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Essential Hypertension and Oxidative Stress: Novel Future Perspectives.
Franco, C, Sciatti, E, Favero, G, Bonomini, F, Vizzardi, E, Rezzani, R
International journal of molecular sciences. 2022;23(22)
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High blood pressure is one of the main risk factors for cardiovascular disease and a significant contributor to the development of strokes, heart attacks, and heart and kidney failure leading to early disability and reduced life expectancy. Essential or primary hypotension makes up 95% of high blood pressure cases, which is abnormally elevated blood pressure that is not a result of any other medical condition. Essential hypertension arises from various factors such as diet, lifestyle, environmental and genetic influences. Despite many available medications, not all patients attain well-managed blood pressure levels. Unmanaged high blood pressure can, over time, lead to narrowing and stiffening of the blood vessels and ultimately to structural and functional changes in the blood tissues. In part, this is mediated by oxidative stress, changes in antioxidant capacity and chronic low-grade inflammation, which damage the blood vessels' endothelial tissue and result in vascular stiffness. Melatonin is one of the most potent antioxidants found in nature and has been studied in short-term trials for its blood pressure lowering, antioxidant and vascular protective effects. This small open-label randomised study sought to get a better understanding of the long-term use of melatonin. Initially, the study assessed endothelial tissue damage, oxidative status and vascular stiffness in patients with high blood pressure. Subsequently, some of the participants received a low-dose melatonin supplement (1 mg/day) for one year, whilst being monitored for clinical and structural vascular changes. The study included 23 patients and 14 in the final analysis. After one year, the results showed a significant improvement in arterial stiffness in the melatonin group (11) and an improvement in endothelial tissue function, though the latter was not at statistically significant levels. Improvement in arterial stiffness seemed to be linked to a reduction in total antioxidant capacity (TAC). These findings suggest that melatonin can contribute to restoring oxidative balance in blood plasma, which reflects improved arterial stiffness. The study also demonstrated that besides being a well-tolerated intervention, melatonin also has clinical benefits even when administered at lower doses than normal.
Abstract
Among cardiovascular diseases, hypertension is one of the main risk factors predisposing to fatal complications. Oxidative stress and chronic inflammation have been identified as potentially responsible for the development of endothelial damage and vascular stiffness, two of the primum movens of hypertension and cardiovascular diseases. Based on these data, we conducted an open-label randomized study, first, to evaluate the endothelial damage and vascular stiffness in hypertense patients; second, to test the effect of supplementation with a physiological antioxidant (melatonin 1 mg/day for 1 year) in patients with essential hypertension vs. hypertensive controls. Twenty-three patients of either gender were enrolled and randomized 1:1 in two groups (control and supplemented group). The plasmatic total antioxidant capacity (as a marker of oxidative stress), blood pressure, arterial stiffness, and peripheral endothelial function were evaluated at the beginning of the study and after 1 year in both groups. Our results showed that arterial stiffness improved significantly (p = 0.022) in supplemented patients. The endothelial function increased too, even if not significantly (p = 0.688), after 1 year of melatonin administration. Moreover, the supplemented group showed a significative reduction in TAC levels (p = 0.041) correlated with the improvement of arterial stiffness. These data suggest that melatonin may play an important role in reducing the serum levels of TAC and, consequently, in improving arterial stiffness.
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A clinically meaningful metric of immune age derived from high-dimensional longitudinal monitoring.
Alpert, A, Pickman, Y, Leipold, M, Rosenberg-Hasson, Y, Ji, X, Gaujoux, R, Rabani, H, Starosvetsky, E, Kveler, K, Schaffert, S, et al
Nature medicine. 2019;25(3):487-495
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The human immune system changes with age, ultimately leading to a clinically evident, profound deterioration resulting in high morbidity and mortality rates attributed to infectious and chronic diseases. The aim of this study was to assess at high resolution the dynamics of older adults’ immune systems. The study uses multiple ‘omics’ technologies in a cohort of 135 adults (63 young adults and 72 older adults) of different ages who were sampled longitudinally over the course of 9 years to comprehensively capture population- and individual-level changes in the immune system over time. Results indicate that immune-cell frequencies changed at substantially different rates; some cell subsets show no directionality of change yet differ between young and old individuals, whereas other cell subsets continued changing (either increasing or decreasing) throughout the course of the study. Authors postulate that an individual’s immune age is a function of life history, namely environmental exposure coupled with genetic background. Thus, immune modulators may one day be identified that affect the position of an individual’s immune system along the immunological landscape.
Abstract
Immune responses generally decline with age. However, the dynamics of this process at the individual level have not been characterized, hindering quantification of an individual's immune age. Here, we use multiple 'omics' technologies to capture population- and individual-level changes in the human immune system of 135 healthy adult individuals of different ages sampled longitudinally over a nine-year period. We observed high inter-individual variability in the rates of change of cellular frequencies that was dictated by their baseline values, allowing identification of steady-state levels toward which a cell subset converged and the ordered convergence of multiple cell subsets toward an older adult homeostasis. These data form a high-dimensional trajectory of immune aging (IMM-AGE) that describes a person's immune status better than chronological age. We show that the IMM-AGE score predicted all-cause mortality beyond well-established risk factors in the Framingham Heart Study, establishing its potential use in clinics for identification of patients at risk.