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Biomedical subjects

L Capron

Publications and source records attributed to L Capron.

At least 19 recordsLinked to original sources
PubMed2003

What's in a risk factor? "He who strikes the ball".

A major aim of epidemiology is to explore the prognosis and aetiology of diseases, in order to improve treatment and prevention. To avoid misleading interpretations of observed associations between a modifier and the occurrence of a disease, the all-purpose idiom "risk factor" should be replaced by 3 locutions with narrower meanings: a risk marker is a modifier which is associated (correlated) with disease prevalence (case-control studies) or incidence (cohort studies); a risk marker truly becomes a risk factor if its experimental correction (intervention studies) does improve the disease incidence or prognosis; a risk factor is promoted to the rank of cause if it is proved to be necessary (sine qua non) for the occurrence of the disease. A more rigorous vocabulary avoids premature claims for unsubstantiated treatments or preventions, and helps defining sound priorities in aetiological research.

Adult↗
PubMed2001

Transient down-regulation of L-type Ca(2+) channel and dystrophin expression after balloon injury in rat aortic cells.

OBJECTIVE: Migration and proliferation of arterial smooth muscle cells are critical responses during restenosis after balloon angioplasty. We investigated the changes in the expression of Ca(2+) channels and dystrophin, two determinants of contraction, after balloon injury of rat aortas. METHODS: Proliferation and migration of aortic myocytes were triggered in vivo by the passage of an inflated balloon catheter in the aortas of 12-week-old male Wistar rats. We used the whole-cell patch clamp technique to investigate Ba(2+) currents (I(Ba)) through Ca(2+) channels in single cells freshly isolated from media and neointima at various times after injury (days 2, 7, 15, 30 and 45). RESULTS: No T-type Ca(2+) channel current was recorded in any cell at any time. In contrast, a dihydropyridine (DHP)-sensitive L-type I(Ba)was recorded consistently in the media of intact aorta. After aortic injury, I(Ba) decreased dramatically (at days 2 and 7) but recovered over time to reach normal amplitude on days 30 and 45. In the neointima, I(Ba) was absent on day 15 but also increased gradually over time as observed at days 30 and 45. The use of a specific antibody directed against the L-type Ca(2+) channel alpha(1C) subunit showed, both by immunostaining and by Western blotting, no expression of the Ca(2+) channel protein on day 15. Parallel immunodetection of dystrophin showed that this marker of the contractile phenotype of SMCs was also not detectable at this stage in neointimal cells. Both proteins were re-expressed at days 45 and 63. Balloon injury induces a transient down-regulation of I(Ba) in arterial cells. CONCLUSIONS: Cell dedifferentiation and proliferation in vivo abolish the expression of L-type Ca(2+) channels and dystrophin in neointimal cells. These changes may be critical in the regulation of Ca(2+) homeostasis and, thereby, contraction of the arterial SMCs during restenosis following angioplasty.

Angioplasty, Balloon↗
PubMed1999

[Etiology of atherosclerosis].

The object of aetiology is to unveil causes, conditions that are necessary (although not sufficient) for the occurrence of a disease. No authentic cause of atherosclerosis has been identified yet. So far, aetiologic research has only established risk factors, modifiable conditions that are neither necessary nor sufficient, which provide efficient but incomplete means for prevention. Other aetiologic tracks must be explored, where the levers for truly mastering atherosclerosis are to be found. Infection is but one example which is presently the object of keen interest, but remains quite far from definitive proof.

Arteriosclerosis↗
PubMed1998

Galectin-3 gene (LGALS3) expression in experimental atherosclerosis and cultured smooth muscle cells.

The galectin-3 gene (LGALS3) encodes a beta-galactose binding lectin. LGALS3 expression is associated with neoplastic transformation and with differentiation of monocytes to macrophages. Factors involved in migration, proliferation, adhesion and differentiation of vascular smooth muscle cells (SMC) play a major role during atherosclerosis development. Expression of the galectin-3 gene was not detected in quiescent SMC but was activated in aortas of hypercholesterolemic rabbits, in aortas of rats after balloon injury and in cultured SMC. These results suggest that galectin-3 production is involved in the developmental process of atherogenesis.

Animals↗
PubMed1998

Insulin-like growth factor-1 stimulates vascular smooth muscle cell proliferation in rat aorta in vivo.

IGF-I is a mitogen for vascular smooth muscle cells (SMC) in vitro and enhances SMC proliferation in vivo in diabetic rats. In this study, we examined the effect of IGF-I on SMC proliferation in vivo in normal rats. Recombinant human IGF-I (0.87 and 3.1 mg/kg/day), was infused via osmotic minipumps in normal rats starting 3 days before they were subjected to aortic injury with a balloon catheter. IGF-I at an infusion rate of 3.1 mg/kg/day caused a significant increase in 3H-thymidine incorporation into DNA (+53%, P < 0.01) in the rat aortic intima-media 2 days after injury and DNA content (+13%, P < 0.05) after 11 days. The elastin and collagen contents were not changed by IGF-I infusion after 11 days. Body weight increased slightly while blood glucose was not affected. At an infusion rate of 0.87 mg/kg/day, IGF-I had no significant effects. These results suggest that circulating levels of IGF-I can stimulate SMC proliferation in vivo in normal rats but only at high concentrations.

Animals↗
PubMed1998

[The infection theory in atherosclerosis].

Atherosclerosis displays all the features of a chronic inflammatory process. Aggressions that ignite and fuel atherosclerotic inflammation warrant keen attention. Infection is a potential clue, implying microbes with certain discrete characteristics: a wide epidemiologic distribution, a tropism for the arterial wall, and an aptitude for persistence, latency and recurrence. The infectious theory has built up from the pioneering observations of Fabricant et al. (1978) on the arterial lesions provoked by Marek's disease herpesvirus in chicken. So far one virus (cytomegalovirus) and two bacteria (Chlamydia pneumoniae and Helicobacter pylori) have been implicated in human atherosclerosis, based upon experimental, sero-epidemiologic, or pathologic evidence. None of these potential contributions has yet been established beyond reasonable doubt. However, grounded on the suspicion about C. pneumoniae, provocative therapeutic evidence has added recently: according to two pilot studies, treatment with macrolide antibiotics appear to improve the prognosis of coronary artery disease in both its chronic and acute forms. If ongoing larger-scale studies confirm these preliminary results, a novel era will open in our capacity for explaining, treating and preventing atherosclerosis. An infectious aetiology of atherosclerosis is now to be considered earnestly, and is already being submitted to more intensive clinical and experimental investigation.

Arteriosclerosis↗
PubMed1997

[Severe hemorrhagic complications during treatment with low molecular weight heparin. Apropos of 2 cases].

Two cases of fatal bleeding in patients treated with low molecular weight heparin for deep vein thrombosis are reported. Risk factors for bleeding were: severe underlying disease (cancer in one case, morbid obesity and cardiac failure in the other), age over 80 years and worsening of renal insufficiency in both cases, recent surgical procedure in one case. Anti-Xa activity was beyond the therapeutic range at the time of bleeding in both cases. The usefulness of biologically monitoring the treatment of deep vein thrombosis with low molecular weight heparin is discussed.

Aged↗
PubMed1997

Overexpression of P2Y2 purinoceptor in intimal lesions of the rat aorta.

Extracellular nucleotides, particularly ATP, are involved in the modulation of arterial vasomotricity via P2 purinoceptors present on smooth muscle and endothelial cells. These nucleotides could also be implicated in the smooth muscle cell hyperplasia observed in intimal lesions. In this study, we tried to define the potential role of the P2Y2 (P2u) purinoceptor by studying its expression in normal and balloon-injured rat aortas. The cloning of a rat P2Y2 cDNA from a rat smooth muscle cell cDNA library made it possible to study P2Y2 expression both by Northern blot and in situ hybridization. Northern blot experiments indicated that P2Y2 mRNA was present in rat medial aortic smooth muscle and in cultured rat aortic smooth muscle cells. In situ hybridization indicated that P2Y2 mRNA was present in endothelial cells of the intima and in some smooth muscle cells scattered throughout the media of adult rat aortas, while almost all medial smooth muscle cells of rat embryo aorta expressed this receptor. In contrast with adult aortic media, the majority of neointimal smooth muscle cells found in aortic intimal lesions either 8 or 20 days after balloon injury were positive for P2Y2 mRNA. Moreover, a subpopulation of neointimal cells localized at the luminal surface could be identified by a higher P2Y2 expression than the underlying neointimal smooth muscle cells. These data showing a strong expression of the P2Y2 purinoceptor in the neointima of injured arteries suggest that extracellular nucleotides may be involved, via this receptor, in the intimal hyperplasia and/or chronic constriction observed at the lesion site, and consequently in the restenotic process.

Amino Acid Sequence↗
PubMed1997

Repeated balloon injury of rat aorta. A model of neointima with attenuated inhibition by heparin.

Repeated arterial injury, because it challenges already activated cells, may elicit a reaction that differs from that provoked by a single injury. We compared the response of rat aorta to single and double balloon injury and tested the inhibitory effect of heparin in both situations. For repeated injury, the first and second lesions were induced 3 weeks apart. Two weeks after repeated injury, the neointima that existed from the first lesion had expanded, with significant increases in intima-media wet weight and its DNA and elastin content and in the intima-to-media (I/M) thickness ratio. Two days after repeated injury, the expression of proliferating cell nuclear antigen (PCNA) was enhanced in both the media and the intima, indicating that cells from both layers are involved in the aortic response to a second lesion. As established previously, treatment with heparin (continuous intravenous administration, 50 IU/kg.h-1) almost totally suppressed the response to single injury. However, heparin only attenuated the response to repeated injury, with a partial decrease in intima-media wet weight and its DNA and elastin content and in I/M thickness ratio. PCNA labeling showed that heparin inhibited the proliferative activity in medial cells much more strongly than in intimal cells. In conclusion, repeated aortic injury elicits a reaction of both the media and preexisting neointima. In this mixed response, neointimal smooth muscle cells are less sensitive than medial cells to inhibition by heparin, which results in a weakened effect of the drug on the fibromuscular reaction.

Animals↗
PubMed1996

[Atherosclerosis and cardio-vascular complications of diabetes].

Diabetic macroangiopathy comprises: on one hand, atherosclerosis which seems to appear earlier and to progress more rapidly than in non-diabetic individuals; and, on the other hand, a less well characterised involvement of arteries affecting their structure (diffuse fibrosis) and function (vasomotility). Hyperinsulinaemia is suspected to enhance macroangiopathy, yet the biological and epidemiological facts to support this hypothesis are weak and somewhat discrepant. By contrast, a role for hyperglycaemia, in terms of intensity and duration, is supported by growing evidence. In addition to the correction of classical risk factors for arterial disease, the strict control of hyperglycaemia is likely to become an essential intervention in the prevention of macroangiopathy.

Adolescent↗