Biomedical subjects

Michel Desnos

Publications and source records attributed to Michel Desnos.

22 records · Page 2Linked to original sources

PubMed2003

Polymorphisms of genes of the cardiac calcineurin pathway and cardiac hypertrophy.

The study investigated the role of genetic polymorphisms in four genes of the calcineurin pathway on cardiac hypertrophy and dilated cardiomyopathy. The cardiac calcineurin pathway has been suggested to play a role in the development of cardiac hypertrophy in response to a number of physiological and pathological stimuli. Calcineurin, a heterodimeric protein composed of a catalytic and a regulatory subunit, activates the nuclear factor NFATC4 which after translocation to the nucleus associates with the transcription factor GATA4 to activate several cardiac genes involved in hypertrophic response. We have screened the genes encoding the four major components of the heart calcineurin pathway in 95 individuals and identified 27 polymorphisms. These polymorphisms were investigated in 400 selected subjects obtained from a population-based study (LOVE) in relation to echocardiographic parameters. A Gly/Ala substitution at position 160 of the NFATC4 protein (G160A) was associated with left ventricular mass and wall thickness (P=0.02 and 0.006, respectively, GA+AA vs GG), the minor allele (Ala) being associated with lower mean values of these parameters. The other polymorphisms identified by the gene screen were not associated with cardiac phenotypes. For the G160A polymorphism in NFATC4, genotype frequencies were compared between patients with dilated cardiomyopathy and controls obtained from the CARDIGENE Study. Allele A carriers were less frequent in the patient than in the control group (P=0.04). Although the strength of the associations was rather weak, these observations raise the hypothesis that the G160A polymorphism of the NFATC4 gene plays a role in the development of human cardiac hypertrophy.

Calcineurin↗

PubMed2002

[Epidemiology of heart failure].

Prevalence of heart failure is ranging in European countries between 0.4% to 2%. It increases rapidly with age. The number of patients in heart failure reaches 500,000 in France and there are 120,000 new cases every year. Two-thirds are older than 74 years. 3.5 million of outpatients clinics and 150,000 hospital admissions are due to heart failure every year. Mean hospital stay is 11 days. More than 32,000 deaths are related to cardiac failure. Money spent for cardiac failure represents more than 1% of all medical budget.

Adult↗

PubMed2002

Time courses of apoptosis and cell proliferation and their relationship to arterial remodeling and restenosis after angioplasty in an atherosclerotic rabbit model.

OBJECTIVES: We sought to evaluate whether cellular mass changes (including apoptosis and proliferation) after arterial injury could interact with restenosis and arterial remodeling. BACKGROUND: The mechanisms controlling arterial remodeling after angioplasty remain poorly understood. Apoptosis and cell proliferation have been previously described after balloon angioplasty. However, their importance in the occurrence of arterial remodeling and restenosis is unknown. METHODS: Atherosclerosis was induced in 48 femoral arteries of New Zealand White rabbits by air-desiccation and a high-cholesterol diet. One month later, angioplasty was performed in 40 arteries. Apoptosis, cell proliferation, residual stenosis and arterial remodeling were evaluated at 2 h and 3, 7, 14, 21 and 28 days after angioplasty. RESULTS: Cell proliferation and apoptosis profiles were similar, but the peak in cell proliferation occurred approximately four days earlier than the peak in apoptosis in the neointima and media. Apoptosis density was positively correlated with arterial remodeling in the neointima and media (r = 0.69, p = 0.005 and r = 0.50, p = 0.05, respectively). Moreover, residual stenosis was inversely correlated with apoptosis density in the neointima and media (r = -0.62, p = 0.008 and r = -0.52, p = 0.04, respectively). In contrast, cell proliferation was independent of restenosis and arterial remodeling. CONCLUSIONS: In this model, cell proliferation preceded apoptosis throughout the four weeks after angioplasty. Apoptosis was inversely correlated with restenosis. Interestingly, apoptosis was also related to enlargement remodeling after balloon angioplasty.

Angioplasty, Balloon, Coronary↗

PubMedDate not supplied

Transplantation of cardiac-committed mouse embryonic stem cells to infarcted sheep myocardium: a preclinical study.

BACKGROUND: Heart failure develops after myocardial infarction and is a major cause of morbidity and mortality. The ability to direct differentiation of embryonic stem cells (ESC) towards a cardiomyogenic phenotype makes them an attractive therapeutic option for cardiac repair, but species-specific and individual-specific immunological imprinting remains a hurdle. Our aim was to ascertain whether the purported immune privilege of ESC allows for their cross-species engraftment in a clinically relevant large-animal model. METHODS: We studied engraftment and differentiation of cardiac-committed mouse ESC in 18 sheep in which a myocardial infarction had been induced; nine controls received medium and nine sheep (five of which were immunosuppressed) received ESC. The gain in myocardial function was measured by echocardiography 1 month after cell transplantation. FINDINGS: Cardiac-committed murine ESC engrafted in infarcted myocardium of immunosuppressed and immunocompetent sheep, and differentiated into mature cardiomyocytes that expressed connexins. Colonisation of the scar area by ESC was accompanied by a functional benefit of the damaged myocardium. Left-ventricular ejection fraction deteriorated in the control group by a median of 9.9% (range -20 to 0.3) relative to baseline (p=0.011) whereas in the treated group it improved by 6.6% (-5.7 to 50.8; comparison between groups p=0.002). INTERPRETATION: These findings obtained in a clinically relevant large-animal model of heart failure strengthen the potential therapeutic use of ESC to regenerate the severely dysfunctional myocardium and bring additional evidence for an immune privilege of these cells.

Animals↗