Nabil Nicolas Temporary Lecturer and Research Assistant at Bordeaux University/Inserm U1034 Research Laboratory
Course and current status
- Internship in INSERM U1034 Laboratory - Biology of Cardiovascular Diseases
- Worked on the subject : "3D characterization of the coronary network's architecture in Heart Failure with preserved Ejection Fraction"
- Internship in INSERM U1034 Laboratory - Biology of Cardiovascular Diseases
- Worked on the subject : "3D quantitative analysis of mice renal artery network's architecture"
Scientific summary
Heart Failure with preserved Ejection Fraction (HFpEF) is a cardiovascular disease characterized by telediastolic dysfunction, diastolic left ventricular stiffness, and myocardial concentric remodeling. It represents 50% of the heart failure cases with nearly 65 million cases worldwide. Main risks factors include advanced age (> 67 years old), sex (women being more susceptible to develop the disease), and several comorbidities, in particular obesity and diabetes. Even though there is a protocol for the diagnosis of the disease from clinical signs, its treatment remains inefficient.
The etiology of HF-pEF is poorly understood. However, it has been shown to be associated with the rarefaction of the coronary microvasculature (vessel diameter <100-150µm), and there is an emerging paradigm that comorbidities contribute to the development of the disease via a systemic proinflammatory state leading to coronary endothelial dysfunction. On the other hand, it is well established that fluid shear stress (FSS) sensing by the endothelial cells (ECs) plays a key role in vascular morphogenesis and remodeling. However, little attention has been paid to the possible contribution of FSS in the development of HFpEF.
Our physiopathological hypothesis is that risk factors of HFpEF, primarily obesity and types 2 diabetes, generate a systemic inflammation that induces vessel endothelial dysfunction, in particular, alteration of FSS sensing by the coronary ECs, inducing the disruption of the dynamical homeostasis of the vascular architecture, leading to pathological topological reorganization and functional loss of the coronary microvasculature.
The investigation will be done at different levels of integration, including the behavior and signaling pathways of ECs, the structural and functional properties of the whole organ, and the functional properties of the cardiovascular system on the organism.
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Articles:
1-Nicolas, N., Roux, E., 2021. 3D Imaging and Quantitative Characterization of Mouse Capillary Coronary Network Architecture. Biology 10, 306. https://doi.org/10.3390/biology10040306
2-Nicolas, Nabil, Nicolas, Nour, Roux, E., 2021. Computational Identification and 3D Morphological Characterization of Renal Glomeruli in Optically Cleared Murine Kidneys. Sensors 21, 7440. https://doi.org/10.3390/s21227440
3-Nicolas, N.; Dinet, V.; Roux, E. 3D Imaging and Morphometric Descriptors of Vascular Networks on Optically Cleared Organs. iScience 2023, 26, 108007, doi:10.1016/j.isci.2023.108007.
