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Saint-Herblain, France

Cariou B.,Nantes University Hospital Center | Cariou B.,LInstitut du Thorax
Diabetes and Metabolism | Year: 2012

The management of type 2 diabetes continues to evolve as new data emerge. Although glycaemic control is still important, other risk factors - such as hypertension, dyslipidaemia and obesity - must also be addressed in order to reduce the long-term risks of cardiovascular complications and mortality. In this context, targeting the incretin system, and glucagon-like peptide-1 (GLP-1) in particular, has generated much interest. GLP-1 is released from the gut in response to food ingestion and plays a crucial role in glucose homeostasis. GLP-1 receptors are expressed in the heart and vasculature, prompting evaluation of their physiological role and pharmacological stimulation, both in healthy and disease states. These studies indicate that GLP-1 and GLP-1-based therapies appear to have direct, beneficial effects on the cardiovascular system, in addition to their glucose-lowering properties, such as modulation of blood pressure, endothelial function, and myocardial contractility. Intriguingly, some of these effects appear to be independent of GLP-1 receptor signalling. Data from clinical studies of the GLP-1 receptor agonists, exenatide and liraglutide on cardiovascular risk factors, in patients with type 2 diabetes are also promising and the results from prospective studies to assess cardiovascular outcomes are eagerly awaited. © 2012 Elsevier Masson SAS.

Obadia J.-F.,Service de Chirurgie Cardiothoracique et Transplantation | Obadia J.-F.,French Institute of Health and Medical Research | Armoiry X.,Hospices Civils de Lyon | Armoiry X.,University Claude Bernard Lyon 1 | And 15 more authors.
EuroIntervention | Year: 2015

Aims: Percutaneous mitral valve repair (pMVR) is a new therapeutic option for mitral valve regurgitation. Positive preliminary results in non-randomised studies have been published supporting the use of the MitraClip system in patients with secondary mitral regurgitation (MR) and poor left ventricular (LV) function contraindicated to surgery. The aim of the MITRA-FR study is to provide a higher level of evidence for the efficacy of the MitraClip device in this setting. Methods and results: The MITRA-FR study is a national, multicentre, investigator-initiated, open-label, randomised trial to evaluate the benefits and safety of pMVR using the MitraClip system plus optimal medical therapy (OMT) compared with OMT alone (control) in patients with severe symptomatic secondary MR contraindicated to surgical repair. The trial aims to enrol 144 MitraClip-treated subjects and 144 control (OMT alone) patients. The primary endpoint is a composite of all-cause mortality and unplanned hospitalisations for heart failure at 12 months after randomisation. Conclusions: MITRA-FR is a randomised controlled national trial designed to evaluate the performance of pMVR in comparison to OMT in patients with severe symptomatic secondary MR contraindicated to cardiac surgery. © Europa Digital & Publishing 2015. All rights reserved.

Oskouei B.N.,University of Miami | Lamirault G.,LInstitut du Thorax | Joseph C.,University of Miami | Treuer A.V.,University of Miami | And 7 more authors.
Stem Cells Translational Medicine | Year: 2012

Whereas cardiac-derived c-kit+ stem cells (CSCs) and bone marrow-derived mesenchymal stem cells (MSCs) are undergoing clinical trials testing safety and efficacy as a cell-based therapy, the relative therapeutic and biologic efficacy of these two cell types is unknown. We hypothesized that human CSCs have greater ability than MSCs to engraft, differentiate, and improve cardiac function. We compared intramyocardial injection of human fetal CSCs (36,000) with two doses of adult MSCs (36,000 and 1,000,000) or control (phosphate buffered saline) in nonobese diabetic/severe combined immune deficiency mice after coronary artery ligation. The myocardial infarction-induced enlargement in left ventricular chamber dimensions was ameliorated by CSCs (p <.05 for diastolic and systolic volumes), as was the decline in ejection fraction (EF; p <.05). Whereas 1 × 106 MSCs partially ameliorated ventricular remodeling and improved EF to a similar degree as CSCs, 36,000 MSCs did not influence chamber architecture or function. All cell therapies improved myocardial contractility, but CSCs preferentially reduced scar size and reduced vascular afterload. Engraftment and trilineage differentiation was substantially greater with CSCs than with MSCs. Adult-cultured c-kit+ CSCs were less effective than fetal, but were still more potent than high-dose MSCs. These data demonstrate enhanced CSC engraftment, differentiation, and improved cardiac remodeling and function in ischemic heart failure. MSCs required a 30-fold greater dose than CSCs to improve cardiac function and anatomy. Together, these findings demonstrate a greater potency of CSCs than bone marrow MSCs in cardiac repair. ©AlphaMed Press.

Cariou B.,LInstitut du Thorax | Cariou B.,French Institute of Health and Medical Research
Medecine des Maladies Metaboliques | Year: 2015

Statins are the most widely used lipid lowering drugs due to their proven efficacy to reduce cardiovascular events. Recent post-hoc analyses of randomized controlled trials demonstrated that statins are associated with an increased risk of developing type 2 diabetes (T2D). The risk is higher with high doses of statins and in people with preexisting risk factors for T2D. Whether some statins are more diabetogenic than others remains a controversial issue. The underlying molecular mechanisms sustaining the diabetogenic action of statins remains largely unknown. From a clinical perspective, evidence suggest that the benefits of statins for the reduction of cardiovascular risk far outweigh the risk of developing T2D, especially in patients with higher cardiovascular risk. However, physicians should assess all patients for their T2D risk prior to starting statin therapy in order to reinforce lifestyle changes and to monitor glycemic parameters. © 2014-Elsevier Masson SAS-Tous droits réservés.

Cariou B.,LInstitut du Thorax | Cariou B.,French Institute of Health and Medical Research
Medecine des Maladies Metaboliques | Year: 2015

Tyrosine kinase inhibitors (TKIs) are targeted therapies which are widely used in clinical oncology. TKIs target common mechanisms of growth, invasion, metastasis, and angiogenesis. However, many TKls are nonselective and their use is associated with important side effects, especially endocrine-related side effects. Consistent data indicate that TKIs influence glucose metabolism. Surprisingly, both increased and decreased plasma glucose levels have been attributed to TKIs. Thus, it is actually recommended to monitor HbA1c and blood glucose levels periodically in patients treated with TKIs. © 2014-Elsevier Masson SAS-Tous droits réservés.

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