View clinical trials related to Endothelial Dysfunction.
Filter by:High blood pressure (BP) is the major modifiable risk factor for cardiovascular diseases (CVD) and related health conditions, particularly among postmenopausal (PM) women. In adults age ≥50 years this risk is primarily driven by above-normal systolic BP (SBP ≥120 mmHg), as diastolic BP plateaus, then decreases in older adulthood. Although SBP is lower in premenopausal women vs. age-matched men, SBP reaches, then surpasses men after age 60. As such, >75% of PM women in the U.S. have above-normal SBP, which, in turn, is responsible for a 2-fold increase in risk of hypertension and corresponding increases in risk of CVD, chronic kidney disease and many other disorders. A key process linking high SBP to CVD and related conditions is vascular endothelial dysfunction, mediated by excessive reactive oxygen species (ROS)-induced oxidative stress and reductions in nitric oxide (NO) bioavailability. As the number of PM women is rapidly growing, further increases in SBP-related CV disorders are projected without effective intervention. - Aerobic exercise (AE) is a first-line, standard-of-care therapy for lowering BP. In PM women with baseline SBP ≥120 mmHg, AE reduces casual (resting) SBP by ~3 mmHg (back to baseline ≤4 weeks post-training), whereas 24-hour SBP is typically unchanged. However, only 25-30% of PM women meet guidelines for 150 min/week of moderate-intensity AE, citing the extensive time requirement, facility access and travel disruptions as major barriers. Another, far less recognized, limitation is that AE training consistently improves endothelial function in midlife/older men, but not in estrogen-deficient PM (PMe-) women, i.e., in >95% of the 60+million PM women in the U.S. Thus, establishing new lifestyle therapies that induce and sustain reductions in SBP and increases in endothelial function in PMe- women with above-normal SBP is an important public health goal. - High-resistance inspiratory muscle strength training (IMST) is a time-efficient (5 minutes per session) lifestyle intervention consisting of 30 inspiratory maneuvers performed against a high resistance. Preliminary data suggest 6-weeks of IMST performed 6 days/week reduces SBP by 9 mmHg in adults with above-normal SBP (i.e., greater than 120 mmHg) at baseline. Importantly, this reduction in SBP is equal to or greater than the reduction in blood pressure typically achieved with time- and effort-intensive healthy lifestyle strategies like conventional aerobic exercise. In addition, IMST improved endothelial function in the PMe- women in a small pilot study. - To translate these promising preliminary results towards clinical practice, this randomized clinical trial is being conducted to directly compare the efficacy of a longer, clinically relevant treatment duration of IMST (3 months) against home-based, moderate-intensity (standard-of-care) AE in PMe-women. The primary outcome will be the change in casual SBP (IMST vs. AE). Changes in 24-hour SBP and endothelial function will serve as secondary outcomes. Effects on NO bioavailability, ROS/oxidative stress, and the role of "circulating factors" will provide insight into mechanisms of action. The sustained effects on SBP and endothelial function also will be assessed. - Accordingly, a randomized, blinded, sham-controlled, parallel group design clinical trial will be conducted to assess the efficacy of 3-months of IMST (75 percent maximal inspiratory pressure) vs. brisk walking (40-60% heart rate reserve; an established healthy lifestyle strategy) for lowering SBP and improving endothelial function in PMe- women age 50 years and older with above-normal SBP. It is hypothesized that IMST will lower SBP and improve endothelial function by decreasing oxidative stress and increasing nitric oxide bioavailability. It is also expect that adherence to the intervention will be excellent (over 80 percent of all training sessions completed at the appropriate intensity). - To test this hypothesis, 90 PMe- women age 50 years and older who have SBP >/= 120 mmHg will be recruited. Participants will undergo baseline testing for casual (resting) SBP, 24-hour ambulatory SBP and endothelial function. Innovative mechanistic probes including pharmaco-dissection with vitamin C, analysis of biopsied endothelial cells, and high-throughput metabolomics, will be performed to assess oxidative stress and nitric oxide bioavailability at baseline. - After baseline testing, subjects will be randomized to perform either 3-months of high-resistance IMST or brisk walking. Subjects will train 6 days/week. Following 3 months of training, subjects will redo all the tests that were done during baseline testing to assess training-induced changes in SBP, physiological functions, and underlying mechanisms. Subjects will then cease training for 6 weeks before returning to the lab for follow-up testing to determine the persistent effects of IMST.
Explore the effects of anti-VEGF targeted drugs on blood pressure and endothelial function in cancer patients.
Above-normal systolic blood pressure (SBP), defined as SBP >/= 120 mmHg, is the major modifiable risk factor for cardiovascular disease, stroke, cognitive decline/dementia, and other chronic health problems. Despite the availability of treatments to lower SBP, over 75 percent of adults with above-normal SBP fail to control BP, which has led to a nearly 50 percent increase in the number of deaths attributable to BP over the past decade. Therefore, above-normal SBP is a major public health burden. - Greater than 65 percent of adults 50 years of age and older have above-normal SBP. The number of adults age 50 years and older is rapidly increasing, predicting a continued increase in above-normal SBP driven morbidity and mortality in the absence of effective treatment strategies. This makes developing novel SBP-lowering therapies an urgent biomedical research priority. - Increasing SBP is closely linked to vascular dysfunction, observable as impaired endothelial function, increased large-elastic artery stiffness, and impaired cerebrovascular function. Declines in these functions play a large role in the increased risk of chronic disease associated with above-normal SBP. The primary mechanism responsible for SBP-induced vascular dysfunction is thought to be oxidative stress-associated inhibition of nitric oxide bioavailability. Therefore, to have the largest biomedical impact, new SBP-lowering therapies should also improve vascular function by decreasing oxidative stress. - Healthy lifestyle practices, such as conventional aerobic exercise, maintaining a healthy diet, or reducing sodium intake, are all first-line strategies to lower SBP. Importantly, these lifestyle practices also improve vascular function, in large part by reducing oxidative stress. However, adherence to healthy lifestyle practices is poor, with adherence to guidelines generally between 20 to 40 percent in adult Americans. The greatest reported barrier to meeting healthy lifestyle guidelines is lack of time. Therefore, time-efficient interventions have great promise for promoting adherence, reducing SBP, and improving other physiological functions. - High-resistance inspiratory muscle strength training (IMST) is a time-efficient (5 minutes per session) lifestyle intervention consisting of 30 inspiratory maneuvers performed against a high resistance. Preliminary data suggest 6-weeks of IMST performed 6 days/week reduces SBP by 9 mmHg in adults with above-normal SBP (i.e., greater than 120 mmHg) at baseline. Importantly, this reduction in SBP is equal to or greater than the reduction in blood pressure typically achieved with time- and effort-intensive healthy lifestyle strategies like conventional aerobic exercise. However, these results need to be confirmed in an appropriately powered clinical trial with a longer, guideline-based treatment duration. Furthermore, the influence of IMST on functions impaired by above-normal SBP (endothelial, cerebrovascular, cognitive) needs to be determined, as do the mechanisms through which IMST exerts beneficial effects. - Accordingly, we will conduct a randomized, blinded, sham-controlled, parallel group design clinical trial to assess the efficacy of 3-months of IMST (75 percent maximal inspiratory pressure) vs. brisk walking (40-60% heart rate reserve; an established healthy lifestyle strategy) for lowering SBP and improving endothelial, cerebrovascular, and cognitive function in adults age 50 years and older with above-normal SBP. I hypothesize IMST will lower SBP and improve endothelial function by decreasing oxidative stress and increasing nitric oxide bioavailability. I also hypothesize IMST will improve cerebrovascular and cognitive function, and that these improvements will be related to reductions in SBP and improvements in endothelial function. I also expect adherence to the intervention to be excellent (over 80 percent of all training sessions completed at the appropriate intensity). - To test my hypothesis, I will recruit 102 adults age 50 years and older who have SBP >/= 120 mmHg. Subjects will undergo baseline testing for casual (resting) SBP, 24-hour ambulatory SBP, endothelial function, arterial stiffness, cognitive function, and cerebrovascular function. Innovative mechanistic probes including pharmaco-dissection with vitamin C, analysis of biopsied endothelial cells, and high-throughput metabolomics, will be performed to assess oxidative stress and nitric oxide bioavailability at baseline. - After baseline testing, subjects will be randomized to perform either 3-months of high-resistance IMST or brisk walking. Subjects will train 6 days/week with one training session supervised in the laboratory and the other 5 performed unsupervised at home. Following 3 months of training, subjects will redo all the tests that were done during baseline testing to assess training-induced changes in SBP, physiological functions, and underlying mechanisms.
The ongoing pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) has infected more than one hundred twenty million peoples worldwide one year after its onset with a case-fatality rate of almost 2%. The disease due to the coronavirus 2019 (i.e., COVID-19) is associated with a wide range of clinical symptoms. As the primary site of viral invasion is the upper respiratory airways, lung infection is the most common complication. Most infected patients are asymptomatic or experience mild or moderate form of the disease (80 %). A lower proportion (15%) develop severe pneumonia with variable level of hypoxia that may required hospitalization for oxygen therapy. In the most severe cases (5%), patients evolve towards critical illness with organ failure such as the acute respiratory distress syndrome (ARDS). At this stage, invasive mechanical ventilation is required in almost 70 % and the hospital mortality rises to 37 %. Immune cells are key players during SARS CoV-2 infection and several alterations have been reported including lymphocytes (T, B and NK) and monocytes depletion, and cells exhaustion. Such alterations were much more pronounced in patients with the most severe form of the disease. Beside, a dysregulated proinflammatory response has also been pointed out as a potential mechanism of lung damage. Finally, COVID-19 is associated with an unexpectedly high incidence of thrombosis which probably results from the viral invasion of endothelial cells. The investigators aim to explore prospectively the alterations of innate and adaptive immune cells during both the acute and the recovery phase of SARS CoV-2 pneumonia. Flow and Spectral cytometry will be used to perform deep subset profiling focusing on T, B, NK, NKT, gamma-gelta T, monocytes and dendritic cells. Each specific cell type will be further characterized using markers of activation/inhibition, maturation/differenciation and senescence as well as chemokines receptors. T-cell memory specificity will be explore using specific SARS CoV-2 pentamer. Platelet activation and circulating microparticles will be explore using flow cytometry. Serum SARS CoV-2 antibodies (IgA, IgM, IgG), serum cytokines, and serum biomarkers of alveolar epithelial and endothelial cells will be analyze using ELISA and correlate with the severity of the disease.
COVID-19 Infection has been found to cause endothelial dysfunction and most of the adverse events stem to this mechanism. So we seek to target endothelial dysfunction in critically Ill patients with covid by giving them an endothelial protocol ( L-arginine, Folic Acid, Statin, Nicorandil, Vitamin B complex) and monitor clinical outcome in those patients.
This study will examine the impact of cardiac rehabilitation on blood vessel health using a newly developed microfluidic-based tactile sensor to assess blood vessel health. The participants will have their blood vessel health measured using a sensor that is placed on top of the skin over the artery before and after exercise (1, 3, 5, 10, 30 and 60 mins). The investigators will study these responses at the first session of cardiac rehabilitation and following 1 and 4 weeks of cardiac rehabilitation (sessions 3 and 6). The investigators will also collect some information from the medical record regarding: age, gender, body mass index, resting cardiovascular measures (heart rate, blood pressure etc), medications, reasons which qualified the participant into cardiac rehabilitation, blood tests related to heart or cardiovascular function, metabolic panel, lipid panel, echocardiogram results, recorded electrocardiogram, known vascular diseases, presence of implantable devices, Seattle Heart Failure Model data and cardiovascular measures and exercise workloads during cardiac rehabilitation.
Hypertension is a progressive cardiovascular syndrome caused by multiple causes, which can lead to changes in the function and structure of the heart and blood vessels. It is the leading risk factor of cardiovascular disease. Berberine (BBR) hydrochloride is an isoquinoline alkaloid (chemical formula: C20H18NO4) extracted from traditional Chinese herb Coptis chinensis. It has been widely used to treat diarrhea and enteritis for hundreds of years in China. BBR has extremely high clinical application value. It is an over-the-counter drug with low price, good safety and few adverse reactions in China. We found that Berberine (BBR) hydrochloride tablets have a hypotensive effect in clinical practice. However, there are few clinical studies on the treatment of hypertensive patients with BBR tablets. In addition, the clinical dosage of BBR tablets is not uniform, and its molecular mechanism is still unclear. In order to further evaluate the clinical efficacy of BBR in reducing blood pressure and improving vascular endothelial injury, we carried out this clinical trial of drug intervention for hypertensive population. After signed the informed consent, the subjects are assigned to the lifestyle intervention group (CON) and berberine hydrochloride group (BBR). The berberine hydrochloride group (BBR) take berberine hydrochloride tablets (0.4g, 3 times/day, 3 months) . We will follow up blood pressure and vascular endothelial function in 1 month and 3 months after taking the medicine.
Specific Aim 1: To test the hypothesis that prolonged (3-month) treatment with galantamine inhibits NADPH IsoLG-protein adducts formation and improves markers of endothelial cell (EC) dysfunction in AAs. Aim 1a: The investigators will determine if galantamine inhibits NADPH IsoLG-protein adducts formation, superoxide production, and immune cell activation compared to placebo. For this purpose, the investigators will study peripheral blood mononuclear cell (PBMC), a critical source of systemic oxidative stress, collected from study participants. Aim 1b: The investigators will determine if galantamine reduces intracellular Iso-LGs, ICAM-1, and 3-nitrotyrosine, a marker of vascular oxidative stress, in ECs harvested from study participants. Specific Aim 2: To determine if prolonged (3-month) treatment with galantamine improves endothelial dysfunction as measured by vascular reactivity in AAs. The investigators will measure vascular reactivity in response to ischemia in two vascular beds: (a) in conduit arteries (brachial artery) using brachial artery diameter flow-mediated dilation (FMD), and (b) in the microvasculature (MBV) using contrast-enhanced ultrasonography in skeletal muscle. This proposal will study a novel mechanism that could alter the oxidative and immunogenic responses that contributes to endothelial dysfunction in AAs and will offer a potential pathway for the development of more effective therapies aimed at decreasing the progression of endothelial dysfunction to cardiovascular disease in this population.
The researchers intend to recruit individuals who are referred for a routine screening in the primary prevention outpatient clinic of Attikon University hospital, Athens According to institutional protocols, a detailed medical history for atherosclerotic risk factors and current medication is recorded and a baseline clinical examination is performed. Moreover fasting blood samples are drawn to diagnose the presence of diabetes mellitus and hyperlipidemia. Glycocalyx examination is performed at the same visit. The subjects are revaluated at one month and then followed up according to the attending physician's instructions. Pulse wave velocity and the rest pulse wave analysis parameters were also calculated to determine the additive predictive value for cardiovascular events beyond SCORE2. All subjects are followed up for adverse events (death, stroke, myocardial infarction, hospitalization for heart failure) for 6 years after enrollment via telephonic contact and planned appointment at the outpatient clinic.
Cardiac surgery has been described as altering endothelium structure and function, notably because of the use of cardiac-pulmonary bypass (CPB). Among the endothelial structure, glycocalyx, the thin layer recovering the endothelial surface, may be altered by the inflammatory process and probably the modification of flow during CPB. Endothelial and glycocalyx integrity are essential for vascular function and glycocalyx destruction is associated with organ failure and mortality. On the other hand, a chronic alteration of glycocalyx is observed in many diseases such as diabetes, hypertension or chronic kidney failure, all pathologies frequently observed in patients benefiting grom cardiac surgery. Thus the preoperative alteration of glycocalyx may be associated with postoperative organ failure.