Monocyte Phenotypes and Physical Activity in Patients with Carotid Atherosclerosis.

Atherosclerosis is associated with low-grade inflammation involving circulating monocytes. It has been shown that the levels of intermediate pro-inflammatory monocytes are associated with cardiovascular mortality and risk of ischemic stroke. It also has been shown that physical activity (PA) decreases inflammation markers, incidence of strokes, and mortality. In this cross-sectional study, we tested the effect of PA on circulating monocytes phenotype rate. A total of 29 patients with a carotid stenosis > 50% were recruited. Levels of physical activity (MET.min/week) were measured by the GPAQ questionnaire, arterial samples of blood were collected to analyze monocyte phenotype (classical, intermediate and non-classical) assessed by flow cytometry, and venous blood samples were used to dose antioxidant activity and oxidative damage. Antioxidant capacity was reduced and oxidative damage increased in patients. There was a significant decrease in the percentage of classical and intermediate monocytes in moderately active patients as compared with non-active and highly active patients. Inversely, the rate of non-classical monocytes increased in moderately active patients. Intense PA appears to blunt the beneficial effects of moderate PA. Our study also suggests that PA could be beneficial in such patients by reducing the rate of intermediate monocytes known to predict the risk of ischemic stroke and by increasing the non-classical monocytes involved in lesions' healing. Nevertheless, a longitudinal study would be necessary to confirm this hypothesis.

Effectiveness of an individualized home-based physical activity program in surgery-free non-endarterectomized asymptomatic stroke patients: a study protocol for the PACAPh interventional randomized trial.

BACKGROUND: Carotid atherosclerotic plaques remain silent until their rupture, which may lead to detrimental ischemic events such as strokes. This is due, in part, to intraplaque hemorrhages (IPH) and the resulting inflammatory processes, which may promote carotid plaque vulnerability. Currently, the benefits of carotid endarterectomy remain unclear for asymptomatic patients. Interestingly, the completion of physical activity (PA) may have beneficial effects; however, the paucity of current data warrants robust longitudinal interventions. We therefore aim to study the effects of a 6-month longitudinal personalized home-based PA program on IPH, biological, and inflammatory markers in asymptomatic stroke patients. METHODS: Eighty patients (≥ 18 years old) will be recruited for the Physical Activity and Carotid Atherosclerotic Plaque Hemorrhage (PACAPh) clinical trial from the Hospices Civils de Lyon. Patients will be eligible if they present with carotid stenosis ≥ 50% and are asymptomatic from any ischemic events for at least 6 months. Recruited patients will be randomized into either a PA or a control group, and assessed at baseline and after 6 months. At both time points, all patients will be assessed using magnetic resonance imaging to assess IPH, blood sampling to measure inflammatory markers and monocytic phenotyping, PA and sedentary behavior questionnaires, 6-min walking test, and maximal isometric quadricep contraction test. The randomized PA intervention will consist of reaching a daily walking step goal individually tailored to each patient. Steps will be collected using a wirelessly connected wristband. The number of steps completed by individuals in the PA group will be re-evaluated bimonthly to encourage walking habits. DISCUSSION: The PACAPh study is the first of its kind representing a feasible, easily accessible therapeutic strategy for asymptomatic stroke patients. We hypothesize that the personalized home-based PA program will reduce IPH and modulate inflammatory and biological parameters in patients presenting with carotid plaques. If the results of the PACAPh study prove to be beneficial on such health parameters, the implementation of such kind of intervention in the daily treatment of these patients would be an advantageous and cost-effective practice to adopt globally. TRIAL REGISTRATION: This study has been approved by the National Ethics Committee (IDRCB:2019-A01543-54/SI:19.06.21.40640). ClinicalTrials.gov NCT04053166.

Beneficial Effects of High Intensity Interval Training and/or Linseed Oil Supplementation to Limit Obesity-Induced Oxidative Stress in High Fat Diet-Fed Rats.

High-intensity interval training (HIIT) and linseed oil (LO) supplementation are effective strategies to reduce obesity-induced oxidative stress. Our aim was to determine whether the HIIT + LO combination prevents obesity-induced oxidative stress in high fat diet (HFD)-fed rats. HFD-fed 8-week-old, male, Wistar rats were subdivided in four groups: HFD, LO (2% of sunflower oil replaced with 2% of LO in the HFD), HIIT (4 days/week for 12 weeks), and HIIT + LO. Wistar rats fed a low-fat diet (LFD) were used as controls. Epididymal and subcutaneous adipose tissue, gastrocnemius muscle, liver, and plasma samples were collected to measure oxidative stress markers (AOPP, oxLDL), antioxidant (SOD, CAT, and GPx activities) and pro-oxidant (NOx and XO) enzyme activities. Compared with the LFD, the HFD altered the pro/antioxidant status in different tissues (increase of AOPP, oxLDL, SOD and catalase activities in plasma, and SOD activity increase in liver and decrease in adipose tissues) but not in gastrocnemius. LO upregulated CAT activity and decreased NOx in liver. HIIT alleviated HFD negative effects in liver by reducing SOD and NOx activities. Moreover, the HIIT + LO combination potentiated SOD activity upregulation in subcutaneous tissue. HIIT and LO supplementation have independent beneficial effects on the pro/antioxidant balance. Their association promotes SOD activity in subcutaneous adipose tissue.

Combining proactive transcranial stimulation and cardiac biofeedback to substantially manage harmful stress effects.

BACKGROUND: Previous studies have identified the dorsolateral prefrontal cortex (dlPFC) as a core region in cognitive emotional regulation. Transcranial direct current stimulations of the dlPFC (tDCS) and heart-rate variability biofeedback (BFB) are known to regulate emotional processes. However, the effect of these interventions applied either alone or concomitantly during an anticipatory stress remains unexplored. OBJECTIVE: The study investigated the effect of anodal tDCS and BFB, alone or combined, on psychophysiological stress responses and cognitive functioning. METHODS: Following a stress anticipation induction, 80 participants were randomized into four groups and subjected to a 15-min intervention: neutral video viewing (ctrl), left dlPFC anodal tDCS (tdcs), heart-rate variability biofeedback (bfb), or a combined treatment (bfb + tdcs). Participants were then immediately confronted with the stressor, which was followed by an assessment of executive functions. Psychophysiological stress responses were assessed throughout the experiment (heart rate, heart-rate variability, salivary cortisol). RESULTS: The tdcs did not modulate stress responses. Compared with both ctrl and tdcs interventions, bfb reduced physiological stress and improved executive functions after the stressor. The main finding revealed that bfb + tdcs was the most effective intervention, yielding greater reduction in psychological and physiological stress responses than bfb. CONCLUSIONS: Combining preventive tDCS with BFB is a relevant interventional approach to reduce psychophysiological stress responses, hence offering a new and non-invasive treatment of stress-related disorders. Biofeedback may be particularly useful for preparing for an important stressful event when performance is decisive.

Carotid intraplaque haemorrhage: pathogenesis, histological classification, imaging methods and clinical value.

Vulnerable carotid atherosclerotic plaques are characterised by several risk factors, such as inflammation, neovascularization and intraplaque haemorrhage (IPH). Vulnerable plaques can lead to ischemic events such as stroke. Many studies reported a relationship between IPH, plaque rupture, and ischemic stroke. Histology is the gold standard to evaluate IPH, but it required carotid endarterectomy (CEA) surgery to collect the tissue sample. In this context, several imaging methods can be used as a non-invasive way to evaluate plaque vulnerability and detect IPH. Most imaging studies showed that IPH is associated with plaque vulnerability and stroke, with magnetic resonance imaging (MRI) being the most sensitive and specific to detect IPH as a predictor of ischemic events. These conclusions are however still debated because of the limited number of patients included in these studies; further studies are required to better assess risks associated with different IPH stages. Moreover, IPH is implicated in plaque vulnerability with other risk factors which need to be considered to predict ischemic risk. In addition, MRI sequences standardization is required to compare results from different studies and agree on biomarkers that need to be considered to predict plaque rupture. In these circumstances, IPH detection by MRI could be an efficient clinical method to predict stroke. The goal of this review article is to first describe the pathophysiological process responsible for IPH, its histological detection in carotid plaques and its correlation with plaque rupture. The second part will discuss the benefits and limitations of imaging the carotid plaque, and finally the clinical interest of imaging IPH to predict plaque rupture, focusing on MRI-IPH.

Impact of aerobic exercise, sex, and metabolic syndrome on markers of oxidative stress: results from the Brain in Motion study.

Oxidative stress may be involved in disease pathology and dependent on both modifiable and nonmodifiable factors. This study aimed to assess exercise-induced changes in markers of oxidative stress among older, sedentary adults and to determine the effects of metabolic syndrome (MetS) status, aerobic capacity, age, sex, and weight on these biomarkers. Two hundred and six participants (means ± SE; 66.8 ± 6.4 yr, 104 women) of the Brain in Motion study underwent a 6-mo aerobic exercise intervention. At three time points, venous blood samples were collected and analyzed for markers of oxidative stress [advanced oxidation protein products (AOPP), malondialdehyde (MDA), 3-nitrotyrosine (3-NT) and antioxidant status: catalase, uric acid (UA), superoxide dismutase (SOD), and ferric-reducing ability of plasma (FRAP)]. AOPP levels significantly decreased after 6 mo of aerobic exercise (P = 0.003). This decrease was not modified by MetS status (P = 0.183). Subjects with MetS possessed significantly higher levels of AOPP (P < 0.001), MDA (P = 0.004), and FRAP (P = 0.049) across the intervention (months 0-6). Men possessed significantly higher levels of FRAP (P < 0.001), catalase (P = 0.023), and UA (P = 0.037) across the intervention (months 0-6). Sex-MetS status interaction analyses revealed that the effect of MetS is highly sex dependent. These findings are multifaceted because the effect of MetS status seems distinctly different between sexes, pointing to the importance of acknowledging modifiable and nonmodifiable factor differences in individuals who possess conditions where oxidative stress may be part of the etiology.NEW & NOTEWORTHY Oxidative stress is implicated in a myriad of conditions, namely cardiovascular disease risk factors. This article details the effect of aerobic exercise, sex, and metabolic syndrome on markers of oxidative stress. We conclude that 6 mo of aerobic exercise significantly decreased oxidative stress, and further, that there is an effect of metabolic syndrome status on oxidative stress and antioxidant status levels, which are highly dependent on the sex of the individual.

Association between physical activity and sedentary behaviour on carotid atherosclerotic plaques: an epidemiological and histological study in 90 asymptomatic patients.

OBJECTIVE: Carotid atherosclerotic plaques are a source of emboli for stroke. 'Unstable' carotid atherosclerotic plaques may have intraplaque haemorrhages, neovessels, prevalent macrophages, excessive calcium deposits, a large lipid core and a thin fibrous cap. Regular physical activity (PA) may lower the risk of plaques becoming unstable. We evaluated the association of both PA and sedentary behaviour (SB) with carotid plaque histopathology. METHODS: 90 asymptomatic patients who were undergoing carotid endarterectomy for carotid artery narrowing identified on ultrasound reported their PA and SB by questionnaires. We calculated PA intensity in MET (metabolic equivalent of task)-min/week. For analysis, the population was divided into tertiles according to PA (T1PA: the less PA patients; T2PA: the intermediate PA patients; T3PA: the most physically active patients) (T1PA900 and <900 MET-min/week, respectively). All the other features that associate with plaque instability (eg, neovessels, macrophages, etc) did not differ by level of PA or SB. CONCLUSION: In this cross-sectional study of asymptomatic patients who underwent endarterectomy (i) higher reported PA, (ii) intensity of PA and (iii) lower reported SB were associated with lower prevalence of intraplaque haemorrhage. This could be a mechanism whereby PA protects against cerebrovascular disease (stroke) and death.

Oxidative Stress and Inflammation, Key Targets of Atherosclerotic Plaque Progression and Vulnerability: Potential Impact of Physical Activity.

Atherosclerosis, a complex cardiovascular disease, is a leading cause of mortality and morbidity worldwide. Oxidative stress and inflammation are both involved in the development of atherosclerotic plaque as they increase the biological processes associated with this pathology, such as endothelial dysfunction and macrophage recruitment and adhesion. Atherosclerotic plaque rupture leading to major ischemic events is the result of vulnerable plaque progression, which is a result of the detrimental effect of oxidative stress and inflammation on risk factors for atherosclerotic plaque rupture, such as intraplaque hemorrhage, neovascularization, and fibrous cap thickness. Thus, both are key targets for primary and secondary interventions. It is well recognized that chronic physical activity attenuates oxidative stress in healthy subjects via the improvement of antioxidant enzyme capacities and inflammation via the enhancement of anti-inflammatory molecules. Moreover, it was recently shown that chronic physical activity could decrease oxidative stress and inflammation in atherosclerotic patients. The aim of this review is to summarize the role of oxidative stress and inflammation in atherosclerosis and the results of therapeutic interventions targeting them in both preclinical and clinical studies. The effects of chronic physical activity on these two key processes are then reviewed in vulnerable atherosclerotic plaques in both coronary and carotid arteries.

Higher Daily Physical Activity Level Is Associated with Lower RBC Aggregation in Carotid Artery Disease Patients at High Risk of Stroke.

Aim: Carotid artery disease (CAD) is an atherosclerotic inflammatory disease that affects the arterial wall, specifically at points of bifurcation where blood flow is disturbed. Abnormal blood rheology could participate in the pathophysiology of ischemic cardiovascular disease. Physical activity (PA) is known to improve blood rheology in several chronic disorders. This study aims to (i) compare the hemorheological profile of CAD patients and controls and (ii) investigate the associations between daily PA and hemorheological parameters in CAD patients. Methods: Blood viscosity, red blood cell (RBC) aggregation and RBC deformability were assessed in 80 patients (15 symptomatic and 65 asymptomatic) and 14 age-matched controls. Patients' PA levels were evaluated using questionnaires. Results: Symptomatic patients showed increased blood viscosity and RBC aggregation compared to healthy controls. RBC aggregation was significantly lower in the most physically active patients compared to the least physically active ones. Blood viscosity and RBC deformability did not vary according to physical activity level. Conclusions: Our results showed greater hemorheological abnormalities (blood hyper-viscosity and hyper-aggregation of red blood cells) in the most severe CAD patients, which could exacerbate the risk of stroke in patients with stenosis. As the most physically active patients had lower RBC aggregation than those who were less physically active, it is possible that regular PA may limit hemorheological alterations in CAD patients.