The studies published by the CNIC scientists during the year 2017 consolidate this center as an institution of Spanish and international research excellence, highlighting mainly the work on cardiovascular diseases, immunity, cancer, metabolism and pharmacological toxicity.
Analysis of gene function
The team of Dr. Rui Benedito has developed a new technology that allows defining the function and interaction of genes with a high spatio-temporal resolution, both during development and in pathological situations. This method will contribute to increase knowledge about how the genome operates in the different cell types of which the human organism is composed and to better understand the networks of gene interaction and the hierarchies that regulate them.
Identification of new pharmacological toxicities
Following the recent designation of inhibitors of the kinase Plk1 by the FDA as an innovative therapy in leukemia, the team of Juan Miguel Redondo has collaborated in a research that reveals a previously unknown cardiovascular toxicity, associated with the prolonged use of this group of drugs. The study demonstrates the occurrence of cardiovascular defects in mice in which the activity of Plk1 is diminished as a consequence of treatment with volasertib. Although the drug does not cause defects in the growth of mice with low levels of Plk1, it does lead to arterial rupture and secondary cardiovascular effects, indicating that the arteries are more sensitive to the inhibition of Plk1 than other adult tissues. The same study shows that Plk1 is essential in the contraction of the arterial wall cells, a key process in maintaining an appropriate blood pressure.
Prevention and reversal of the aneurysm
In the study led by Miguel Campanero and Juan Miguel Redondo, two potential molecular targets have been identified to treat or even prevent aortic aneurysm, a pathological thickening of the arterial wall that usually has a fatal outcome. Using animal models of different types of aneurysm, including that associated with Marfan syndrome, it has been discovered that mice deficient in metalloproteinase ADAMTS1 develop a pathology similar to that of this syndrome. In these animals, the inactivation of inducible synthase of nitric oxide (siNO2), located in cells of the arterial wall, prevents the disease in this and in other aneurysm models. The study also demonstrates that the suppression of nitric oxide production through the pharmacological inhibition of siNO2 rapidly and effectively reverses arterial dilation and deterioration of the medial layer of the aorta, both in mice with Marfan syndrome and in deficient in ADAMTS1. Two important aspects of this study are, on the one hand, the demonstration of the curative potential of this approach and, on the other, the confirmation that it is equally effective, regardless of the age of the mice with SMf. This last aspect would indicate that siNO2 is essential both for the onset and for the progression of the disease.
Although there are differences between animal models and human disease, the magnitude of the pharmacological effect would justify the initiation of the pre-clinical and clinical development of the siNO2 inhibitors for this indication.
Breakfast in cardiovascular prevention
Skipping breakfast or eating too little at the beginning of the day doubles the risk of atherosclerosis, according to a study in which CNIC researchers have collaborated. The findings show the advantage of eating a breakfast of high energy content compared to one containing less than 5% of the total daily calories recommended, which would be equivalent to a breakfast of 100 calories in a diet of 2000 calories a day. The increase in the number of atherosclerotic lesions observed in the latter group was shown to be independent of the classic risk factors, such as smoking, high cholesterol or physical inactivity. The researchers in this study also deduce that skipping breakfast could be a marker of unhealthy eating habits and lifestyle.
Improvement in the prediction of cardiovascular risk
The research conducted by the team of Dr. Valentín Fuster places in a preferential position three-dimensional ultrasonography in the identification of individuals at risk of developing cardiovascular diseases. In the examination of almost 4000 asymptomatic people of mature age and without circulatory history, it was determined that the total atherosclerotic load is a highly useful parameter in the stratification of individual cardiovascular risk, when considered together with the classic risk factors, such as cholesterol, smoking. , blood pressure, diabetes, obesity and exercise. The results also indicate that the atherosclerotic load is twice as high in men as in women and that it increases with age, being located mainly in the femoral artery. Although this technology is still under development, it allows to estimate the volume of the plates with greater reliability than traditional two-dimensional techniques.
The same research group has also improved the prediction of atherosclerosis in individuals without risk factors, emphasizing the need for an aggressive reduction of LDL cholesterol. This new finding is derived from the sub-analysis of the PESA clinical trial, in which the most innovative non-invasive vascular imaging techniques have been used, with the aim of elucidating how and when cardiovascular disease begins and what has to happen to make it manifest clinically An additional study in this field has identified in the blood pressure, physical activity, fruit and vegetable intake, body mass index and smoking degree the 5 essential markers in the prediction of cardiovascular risk in healthy individuals. Called the Fuster-BEWAT index, it predicts the presence and extension of subclinical atherosclerosis in middle-aged people with no history of cardio- or cerebrovascular accidents. This index is as reliable as the one currently recommended by the American Association of Cardiology, which requires blood glucose and circulating cholesterol values.
In Distefar we echo these studies that provide key knowledge for the development of new therapies and the improvement of those already existing in various medical fields.