European journal of clinical investigation
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The concept of developmental origins of health and disease (DOHaD) was initially supported by the low birth weight and higher risk of developing cardiovascular disease in adult life, caused by nutrition restriction during foetal development. However, other programming windows have been recognized in the last years, namely lactation, infancy, adolescence and even preconception. ⋯ The impact of maternal obesity and obesogenic diets in milk quality is discussed, including the alterations in specific micro and macronutrients, as well as the impact of such alterations in the development of metabolic syndrome-associated features in the newborn, such as insulin resistance and adiposity. Moreover, the impact of milk quality and formula feeding in infants' gut microbiota, immune system maturation and in the nutrient-sensing mechanisms, namely those related to gut hormones and leptin, are also discussed under the current knowledge.
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Eur. J. Clin. Invest. · May 2021
ReviewUpdating concepts on atherosclerotic inflammation: from pathophysiology to treatment.
Atherosclerosis is recognized as a systemic low-grade inflammatory disease. Furthermore, the dysregulation of the inflammatory response and its timely resolution is a pivotal process in determining the clinical manifestations of cardiac and cerebral acute ischaemia following atherothrombosis. ⋯ Although a large amount of evidence from animal models of atherothrombotic disease, and promising results of clinical trials, anti-inflammatory treatments against atherosclerosis are not yet recommended. A deepest understanding of pathophysiological mechanisms underlying the mechanisms driving resolution of the acute inflammation will probably allow to identify the optimal molecular target.
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Eur. J. Clin. Invest. · May 2021
ReviewThe long and winding road to target protein misfolding in cardiovascular diseases.
In the last decades, cardiovascular diseases (CVD) have remained the first leading cause of mortality and morbidity in the world. Although several therapeutic approaches have been introduced in the past, the development of novel treatments remains an important research goal, which is hampered by the lack of understanding of key mechanisms and targets. Emerging evidences in recent years indicate the involvement of misfolded proteins aggregation and the derailment of protein quality control in the pathogenesis of cardiovascular diseases. Several potential interventions targeting protein quality control have been translated from the bench to the bedside to effectively employ the misfolded proteins as promising therapeutic targets for cardiac diseases, but with trivial results. ⋯ At present, no therapeutic strategies have been reported to attenuate proteotoxicity in patients with CVD due to a lack of specific biomarkers for pinpointing upstream events in protein folding defects at a subclinical stage of the diseases requiring an intensive collaboration between basic scientists and clinicians.
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Eur. J. Clin. Invest. · May 2021
Vascular endothelial growth factor on Runt-related transcript factor-2 in aortic valve cells.
Calcific aortic valve disease is associated with ageing and high mortality. However, no effective pharmacological treatment has been developed. Vascular endothelial growth factor (VEGF) and its receptor are overexpressed in the calcified aortic valve tissue. However, the role of VEGF in calcific aortic valve disease pathogenesis and its underlying mechanisms remain unclear. ⋯ VEGF upregulated Runt-related transcription factor 2 expression in VICs by activating the IP3R/CaMKII/CREB signalling pathway.
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Eur. J. Clin. Invest. · May 2021
Erythrocyte membrane fluidity as a marker of diabetic retinopathy in type 1 diabetes mellitus.
A high level of glycosylated haemoglobin (HbA1c), which is a nonenzymatic glycosylation product, is correlated with an increased risk of developing microangiopathic complications in Diabetes Mellitus (DM). Erythrocyte membrane fluidity could provide a complementary index to monitor the development of complications since it is influenced by several hyperglycaemia-induced pathways and other independent risk factors. ⋯ Altered erythrocyte membrane fluidity may therefore represent a marker of retinopathy in T1DM patients as a result of post-translational modifications of multifactorial aetiology (nonenzymatic glycosylation of proteins, generation of reactive oxygen species, lipid peroxidation).