation of the AA cascade through the cyclooxygenase pathway.

Animals↗

[Protease inhibitors and ectasia in coronary atherosclerosis].

The possibility of elastase contributing to degradation of the arterial wall in atherosclerosis and to the formation of ectasia has prompted us to assay the main protease inhibitors, alpha 1-antitrypsin and alpha 2-macroglobulin, in patients with angiographic coronary disease with and without coronary ectasia. Serum concentrations of these two proteins were measured by immunonephelometry in 203 patients admitted for coronary arteriography. The results obtained were analyzed according to the presence of atheromatous lesions and their severity and to the presence or absence of ectasia. There was no correlation between the values observed and the presence or severity of coronary atherosclerosis, but the concentration of alpha 1-antitrypsin was significantly higher in patients with coronary ectasia (247.2 +/- 40.5 mg/ml) than in patients without ectasia (213.5 +/- 36.6 mg/100 ml; p less than 0.001). This study shows that coronary ectasia is associated with disturbances in the protease-antiprotease system, which may be consecutive to initial changes in elastase activity. Our results support the theory that elastase and protease inhibitors play a specific role in some atheromatous processes.

Adult↗

Hemorheological changes in elderly subjects--effect of pentosan polysulfate and possible role of leucocyte arachidonic acid metabolism.

The effects of pentosan polysulfate (PPS) on various hemorheological parameters were studied in a group of very elderly subjects in good general health. Alterations in blood viscosity and filterability were detected in these patients, without any concomitant changes in factors which are known to affect these parameters: notably hematocrit, fibrinogen and plasma lipid levels. The hemorheological abnormalities were considerably improved by twice daily treatment with 50 mg of PPS (i.m.). Apart from its anticoagulant activity, PPS has been shown to have an anti-inflammatory action. We were interested to investigate its effects on metabolism of exogenous arachidonic acid (AA) by both platelets and leucocytes. It is becoming increasingly recognized that metabolites of AA via the 5 LO pathway appear to play a role in inflammatory processes. In this study, PPS was found to inhibit leucocyte 5 LO activity. Reduction in the levels of these metabolites may therefore have an effect on whole blood rheology.

Adult↗

Megakaryopoiesis disturbances in atherosclerotic rabbits.

Rabbits given a hypercholesterolemic diet (500 mg/day) for 6 months and then maintained for another 6 months on a normal diet were found to have developed fibrous lipidic lesions in the aorta. Although circulating platelet levels in these animals were normal there was a reduction in mean megakaryocyte ploidy. The high concentrations of megakaryoblasts in all the sedimentation fractions collected by the 'STAPUT' system suggested an increase in megakaryocyte turnover with activation of committed stem cells. In addition, other defects in maturation of megakaryocytes were observed, such as abnormalities in the demarcation membrane system and granule number. These data reveal that defects in megakaryocyte maturation and turnover may occur during the process of reparative fibrosis of the arterial tree following a period of moderate hypercholesterolemic diet in the rabbit.

Animals↗

[Metabolism of collagen in coronary patients].

The alterations observed in connective tissue of the arterial wall and dermis in atherosclerosis incited us to investigate collagen metabolism in patients with coronary disease. We first studied collagen metabolism in fibroblast cultures, then measured serum levels of type III procollagen aminoterminal peptide. Fibroblast collagen metabolism was investigated in 12 consecutive patients of less than 45 years of age presenting with coronary disease and coronary atherosclerosis was found to be preserved in patients with atherosclerosis, but less type III type I procollagen was synthesized (14.6 +/- 6.6% versus 22.3 +/- 4.3%). This abnormality, found in 83% of our coronary patients, seemed to be unrelated to risk factors or to the severity of atherosclerosis. Serum type III procollagen aminoterminal peptide was assayed comparatively in 36 patients with coronary atherosclerosis confirmed at coronary-ventriculography and in 35 patients free from coronary disease as defined by the W.H.O. criteria. Serum levels of this peptide were significantly higher in patients with coronary atherosclerosis (26.76 +/- 16 ng/ml) than in controls (10.43 +/- 3.18 ng/ml). 61% of coronary patients had a peptide level higher than the normal value (17 ng/ml). No correlation was found between this rise in type III procollagen aminoterminal peptide and the severity of coronary lesions or the importance of risk factors. Thus, collagen metabolism is altered in coronary patients, and this alteration can be detected by a peripheral marker. However, the use of this marker to diagnose the presence or evaluate the course of atherosclerosis requires clarification.

Adult↗

[Effects of SIN-1 on the metabolism of arachidonic acid in vascular smooth muscle cells in culture].

The effects of SIN-1 on the metabolism of Eicosanoids (prostaglandins, hydroxylated derivatives) were investigated in cultured arterial smooth muscle cells. These cells can use arachidonic acid in two different metabolic pathways involving cyclooxygenase and lipoxygenases activities and leading to the formation of prostaglandins (mainly PGI2) and hydroxylated derivatives (HHT and 11, 15, 12 and 5 HETES). Results shows that SIN-1 produces no modification in PGI2 production, whether under baseline conditions or in the presence of activators for the cell type under study. SIN-1 seems to have no direct action on the sequence of enzyme activities (cyclooxygenase, lipoxygenases). However, SIN-1 significantly alters the distribution of 14C arachidonic acid within membrane structures.

Animals↗

[Mitral valve prolapse and pectus excavatum. Expressions of connective tissue dystrophy?].

Pectus excavatum is a common malformation in diseases of elastic tissue (Marfan, Ehlers-Danlos...). When observed apparently alone it may represent a minor form of dystrophy, implying the same risk of a cardiac lesion. Abnormalities of the thoracic skeleton and echocardiographic mitral valve prolapse is a well established association, suggesting a common disorder of connective tissue. However, there is no absolute proof that this is a statistically significant association. Histological connective tissue changes relating these two markers have yet to be found. Clinical and echocardiographic examinations and skin biopsies were performed in 17 patients with pectus excavatum. Mitral valve prolapse was detected in 65% of cases (associated in 1 out of 3 cases with tricuspid valve prolapse). In 53% of cases electron microscopy showed abnormal skin collagen and elastin. Collagen abnormalities were twice as common as those of elastin and could be associated. Mixed changes of thinning of elastin and collagen fibres of irregular calibre were particularly suggestive. Pectus excavatum would therefore seem to be the expression of a minor form of dystrophy of collagen and elastin tissues and a clinical marker of possible mitral valve prolapse.

Adult↗