Effect of Physical Exercise on the Release of Microparticles with Angiogenic Potential

Cellular communication has a fundamental role in both human physiological and pathological states and various mechanisms are involved in the crosstalk between organs. Among these, microparticles (MPs) have an important involvement. MPs are a subtype of extracellular vesicles produced by a variety of cells following activation or apoptosis. They are normally present in physiological conditions, but their concentration varies in pathological states such as cardiovascular disease, diabetes mellitus, or cancer. Acute and chronic physical exercise are able to modify MPs amounts as well. Among various actions, exercise-responsive MPs affect angiogenesis, the process through which new blood vessels grow from pre-existing vessels. Usually, the neo vascular growth has functional role; but an aberrant neovascularization accompanies several oncogenic, ischemic, or inflammatory diseases. In addition, angiogenesis is one of the key adaptations to physical exercise and training. In the present review, we report evidence regarding the effect of various typologies of exercise on circulating MPs that are able to affect angiogenesis

Nordic walking increases circulating VEGF more than traditional walking training in postmenopause.

OBJECTIVES Nordic walking (NW) is widely practiced by postmenopausal women. Its effects are peculiar owing to the involvement of more muscle groups than in traditional walking training (WT). Since mechanical load promotes secretion of vascular endothelial growth factor (VEGF) from both skeletal muscle and muscle endothelium, the aim of the study was to compare the effect of NW and WT on VEGF levels. METHOD Thirty postmenopausal women were randomly assigned to NW or WT. Both groups trained 40-50 min/day, three times per week, at a mean intensity of 12 on a 15-category scale of the ratings of perceived exertion. Since VEGF is also released from adipocytes, anthropometric parameters were assessed. RESULTS NW increased circulating VEGF more than WT (p = 0.041). Furthermore, both study groups exhibited an average decrease in weight (p = 0.023), body mass index (p = 0.024), hip circumference (p = 0.001), and arm fat index, although WT participants had higher values for this index at baseline (p < 0.001) and thus exhibited a greater net decrease compared with the NW participants (p < 0.011). CONCLUSIONS These data imply that NW increases the level of circulating VEGF more than does traditional walking when the intensity of training is equivalent

Can off-training physical behaviors influence recovery in athletes? A sccoping review

Recently, the attention on recovery in sport increased enormously although there is lack of scientific evidence on the role of lifestyle in terms of movement [i.e., physical behaviors (PBs)], apart from sleep. Few studies assessed physical activity (PA) and sedentary behavior (SB) in athletes. The aims of this scoping review were to answer to the following scientific questions: (1) How active/inactive are competitive athletes out of training? (2) Do off-training PBs affect recovery, performance, and health? (3) What strategies can be implemented to improve recovery using off-training PBs, apart from sleep? From 1,116 potentially relevant articles, nine were eligible for inclusion in this review. The main issues identified were related to the heterogeneity concerning the types of sports, age category, gender, competitive level, sample size, and instruments/devices adopted, the paucity of studies investigating the effects of PBs while awake on recovery, and the lack of experimental designs manipulating PBs while awake to accelerate recovery. Furthermore, PA and SB domains were rarely investigated, while no research articles focused on the combined effect of 24-h PBs. Eight out of nine studies measured PA, seven SB, and two included sleep. Three studies included training practice into PA measurement by the means of accelerometry. Overall, almost the totality of the athletes achieved recommended PA levels although they sustained prolonged SB. In conclusion, more descriptive researches are needed in different athletic populations and settings. Furthermore, experimental designs aimed at investigating the effects of PBs manipulation on recovery and the putative mechanisms are encouraged

Phenotypic Definition of the Progenitor Cells with Erythroid Differentiation Potential Present in Human Adult Blood

In Human Erythroid Massive Amplification (HEMA) cultures, AB mononuclear cells (MNC) generate 1-log more erythroid cells (EBs) than the corresponding CD34pos cells, suggesting that MNC may also contain CD34neg HPC. To clarify the phenotype of AB HPC which generate EBs in these cultures, flow cytometric profiling for CD34/CD36 expression, followed by isolation and functional characterization (colony-forming-ability in semisolid-media and fold-increase in HEMA) were performed. Four populations with erythroid differentiation potential were identified: CD34posCD36neg (0.1%); CD34posCD36pos (barely detectable-0.1%); CD34negCD36low (2%) and CD34negCD36neg (75%). In semisolid-media, CD34posCD36neg cells generated BFU-E and CFU-GM (in a 1 : 1 ratio), CD34negCD36neg cells mostly BFU-E (87%) and CD34posCD36pos and CD34negCD36low cells were not tested due to low numbers. Under HEMA conditions, CD34posCD36neg, CD34posCD36pos, CD34negCD36low and CD34negCD36neg cells generated EBs with fold-increases of ≈9,000, 100, 60 and 1, respectively, and maturation times (day with >10% CD36highCD235ahigh cells) of 10–7 days. Pyrenocytes were generated only by CD34neg/CD36neg cells by day 15. These results confirm that the majority of HPC in AB express CD34 but identify additional CD34neg populations with erythroid differentiation potential which, based on differences in fold-increase and maturation times, may represent a hierarchy of HPC present in AB

Reprogramming of human keratinocytes into functional cardiomyocytes

Purpose. Induced pluripotent stem cells (iPS) can be generated by patients intro- ducing transcription factors that are highly expressed in embryonic stem (ES) cells into somatic cells. However, the various iPS cell lines are characterized by different properties such as differentiation efficiency and potential safety hazards. Among several readily available primary human somatic cell types, keratinocytes can be isolated easily from human skin or hair follicle, and therefore represent an attractive cell source for reprogramming. The aims of the present study were: 1. To assess the cardiomyogenic potential of human keratynocytes-derived iPS. 2. To increase the differentiation efficiency in order to obtain a homogeneous population of beating cardiomyocytes, also overcoming the limitation of embryonic body formation.Methods. Established iPS cell line obtained from human keratinocytes was cultured in monolayer and exposed sequentially to Ascorbic Acid, 5-Azacytidine, BMP4, ActivinA, VEGF up to 20 days. Differentiation was evaluated monitoring the expression of Nkx2.5, Gata4, sarcomeric α-actinin, α cardiac myosin heavy chain, cardiac T-troponin and Connexin43 and β-adrenoceptors as cardiac markers, by Western Blot, immunofluorescent and cytometric analyses. An ImageStream analysis for a simulta- neous quantitative and morphological evaluation was also performed.Results. During the differentiation induction, iPS became positive to all the analyzed cardiac markers. In particular, we observed a rapid and significant increase of Nkx2.5 and Gata4 expression (14.7±0.7% vs 43.2±2.1% Nkx2.5+ and 21.7±1.2 vs 65.9±3.6% Gata4+ in iPS and 15 days after the induction respectively, p&lt;.005, analy- sis by ImageStream), with a significant nuclear translocation (nuclear+ cells:7.2±0.8% vs 18.8±2.1% of the Nkx2.5+ cells in iPS and 15 days after the induction respectively, p&lt;.005, analysis by ImageStream). The differentiation process was accompanied by a modulation of β1- and β2-adrenoceptors expression. Foci of spontaneous contraction were observed after only 5 days from the induction and after 15 days the beating cells represented about the 60-90% of the entire population. Moreover, differentiated cardio- myocytes responded to adrenergic stimulation by increasing the contraction rate. Conclusion. iPS obtained from hKeratinocytes efficiently differentiate into cardi- omyocytes giving rise to a homogenous population with cardiac-specific molecular and functional properties

Non-Aβ-dependent factors associated with global cognitive and physical function in alzheimer's disease: a pilot multivariate analysis

Recent literature highlights the importance of identifying factors associated with mild cognitive impairment (MCI) and Alzheimer's Disease (AD). Actual validated biomarkers include neuroimaging and cerebrospinal fluid assessments; however, we investigated non-Aβ-dependent factors associated with dementia in 12 MCI and 30 AD patients. Patients were assessed for global cognitive function (Mini-Mental state examination-MMSE), physical function (Physical Performance Test-PPT), exercise capacity (6-min walking test-6MWT), maximal oxygen uptake (VO₂max), brain volume, vascular function (flow-mediated dilation-FMD), inflammatory status (tumor necrosis factor-α ,TNF- α, interleukin-6, -10 and -15) and neurotrophin receptors (p75NTR and Tropomyosin receptor kinase A -TrkA). Baseline multifactorial information was submitted to two separate backward stepwise regression analyses to identify the variables associated with cognitive and physical decline in demented patients. A multivariate regression was then applied to verify the stepwise regression. The results indicated that the combination of 6MWT and VO₂max was associated with both global cognitive and physical function (MMSE = 11.384 + (0.00599 × 6MWT) - (0.235 × VO₂max)); (PPT = 1.848 + (0.0264 × 6MWT) + (19.693 × VO₂max)). These results may offer important information that might help to identify specific targets for therapeutic strategies (NIH Clinical trial identification number NCT03034746)

Angiogenetic effects of physical exercise in menopausal women

Introduction: With menopause women face many changes that may lead to the loss of health related fitness, especially if sedentary. In particular, the estrogens deficiency affects the endothelial function thus increasing the incidence of the cardiovascular diseases. The cardio-protective effects of physical exercise is at least partially due to its ability to improve the health of arterial walls by influencing the endothelial function. Nonetheless, a direct angiogenetic of the physical exercise cannot be ruled out. VEGF is an important modulator of vascular growth but there are contrasting results about its response to physical exercise. Aim of our study was to compare the effects of two aerobic training on the VEGF levels and on the angiogenesis in postmenopausal women. Material and Methods. 34 Postmenopausal women underwent a 13 weeks training. In order to analyse the angiogentic effects, plasmatic VEGF levels were analysed before (T0) and after the training (T1). Moreover, the ability of the T0 and T1 serum to chemoattract endothelial cells and to induce them to form tubes was analyzed. Results: All post-menopausal women increase VEGF (P=0,014) after training. In vitro tests evidenced that when cultured in presence of T1 serum, HUVEC cells improved their ability to form tube (P&lt;0,001) as well as their calibre (P&lt;0,001). Moreover, migration assays evidenced that after training the serum chemoattractive capacity increased significantly (P&lt;0,001) capacity. Conclusion: Our data evidence that aerobic training influence the arterial wall physiology also inducing a angiogenetic affect

Effect of short-term aerobic exercise on cardiovascular remodelling in post-menopause women

It is well known that menopause is associated with an increase of cardiovascular (CV) risk factors, including changes on metabolic profile, body composition, haemdynamic loads and cardiovascular remodelling. The latter starts with an increase of arterial elastance and early concentric left ventricular remodeling, manifested by an increment of the relative wall thickness. We investigated morphological and functional effects of short-term aerobic exercise at moderate intensity without diet restriction on cardiovascular apparatus in post-menopause women. Seventy-six post-menopausal healthy sedentary postwomen (56± 4 yrs) underwent clinical history, physician and anthropometric exam, 12-lead electrocardiography. Echocardiography was used to assess LV geometry and systolic and diastolic functions. Relative diastolic wall thickness (RWT), midwall fractional shortening (MFS) and arterial elastance (AE) were calculated to evaluate the LV concentric remodeling, the intrinsic systolic function and the vascular load, respectively. Data were collected before and after 14 weeks of moderate aerobic exercise training (four time per week). After the intervention program, systolic and diastolic arterial pressure, heart rate and hip circumference were significantly decreased (P = 0,01; P = 0,00; P = 0,00; P = 0,01, respectively). Left ventricular mass/height 2.7, ejection fraction and MFS were higher (p&lt; 0,00; P= 0,00; P =0,00), while relative wall thickness (RWT) and AE were lower (P&lt;0,03;P=0,00). Mitral E wave and E/A were higher (P = 0,001; P&lt;0,0001). Left ventricular mass/height 2.7 was correlated to BMI (P = 0,04), WC (P = 0,034) and waist/hip ratio (P = 0,007). In post-menopause women aerobic exercise improves CV function (concentric remodelling, diastolic and systolic function) acting both on haemodynamic factors and body composition. Our data underline the role of non pharmacological interventions in the CV disease prevention

Combining Core Training and Sensory Refinement: effects on physical performance

The concept of “the Core” describes the complex of anatomical components of the trunk, pelvis and shoulder girdle that are responsible for maintaining the stability of the spine and pelvis and are critical for the transfer of energy from larger torso to the smaller extremities, during many sport and daily-living activities (1). This concept rooted in sport science and rehabilitation and recently Core Training (CT) became very popular as a method to prevent injuries and improve sport performance and physical fitness. It consists in the progressive training of the musculature of the Core with special emphasis in posture and lumbar spine stability. This aspect requires a fine coordination and body awareness that often are poor developed or regressed after an injury. Then, it is important to include exercises of Sensorial Refinement (SR) that may stimulate the refinement of perceptually neglected areas (2). The aim of the study was to evaluate the effect of combined CT and SR on physical performance and to compare these effects with traditional core training. Furthermore, the effect on retention after 4 weeks of detraining was evaluated. Two groups of participants were recruited (age >30 < 50) and assigned to experimental (CT and SR: EXP, n = 9) or control (CT: CON, n = 9) group. Both groups trained ten weeks, with a frequency of two sessions per week. Training consisted in 10’ of warm up, 40’ of workout and 10’ of cool down. Workout of EXP group consisted in 20’ of SR and 20’ of CT whereas CON group performs 40’ of CT. Participants where tested by: Star Excursion Balance Test (SEBT) for the dynamic balance of lower body, Upper Quarter Y Balance Test (YBT-UQ) to assess upper extremities function in a closed-chain position and McGill test to evaluate muscular endurance of the core. Both groups improved core endurance after training and worsen it at follow up; moreover, both groups ameliorate upper an lower body control (SEBT and YBT-UQ) after training but only EXP group improved or maintained it at follow up. Since the information about the movements of the body are elaborated in the somatomotor cortex for fine coordination, the combination of CT and SR should better promote the consolidation of motor memory and long-term body control

Study of cardiomyogenic potential of human Amniotic Fluid Stem Cells

It has been shown that Amniotic fluid stem cells (AFSCs) have characteristics intermediate between pluripotent embryonic and lineage-restricted adult stem cells, and are non-tumorigenic and low immunogenic. Moreover, they are obtained without destroying human embryos, so that preventing most of the ethical and social controversy. Human AFSCs express some genes specific of both embryonic (OCT3/4, NANOG, c-MYC) and primordial germ stem cells (Fragilis, Stella, c-KIT). We have demonstrated that hAFSCs form in vitro embryoid bodies (EBs) and express markers of three germ layers. Studies reported the ability of hAFSCs to differentiate in vitro into adipocytes and osteocytes, but only few data are available on their cardiomyogenic potential. Aim of this study is to analyze hAFSCs differentiation through the cardiac pathway. Embryonic Bodies (EBs) were obtained from hAFSCs cultured in presence of ascorbic acid and 5-aza-2’-deoxycytidine. Cardiomyogenic potential of hAFSCs and EBs was explored by WB and immunoflorescent analyses of specific markers. Simultaneous quantitative detection and cellular localization analysis of cardiomyogenic markers were conducted with an ImageStream multispectral imaging flow cytometer (Amnis-Seattle, WA) equipped with IDEAS statistical software. We evidenced that both AFSCs and EBs at early stage express Nkx2.5, a transcription factor expressed by cardiomyocytes precursor cells. Moreover, ImageStream imaging cytometer analysis evidenced that EBs formation was accompanied by an up-regulation of Nkx2.5 expression (36.54±1.83% and 64.68±3.23% positive cells in hAFSC and EBs respectively, p&lt;.005) and by a significant nuclear translocation (12.98±0.64% and 37.98±1.9% nuclear positive cells in hAFSC and EBs respectively, p&lt;.005). Microscopical analysis evidenced inside the EBs cells positive for the presence of cardiac α-Myosin heavy chain protein structurally organized in oriented filaments. Moreover, we detected cells expressing Connexin43. These results evidenced that EBs obtained from hAFSCs cultured in permissive conditions terminally differentiate into cardiomyocytes and suggest them as possible model to study the cardiac differentiation