RESUMEN
Thoracic radiation therapy may result in accelerated atherosclerosis and in late aortic valve stenosis (AS). In this study, we assessed the feasibility of inducing radiation-induced AS using a targeted aortic valve irradiation (10 or 20 Grays) in two groups of C57Bl6/J (WT) and ApoE-/- mice compared to a control (no irradiation). Peak aortic jet velocity was evaluated by echocardiography to characterize AS. T2*-weighted magnetic resonance imaging after injection of MPIO-αVCAM-1 was used to examine aortic inflammation resulting from irradiation. A T2* signal void on valve leaflets and aortic sinus was considered positive. Valve remodeling and mineralization were assessed using von Kossa staining. Finally, the impact of radiation on cell viability and cycle from aortic human valvular interstitial cells (hVICs) was also assessed. The targeted aortic valve irradiation in ApoE-/- mice resulted in an AS characterized by an increase in peak aortic jet velocity associated with valve leaflet and aortic sinus remodeling, including mineralization process, at the 3-month follow-up. There was a linear correlation between histological findings and peak aortic jet velocity (r = 0.57, p < 0.01). In addition, irradiation was associated with aortic root inflammation, evidenced by molecular MR imaging (p < 0.01). No significant effect of radiation exposure was detected on WT animals. Radiation exposure did not affect hVICs viability and cell cycle. We conclude that targeted radiation exposure of the aortic valve in mice results in ApoE-/-, but not in WT, mice in an aortic valve remodeling mimicking the human lesions. This preclinical model could be a useful tool for future assessment of therapeutic interventions.
RESUMEN
Many studies pointed out the deleterious effects of high temperatures events during the crop reproductive phase on seed yield and quality. However, plant responses to repeated stressing events remain poorly understood, while the increased frequency of extreme abiotic constraints, such as spring and summer heat waves, has been proven as one feature of the on-going and future climate change. The responses of oilseed rape plants subjected to three heat stress sequences that differed in the intensity, the timing of application, the duration and the frequency of the high temperature events were investigated throughout the seed development and maturation phases under controlled conditions. Seed yield and components were measured in three different harvest dates. Biochemical and histological analyses of seeds were carried out in order to monitor the evolution of the main storage compounds (fatty acids, proteins, sugars) involved in seed nutritional quality. Although the effects of heat stress were not significant on total yield, differences in seed number and weight highlighted the strong compensation capacity in indeterminate growth species. Heat stress induced significant decreases and increases in seed oil and protein content respectively, to different extent according to the age of the pods. Soluble sugars concentrations were impacted by heat during seed development, but not when the seeds reached physiological maturity, thus indicating compensatory mechanisms that set up after the stress exposure. Our results led to conclude that the effects of repeated heat stresses on seed yield and quality were tightly related to (i) the optimal temperature of a given compound biosynthesis process, and (ii) the synchrony between the temperature event and the period of biosynthesis of the targeted storage compound. These results highlight the complexity to design thermo-sensitizing protocols to maintain or even improve the various seed quality related criteria, especially in species with indeterminate growth.
