No abstract

Direct oral anti-coagulants (DOACs) are employed in clinical practice for the prevention and treatment of recurrent venous thromboembolism and for the prevention of stroke in non-valvular atrial fibrillation. DOACs directly and reversibly inhibit activated factor X or thrombin and can interfere with other pathophysiological processes such as inflammation, lipid metabolism, and bone turnover. We aimed to evaluate the possible effects of DOACs on osteogenesis and angiogenesis. We treated 34 patients affected by cardiovascular disorders with DOACs; biochemical and molecular analyses were performed before and after three months of treatment. Circulating progenitors (CPs; CD34−, CD45−, CD14−, CD73+, CD105+), which share typical bone marrow stem cell (MSCs) features, were harvested from peripheral blood of the study subjects to monitor the expression of osteogenesis-related genes RUNX2 and SPARC. Human umbilical vein endothelial cells (HUVECs) were used to probe angiogenesis-related VEGF, CD31, and CD105 gene expression. We performed co-culture experiments using a commercial human mesenchymal stem cells line (hMSCs) obtained from bone marrow and HUVECs. Clinical parameters related to bone metabolism, coagulation, renal and liver function, and the lipid profile were evaluated. Values of the C-terminal telopeptide type I collagen (CTX) increased after the treatment. We found a significant increase in osteogenesis marker gene expression in CPs after three months of anticoagulant therapy. An increase in the RUNX2 expression determinant alone was detected instead in hMSCs co-cultured with HUVECs in the presence of treated patients’ sera. The VEGF, CD31, and CD105 marker genes appeared to be significantly upregulated in HUVECs co-cultured with hMSCs in the presence of treated patients’ sera. Under these conditions, new vessel formation increased as well. Our results highlight an unexpected influence of DOAC therapy on osteogenic commitment and vascular endothelial function promotion.

The aim of the study was to compare the antihypertensive efficacy and safety of a new beta blocker with high beta 1 selectivity, bisoprolol, with captopril in 28 elderly patients, aged over 65 years, with mild-to-moderate essential hypertension (WHO classes I and II). After a placebo run-in period of 4 weeks, the patients were randomly allocated to receive bisoprolol (5 mg od) or captopril (25 mg bid) (double-dummy technique) for 6 weeks, according to a crossover double-blind design, with a 4-week washout period between the two active treatments. The doses were doubled after 2 weeks if the supine blood pressure was greater than 160/95 mmHg. In basal conditions and after 2, 4, and 6 weeks of each treatment, the blood pressure and heart rate were assessed both in the supine and erect positions. At the same time, the side effects and quality of life were investigated by a checklist and a self-assessment questionnaire. Standard laboratory tests and a resting ECG tracing were performed before and after each active treatment. The data from 24 patients (4 dropouts) showed a significant antihypertensive effect of both treatments (p less than 0.01) with a reduction of diastolic blood pressure to values less than or equal to 95 mmHg in 75% (18/24) of the patients treated with bisoprolol and in 83.3% (20/24) of those treated with captopril, without significant differences between the two drugs. Bisoprolol also produces a marked but symptom-free reduction of heart rate compared with captopril (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

As a result of aging, body composition changes, with a decline in muscle mass and an increase in adipose tissue (AT), which reallocates from subcutaneous to visceral depots and stores ectopically in the liver, heart and muscles. Furthermore, with aging, muscle and AT, both of which have recognized endocrine activity, become dysfunctional and contribute, in the case of positive energy balance, to the development of sarcopenic obesity (SO). SO is defined as the co-existence of excess adiposity and low muscle mass and function, and its prevalence increases with age. SO is strongly associated with greater morbidity and mortality. The pathogenesis of SO is complex and multifactorial. This review focuses mainly on the role of crosstalk between age-related dysfunctional adipose and muscle cells as one of the mechanisms leading to SO. A better understanding of this mechanisms may be useful for development of prevention strategies and treatments aimed at reducing the occurrence of SO.