Personne : Charbonneau, Éric
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Charbonneau
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Éric
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Université Laval. Département de chirurgie
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ncf11892594
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Publication Restreint Downregulation of microRNA-126 contributes to the failing right ventricle in pulmonary arterial hypertension(American Heart Association, 2015-09-08) Dahou, Abdellaziz; Charbonneau, Éric; Provencher, Steeve; Thébault, Christophe; Ruffenach, Grégoire; Breuils-Bonnet, Sandra; Bonnet, Sébastien; Johnson, Ian; Perron, Jean; Paulin, Roxane; Tremblay, Ève; Wong, Ryan; Lajoie, Annie C.; Joubert, Philippe; Potus, François; Pibarot, Philippe; Michelakis, Evangelos D.; Graydon, Colin; Paradis, Renée; Nadeau, ValérieBackground—Right ventricular (RV) failure is the most important factor of both morbidity and mortality in pulmonary arterial hypertension (PAH). However, the underlying mechanisms resulting in the failed RV in PAH remain unknown. There is growing evidence that angiogenesis and microRNAs are involved in PAH-associated RV failure. We hypothesized that microRNA-126 (miR-126) downregulation decreases microvessel density and promotes the transition from a compensated to a decompensated RV in PAH. Methods and Results—We studied RV free wall tissues from humans with normal RV (n=17), those with compensated RV hypertrophy (n=8), and patients with PAH with decompensated RV failure (n=14). Compared with RV tissues from patients with compensated RV hypertrophy, patients with decompensated RV failure had decreased miR-126 expression (quantitative reverse transcription–polymerase chain reaction; P<0.01) and capillary density (CD31+ immunofluorescence; P<0.001), whereas left ventricular tissues were not affected. miR-126 downregulation was associated with increased Sprouty-related EVH1 domain-containing protein 1 (SPRED-1), leading to decreased activation of RAF (phosphorylated RAF/RAF) and mitogen-activated protein kinase (MAPK); (phosphorylated MAPK/MAPK), thus inhibiting the vascular endothelial growth factor pathway. In vitro, Matrigel assay showed that miR-126 upregulation increased angiogenesis of primary cultured endothelial cells from patients with decompensated RV failure. Furthermore, in vivo miR-126 upregulation (mimic intravenous injection) improved cardiac vascular density and function of monocrotaline-induced PAH animals. Conclusions—RV failure in PAH is associated with a specific molecular signature within the RV, contributing to a decrease in RV vascular density and promoting the progression to RV failure. More importantly, miR-126 upregulation in the RV improves microvessel density and RV function in experimental PAH.Publication Accès libre Impact of aortic stenosis severity and its interaction with prosthesis-patient mismatch on operative mortality following aortic valve replacement.(ICR, 2012-03-02) Girerd, Nicolas; Charbonneau, Éric; Dumont, Éric; Magne, Julien; Baillot, Richard; Voisine, Pierre; Pibarot, Philippe; Dumesnil, Jean G.; Dagenais, François; Mathieu, PatrickThe optimal timing of aortic valve replacement (AVR) in patients with severe aortic stenosis (AS) is a source of debate. Moreover, it has been shown previously that prosthesis-patient mismatch (PPM) is an independent predictor of operative mortality after AVR. The study aim was to assess the effect of the preoperative severity of AS and its interaction with PPM with respect to operative mortality after AVR.Publication Restreint The impact of complete revascularization on long-term survival is strongly dependent on age(Little, Brown & Co., 2012-11-01) Charbonneau, Éric; Dumont, Éric; Magne, Julien; Baillot, Richard; Voisine, Pierre; Mohammadi, Siamak; Doyle, Daniel; Girerd, Nicolas; Pibarot, Philippe; Dagenais, François; Rabilloud, Muriel; Mathieu, PatrickBACKGROUND: Complete revascularization during coronary artery bypass grafting (CABG) has been reported to be associated with better short-term and long-term outcomes. We hypothesized that the survival benefit of complete revascularization would be less in old patients than in young patients. METHODS: We analyzed data from 6,539 consecutive patients who had undergone a first isolated on-pump CABG procedure between 2000 and 2008. We investigated the impact of complete revascularization and its interaction with age on operative and long-term survival using propensity-score-based analyses. RESULTS: Patients with incomplete (versus complete) revascularization (n=318 [4.9%]) were sicker overall. During a mean follow-up of 5.8±2.2 years, 909 patients died. In the propensity-score-matched analysis, operative mortality was not significantly different between patients with complete revascularization and those with incomplete revascularization (1.9% versus 2.8%; odds ratio [OR], 1.46; 95% confidence interval [CI], 0.56-3.46; p=0.48). In contrast, incomplete revascularization had an independent negative impact on long-term survival, which was strongly age dependent (hazard ratio [HR] for interaction, 0.96 per year increment; p=0.02). In a propensity-score-matched analysis, incomplete revascularization was independently associated with higher long-term mortality in patients younger than 60 years (HR, 3.27; 95% CI, 1.21-8.86; p=0.02), whereas it was not in patients 60 to 70 years and 70 years of age and older (p=0.87 and p=0.24, respectively). CONCLUSIONS: Contrary to what is observed in patients younger than 60 years, complete revascularization does not seem to improve long-term survival in older patients. This suggests that elderly patients at high operative risk may be considered, when deemed clinically appropriate, for limited coronary revascularization