Browsing by Author "Zamorano, Jose Luis"
Now showing 1 - 6 of 6
- Results Per Page
- Sort Options
Item Nanotecnología aplicada a conservar la matriz extracelular como herramienta teranóstica en el infarto agudo de miocardio.(Revista Española de Cardiología, 2019) Ramírez Carracedo, Rafael; Díez, Javier; Sanmartín; Saura, Marta; Zamorano, Jose Luis; Zaragoza Sánchez, CarlosItem New environmental factors related to diabetes risk in humans: Emerging bisphenols used in synthesis of plastics.(World Journal of Diabetes, 2023) Moreno-Gómez-Toledano, Rafael; Delgado-Marín, María; Cook-Calvete, Alberto; González-Cucharero, Claudia; Alcharani, Nunzio; Jiménez-Guirado, Beatriz; Hernandez, Ignacio; Ramírez Carracedo, Rafael; Tesoro Santos, Laura; Botana, Laura; Sánchez-Esteban, Sandra; Diez-Mata, Javier; Zamorano, Jose Luis; Bosch, Ricardo J.; Zaragoza Sánchez, Carlos; Saura Redondo, MartaBACKGROUND Diabetes mellitus (DM) is one of the largest global health emergencies of the 21st century. In recent years, its connection with environmental pollutants, such as bisphenol A (BPA), has been demonstrated; consequently, new structurally similar molecules are used to replace BPA in the plastics industry (BPS, BPF and BPAF). AIM To carry out a systematic review to allow coherent evaluation of the state of the art. Subsequently, a meta-analysis was performed to unify the existing quantitative data. METHODS Firstly, a systematic review was carried out, using the terms “(bisphenol) AND (Diabetes OR Hyperglycemia)”, to maximize the number of results. Subsequently, three authors analyzed the set of articles. Finally, a meta-analysis was performed for each BP, using RevMan software. In addition, funnel plots were developed to study publication bias. RESULTS The systematic analysis of the literature revealed 13 recent articles (2017–2023) related to the study paradigm. The qualitative analysis showed interesting data linking diabetes to the three most widely used substitute BPs in the industry: BPS, BPF and BPAF. Finally, the meta-analysis determined a positive relationship with BPS, BPF and BPAF, which was only statistically significant with BPS. CONCLUSION There is a need to apply the precautionary principle, regulating the use of new BPs. Therefore, replacing BPA with BPS, BPF or BPAF is unlikely to protect the population from potential health risks, such as DMItem NIL10: A New IL10-Receptor Binding Nanoparticle That Induces Cardiac Protection in Mice and Pigs Subjected to Acute Myocardial Infarction through STAT3/NF-kB Activation.(Pharmaceutics, 2022) Tesoro Santos, Laura; Hernández, Ignacio; Ramírez Carracedo, Rafael; Díez-Mata, Javier; Alcharani, Nunzio; Jiménez-Guirado, Beatriz; Ovejero-Paredes, Karina; Filice, Marco; Zamorano, Jose Luis; Saura, Marta; Zaragoza Sánchez, Carlos; Botana, LauraBackground: Early response after acute myocardial infarction (AMI) prevents extensive cardiac necrosis, in which inflammation resolution, including expression of anti-inflammatory interleukin-10 (IL-10), may play a key role. (2) Methods: We synthesized NIL10, a micelle-based nanoparticle, to target IL-10 receptor in mice and pigs subjected to AMI. (3) Results: Administration of NIL10 induced cardiac protection of wild-type and IL-10 knockout mice and pigs subjected to AMI. Cardiac protection was not induced in IL-10-receptor null mice, as shown by a significant recovery of cardiac function, in which inflammatory foci and fibrosis were strongly reduced, together with the finding that resolving M2-like macrophage populations were increased after day 3 of reperfusion. In addition, anti-inflammatory cytokines, including IL-4, IL-7, IL-10, IL-13, IL-16, and IL-27 were also elevated. Mechanistically, NIL10 induced activation of the IL-10 receptor/STAT-3 signaling pathway, and STAT3-dependent inhibition of nuclear translocation of pro-inflammatory NF-kB transcription factor. (4) Conclusions: Taken together, we propose using NIL10 as a novel therapeutic tool against AMI-induced cardiac damageItem Nitric Oxide Induces Cardiac Protection by Preventing Extracellular Matrix Degradation through the Complex Caveolin-3/EMMPRIN in Cardiac Myocytes.(PLOS One, 2016-09-20) Cuadrado, Irene; Castejón, Borja; Martín, Ana M.; Saura, Marta; Reventun-Torralba, Paula; Zamorano, Jose Luis; Zaragoza Sánchez, CarlosInhibition of Extracellular Matrix degradation by nitric oxide (NO) induces cardiac protection against coronary ischemia/reperfusion (IR). Glycosylation of Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) stimulates enzymatic activation of matrix metalloproteinases (MMPs) in the heart, although the mechanisms leading to EMMPRIN glycosylation are poorly understood.We sought to determine if NO may induce cardiac protection by preventing glycosylation of EMMPRIN in a mouse model of IR. Here we found that Caveolin-3 binds to low glycosylated EMMPRIN (LG-EMMPRIN) in cardiac cells and in the hearts of healthy mice, whereas IR disrupted the complex in nitric oxide synthase 2 (NOS2) knockout (KO) mice. By contrast, the binding was partially restored when mice were fed with an NO donor (DEA-NO) in the drinkingwater, showing a significant reduction on infarct size (NOS2KO: 34.6±5 vs NOS2KO+DEA-NO: 20.7±9), in expression of matrix metalloproteinases, and cardiac performancewas improved (left ventricular ejection fraction (LVEF). NOS2KO: 31±4 vs NOS2KO+DEA-NO: 46±6). The role of Caveolin-3/EMMPRIN in NOmediated cardiac protectionwas further assayed in Caveolin-3 KO mice, showing no significant improvement on infarct size (Caveolin-3 KO: 34.8±3 vs Caveolin-3 KO+DEA-NO:33.7 ±5), or in the expression of MMPs, suggesting that stabilization of the complex Caveolin-3/ LG-EMMPRIN may play a significant role in the cardioprotective effect of NO against IR.Item Preclinical models of atherosclerosis. The future of Hybrid PET/MR technology for the early detection of vulnerable plaque.(Expert Reviews in Molecular Medicine, 2016) Cuadrado, Irene; Saura, Marta; Castejón, Borja; Martín, Ana María; Herruzo Priego, Irene; Balatsos, Nikolas; Zamorano, Jose Luis; Zaragoza Sánchez, CarlosCardiovascular diseases are the leading cause of death in developed countries. The aetiology is currently multifactorial, thus making them very difficult to prevent. Preclinical models of atherothrombotic diseases, including vulnerable plaque-associated complications, are now providing significant insights into pathologies like atherosclerosis, and in combination with the most recent advances in new non-invasive imaging technologies, they have become essential tools to evaluate new therapeutic strategies, with which can forecast and prevent plaque rupture. Positron emission tomography (PET)/computed tomography imaging is currently used for plaque visualisation in clinical and pre-clinical cardiovascular research, albeit with significant limitations. However, the combination of PET and magnetic resonance imaging (MRI) technologies is still the best option available today, as combined PET/MRI scans provide simultaneous data acquisition together with high quality anatomical information, sensitivity and lower radiation exposure for the patient. The coming years may represent a new era for the implementation of PET/MRI in clinical practice, but first, clinically efficient attenuation correction algorithms and research towards multimodal reagents and safety issues should be validated at the preclinical level.Item Theranostic Contribution of Extracellular Matrix Metalloprotease Inducer-Paramagnetic Nanoparticles Against Acute Myocardial Infarction in a Pig Model of Coronary Ischemia- Reperfusion.(Circulation: cardiovascular imaging, 2022) Ramírez Carracedo, Rafael; Sanmartin, Marcelo; Ten, Amadeo; Hernandez, Ignacio; Tesoro Santos, Laura; Diez-Mata, Javier; Botana, Laura; Ovejero-Paredes, Karina; Filice, Marco; Alberich-Bayarri, Angel; Martí-Bonmatí, Luis; Largo-Aramburu, Carlota; Saura, Marta; Zamorano, Jose Luis; Zaragoza Sánchez, CarlosBACKGROUND: Rapid screening and accurate diagnosis of acute myocardial infarction are critical to reduce the progression of myocardial necrosis, in which proteolytic degradation of myocardial extracellular matrix plays a major role. In previous studies, we found that targeting the extracellular matrix metalloprotease inducer (EMMPRIN) by injecting nanoparticles conjugated with the specific EMMPRIN-binding peptide AP9 significantly improved cardiac function in mice subjected to ischemia/reperfusion. METHODS: In a porcine model of coronary ischemia/reperfusion, we tested the theragnostic effects of administering 0.1 mg/kg gadolinium-containing nanoparticles conjugated with AP9 (NAP9), a synthetic peptide that targets EMMPRIN or a control nanoparticle (NAPSC). Cardiac magnetic resonance assessment of the infarct progression, ventricular function, and nanoparticle distribution was performed the next 7 days. We also measured the infarcted area of the heart and cardiac remodeling at 7 or 21 days after ischemia/reperfusion. RESULTS: After 21 days of ischemia/reperfusion, NAP9 reduced the extension of cardiac necrosis (14.1±9.7 versus 35.5±1.8) and the levels of collagenolytic activity of MMPs (matrix metalloproteases), along with a significant reduction in collagen deposition (7.5±4.5 versus 41.3±20); including the ratio of type I versus III collagen fibers in the necrotic myocardium. In terms of cardiac function, the response to NAP9 administration resulted in a significant improvement of cardiac performance overtime, as evidenced by the left ventricle ejection fraction (64.0±7.8), when compared with those present in the NAPSC group (47.3±4.7). As shown by magnetic resonance imaging, noninvasive molecular imaging of NAP9 enabled us to find a significant reduction in cardiac necrosis, myocardial edema, hemorrhage, and microvascular obstruction, suggesting that NAP9 may reduce myocardial injury and preserve left ventricular function, at least, by preventing the effect of EMMPRIN on extracellular matrix degradation. CONCLUSIONS: Our data point towards NAP9 as a promising theragnostic tool in managing acute myocardial infarction, by inhibiting EMMPRIN-induced extracellular matrix degradation and allowing noninvasive visualization of cardiac necrosis progression over time.