scholarly journals Endothelial dysfunction: Mechanisms of development and therapeutic options

2006 ◽  
Vol 59 (7-8) ◽  
pp. 335-341 ◽  
Author(s):  
Srdjan Pesic ◽  
Miroslav Radenkovic ◽  
Leposava Grbovic
Keyword(s):  
Endothelial Dysfunction ◽  
Ace Inhibitors ◽  
Vascular Endothelial Cells ◽  
Beta Blockers ◽  
Phosphodiesterase Inhibitors ◽  
Initial Step ◽  
Endothelial Damage ◽  
Lipid Lowering ◽  
Organic Nitrates ◽  
Vascular Protection

Introduction. Vascular endothelial cells play a key role in cardiovascular regulation by producing a number of potent vasoactive agents, including the vasodilator molecule nitric oxide (NO) and the vasoconstrictor peptide endothelin (ET). Endothelial dysfunction. Endothelial dysfunction is recognized as the initial step in the atherosclerotic process. Impairment of NO synthesis, or increased inactivation of NO by superoxide radicals, may account for the increased peripheral vascular tone, as well as contribute to the clinical consequences of different pathophysiological conditions-which include vascular hypertrophy, increased platelet and monocyte adhesion to the endothelium, atherosclerosis, myocardial infarction and stroke. To date, most interventions attempting to improve endothelial dysfunction have targeted one or more of the numerous risk factors that can cause endothelial damage: hypertension (ACE inhibitors and calcium antagonists), hypercholesterolemia (lipid-lowering agents), cigarette smoking (cessation), sedentary lifestyle (increased physical activity), menopause (estrogen replacement therapy), and diabetes mellitus (control of metabolic abnormalities). Several pharmacologic agents have been suggested to achieve vascular protection through mechanisms that go beyond their primary therapeutic actions (ACE-and HMG-CoA reductase inhibitors). Beneficial changes to the endothelium might result from promotion of vasorelaxation, inhibition of vasoconstriction, reduction in the production of free radicals, or other mechanisms that protect the endothelium from injury. Conclusion. This study deals with the results of many experimental and clinical investigations. The possibility of using different classes of drugs was also established, including ACE inhibitors, Ca-antagonists, AT and endothelin receptor antagonists, direct activator of adenyl cyclase, statins, antioxidants, L-arginine, phosphodiesterase inhibitors, beta-blockers and organic nitrates. .

The SaM (Screening and Monitoring) Approach to Cardiovascular Risk-Reduction in Primary Care—Cyclic Monitoring and Individual Treatment of Patients at Cardiovascular Risk using the Electronic Medical Record

2005 ◽  
Vol 12 (1) ◽  
pp. 56-62
Author(s):  
Israel Rabinowitz ◽  
Ada Tamir
Keyword(s):  
Primary Care ◽  
Risk Factor ◽  
Cardiovascular Risk ◽  
Medical Record ◽  
Electronic Medical Record ◽  
Ace Inhibitors ◽  
Marked Improvement ◽  
Beta Blockers ◽  
Lipid Lowering ◽  
Individual Treatment

Background Cardiovascular disease (CVD) prevention suffers from a major gap between clinical evidence (information) and clinical practice (implementation). Insufficient control risk factor levels and under-utilization of aspirin, statins, angiotensin-converting enzyme (ACE) inhibitors and beta-blockers are well-known examples. Methods The SaM (Screening and Monitoring) approach was devised by a family physician in order to facilitate closure of this gap. It does so by providing solutions to problems in the fields of information and implementation. A simple manipulation of the electronic medical record used in the practice serves to facilitate cyclic monitoring of patients with cardiovascular risk factors. Technological and human resources available in the primary care setting are used. The approach is described in the first part of the article. The second part presents results obtained by employing the approach on one family physician's patient population. Results The final results demonstrate a marked improvement over time in risk factor levels and use of medications in accordance with Indications. The values achieved are superior to those reported in the literature. Blood pressure in hypertensive patients 134/75 mmHg; haemoglobin A1c 7.27%; low-density lipoprotein-cholesterol in patients with CVD or diabetes, 97mg/dl; patients with CVD receiving anti-thrombotic medication, 94%; dyslipidaemic patients with CVD or diabetes receiving lipid-lowering drugs, 90%; post myocardial infarction patients receiving beta-blockers, 76%; hypertensive diabetics or patients with chronic heart failure (CHF) receiving ACE-inhibitors/angiotensin receptor blockers, 86%. Conclusions In this one-practice pilot-study, the SaM approach was employed with marked improvement in risk factor levels and use of appropriate medications. This may translate into reductions in morbidity and mortality in a larger population. Eur J Cardiovasc Prev Rehabil 12:56-62 © 2005 The European Society of Cardiology

scholarly journals Sinapine Thiocyanate Ameliorates Vascular Endothelial Dysfunction in Hypertension by Inhibiting Activation of the NLRP3 Inflammasome

2021 ◽  
Vol 11 ◽  
Author(s):  
Yang Liu ◽  
Hong-lin Yin ◽  
Chao Li ◽  
Feng Jiang ◽  
Shi-jun Zhang ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Nlrp3 Inflammasome ◽  
Vascular Endothelial Cells ◽  
Endothelial Damage ◽  
Endothelial Injury ◽  
Inflammasome Activation ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Nlrp3 Gene ◽  
Spontaneously Hypertensive

The increase of blood pressure is accompanied by the changes in the morphology and function of vascular endothelial cells. Vascular endothelial injury and hypertension actually interact as both cause and effect. A large number of studies have proved that inflammation plays a significant role in the occurrence and development of hypertension, but the potential mechanism between inflammation and hypertensive endothelial injury is still ambiguous. The purpose of this study was to explore the association between the activation of NLRP3 inflammasome and hypertensive endothelial damage, and to demonstrate the protective effect of sinapine thiocyanate (ST) on endothelia in hypertension. The expression of NLRP3 gene was silenced by tail vein injection of adeno-associated virus (AAVs) in spontaneously hypertensive rats (SHRs), indicating that activation of NLRP3 inflammasome accelerated hypertensive endothelial injury. ST not only protected vascular endothelial function in SHRs by inhibiting the activation of NLRP3 inflammasome and the expression of related inflammatory mediators, but also improved AngII-induced huvec injury. In summary, our results show that alleviative NLRP3 inflammasome activation attenuates hypertensive endothelial damage and ST ameliorates vascular endothelial dysfunction in hypertension via inhibiting activation of the NLRP3 inflammasome.

Abstract P391: Temporal Trends in Medical Therapies for Hospitalized ST- and Non-ST Elevation Myocardial Infarction: The Atherosclerosis Risk in Communities (ARIC) Study Community Surveillance

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Emily C O'Brien ◽  
Chris D Baggett ◽  
Alvaro Alonso ◽  
Wayne D Rosamond
Keyword(s):  
Myocardial Infarction ◽  
Ace Inhibitors ◽  
Poisson Regression ◽  
Beta Blockers ◽  
Temporal Trends ◽  
St Elevation Myocardial Infarction ◽  
Lipid Lowering ◽  
St Elevation ◽  
Medical Therapies ◽  
Aric Study

Background: Reports from large studies using administrative datasets and event registries have characterized recent temporal trends and treatment patterns for AMI. However, few are population based and fewer have examined differences in patterns of treatment for patients presenting with ST elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI). We examined 21-year trends in the use of 10 medical therapies and procedures by STEMI and NSTEMI classification in the ARIC Community Surveillance Study. Methods: We analyzed data from an estimated 30,986 definite or probable MIs between 1987 and 2008 among residents 35-74 years of age in the four geographically defined US communities of the ARIC Study. Data on medical therapies was obtained through detailed abstraction of the medical records. Classification of STEMI and NSTEMI was based on independent Minnesota coding of electrocardiograms. We used weighted Poisson regression to estimate annual proportions of patients receiving each medication or procedure and age-standardized these estimates to the 2000 U.S. Census population. We then used weighted multivariable Poisson regression controlling for sex, race/center classification, age, and PREDICT mortality risk score to estimate average annual percent changes in medical therapy use over the study period. Results: From 1987 – 2008, 6106 (19.7%) hospitalized events were classified as STEMI, and 20302 (65.5%) were classified as NSTEMI. Among STEMI patients, increases (%; 95% CI) were noted in the use of ACE inhibitors (6.4; 5.7, 7.2), non-aspirin anti-platelets (5.0; 4.0, 6.0), lipid-lowering medications (4.5; 3.1, 5.8), beta blockers (2.7; 2.4, 3.0), aspirin (1.2; 1.0, 1.3), and heparin (0.8; 0.4, 1.3). Among NSTEMI patients, the use of ACE inhibitors (5.5; 5.0, 6.1), non-aspirin anti-platelets (3.7; 2.7, 4.7), lipid-lowering medications (3.0; 1.9, 4.1), beta blockers (4.2; 3.9, 4.4), aspirin (1.9, 1.6; 2.1), and heparin (1.7; 1.3, 2.1) increased. Calcium channel blocker use decreased for both STEMI (−8.8%;−9.6,−8.0) and NSTEMI (−5.6; −6.1,−5.1) patients over the study period. Among STEMI patients, we observed decreases in the use of thrombolytics (−7.2; −7.9, −6.6) and CABG (−2.4%; −3.6, −1.2). We noted similar decreases in the use of thrombolytics (−9.8; −10.7, −8.8) and CABG (−2.5; −3.3, −1.6) among NSTEMI patients. PCI use increased for both STEMI (6.4; 5.8, 7.0) and NSTEMI (5.1; 4.5, 5.7) patients. Increases in the use of stents were documented for both STEMI (4.5; 2.7, 6.2) and NSTEMI patients (1.3; −0.5, 3.2). Conclusion: We found trends of increasing use of evidence-based medicine for both STEMI and NSTEMI patients over the past 21 years. Future research should examine the broader public health impact of increasing adherence to clinical therapy guidelines.

Therapeutic Potential of Phosphodiesterase Inhibitors for Endothelial Dysfunction- Related Diseases

2020 ◽  
Vol 26 (30) ◽  
pp. 3633-3651 ◽  
Author(s):  
Javier Blanco-Rivero ◽  
Fabiano E. Xavier
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Therapeutic Potential ◽  
Treatment Strategies ◽  
Phosphodiesterase Inhibitors ◽  
Developed Countries ◽  
Major Health Problem ◽  
Pde Inhibitors ◽  
Pharmaceutical Industries

Cardiovascular diseases (CVD) are considered a major health problem worldwide, being the main cause of mortality in developing and developed countries. Endothelial dysfunction, characterized by a decline in nitric oxide production and/or bioavailability, increased oxidative stress, decreased prostacyclin levels, and a reduction of endothelium-derived hyperpolarizing factor is considered an important prognostic indicator of various CVD. Changes in cyclic nucleotides production and/ or signalling, such as guanosine 3', 5'-monophosphate (cGMP) and adenosine 3', 5'-monophosphate (cAMP), also accompany many vascular disorders that course with altered endothelial function. Phosphodiesterases (PDE) are metallophosphohydrolases that catalyse cAMP and cGMP hydrolysis, thereby terminating the cyclic nucleotide-dependent signalling. The development of drugs that selectively block the activity of specific PDE families remains of great interest to the research, clinical and pharmaceutical industries. In the present review, we will discuss the effects of PDE inhibitors on CVD related to altered endothelial function, such as atherosclerosis, diabetes mellitus, arterial hypertension, stroke, aging and cirrhosis. Multiple evidences suggest that PDEs inhibition represents an attractive medical approach for the treatment of endothelial dysfunction-related diseases. Selective PDE inhibitors, especially PDE3 and PDE5 inhibitors are proposed to increase vascular NO levels by increasing antioxidant status or endothelial nitric oxide synthase expression and activation and to improve the morphological architecture of the endothelial surface. Thereby, selective PDE inhibitors can improve the endothelial function in various CVD, increasing the evidence that these drugs are potential treatment strategies for vascular dysfunction and reinforcing their potential role as an adjuvant in the pharmacotherapy of CVD.

Reversing Endothelial Dysfunction With ACE Inhibitors

Circulation ◽  
1996 ◽  
Vol 94 (3) ◽  
pp. 240-243 ◽  
Author(s):  
Sanjay Rajagopalan ◽  
David G. Harrison
Keyword(s):  
Endothelial Dysfunction ◽  
Ace Inhibitors

Morphilogy and Ultrastructure of in Vitro Cultures of Aortic Endothelial Cells Interacting with Antibodies

1979 ◽  
Author(s):  
S. Korach ◽  
D. Ngo
Keyword(s):  
Endothelial Cells ◽  
Cell Surface ◽  
Vascular Endothelial Cells ◽  
Intercellular Junctions ◽  
Cell Types ◽  
Endothelial Damage ◽  
Antibody Concentration ◽  
High Yields ◽  
Scanning Em

Adult pig aortas, sectioned longitudinally, were incubated in 0.1% collagenase-PBS (15 mn, 37°C). Gentle scraping of the lumenal surface resulted in high yields (3-4 x 106 cell/aorta) of viable endothelial cells, essentially devoid of other cell types by morphological and immunochemical (F VIII-antigen) criteria. Confluent monolayers were incubated for various times (5 mn to 1 wk) with decomplemented rabbit antisera raised against pig endothelial cells. Changes in cell morphology appeared to depend on antibody concentration rather than on duration of contact with antiserum. High concentrations of antiserum (5 to 20%) led to cytoplasmic shredding, bulging of cells and extensive vacuolization, whereas at lower concentrations, cells appeared almost normal. Transmission EM studies by the indirect immunoperoxydase method showed antibodies reacting with unfixed cells to be distributed all over the upper cell surface, in the outer parts of intercellular junctions, and within numerous pinocytotic vesicles. Much weaker reactions could also be seen at the lower cell surface. When viewed under the Scanning EM, antiserum-treated endothelial cells also disclosed antibody concentration-dependent bulging and release of cells from their substrate. In vitro studies of gradual modifications of vascular endothelial cells acted upon by antibodies should provide a better understanding of the structural and biochemical processes underlying endothelial damage and detachment.

The role of cardio-protective agents in breast cancer patients to prevent anthracycline induced cardiotoxicity: a systematic review and network meta-analysis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Jeyaprakash ◽  
S Sangha ◽  
K Robeldo ◽  
K Ellenberger ◽  
S Sivapathan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Ace Inhibitors ◽  
Ace Inhibitor ◽  
Beta Blockers ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Breast Cancer Patients ◽  
Protective Agents ◽  
Cardio Protection

Abstract Background Anthracycline (ANT)-based chemotherapy for breast malignancies have significantly improved cancer outcomes. However, the cardiotoxicity induced by ANTs in the breast cancer population has increased major adverse cardiac events. While randomised controlled trials (RCTs) have explored different primary preventative agents to confer cardio-protection pre chemotherapy, comparisons between agents has been limited. It is unclear which drug is the most efficacious in preserving Left Ventricular Ejection Fraction (LVEF) amongst this population. Purpose To perform a network meta-analysis of RCTs comparing the impact on LVEF of various prophylactic cardio-protective agents, when prescribed to breast cancer patients prior to ANT-based chemotherapy. Methods Two independent authors performed a literature search as per the PRISMA guidelines using four databases (CENTRAL, Cochrane Reviews, MEDLINE, SCOPUS), to find RCTS evaluating cardio protective agents. The trial population was limited to patients with breast cancer without prior ANT exposure. Trials were only included if the cardio-protective agents were commenced prior to ANT dosing. The assessed outcome was a mean change in LVEF pre and post ANT dosing, compared to placebo prevention. Extracted data included age, ANT dose, and LVEF pre and post chemotherapy. The Cochrane Risk of Bias tool was used to appraise included RCTs. Results From 2807 search results, we identified twelve RCTs which evaluated 1126 patients. Seven studies assessed beta-blockers alone and two assessed combination ACE inhibitors and beta blockers. Individual studies assessing ACE inhibitors, spironolactone or rosuvastatin alone were also included. All patients were female with an average age of 50.5 and average ANT dose of 412 mg/m2. Our network meta-analysis showed beta-blockers showed significant protection with higher LVEF than placebo by 2.38% [0.52, 4.25]. ACE inhibitors showed a similar magnitude of LVEF preservation 2.59% [−0.20, 5.38] but not statistically significant due to wider CI because of lower sample size (n=250). Spironolactone showed a statistically significant preservation in LVEF by 12.80% [3.44, 22.16], however this was based on a single study (n=83), with marked measurement bias and deviations from intended intervention. All included trials had an intermediate or high risk of bias, with marked heterogeneity in ANT dosing and LVEF monitoring. Conclusion Beta-blockers minimise LVEF decline when administered prior to anthracycline chemotherapy, compared against alternate agents. Data may be underpowered to demonstrate the benefit of ACE inhibitor and combination beta blocker/ACE inhibitor prescription. The quality of RCT data to date is limited by a high risk of bias and significant heterogeneity between RCA reporting. This analysis is likely to inform clinical practice, and allow clinicians to prescribe primary cardio-protection in patients at high risk of cardiotoxicity. Funding Acknowledgement Type of funding source: None

Abstract 135: Endothelial Dysfunction in Acute Graft-versus-host Disease After Allogeneic Hematopoietic Cell Transplantation. In vitro Evidence of the Protective Effect of Defibrotide

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Enrique Mir ◽  
Marta Palomo ◽  
Enric Carreras ◽  
Maribel Diaz-Ricart ◽  
Montse Rovira ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Protective Effect ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Endothelial Damage ◽  
Hematopoietic Cell ◽  
Graft Versus Host ◽  
Acute Graft

Acute Graft-Versus-Host Disease (aGVHD) is the most common early complication after allogeneic Hematopoietic Cell Transplantation (allo-HCT). We demonstrated endothelial dysfunction (ED) in association with allo-HCT. According to this data, aGVHD has been linked to an inflammatory process that may affect the endothelium. To investigate the differential degree of endothelial damage in patients developing or not aGVHD, to identify potential biomarkers, and to explore the protective effect of defibrotide (DF) in this scenario. DF has orphan designation for GVHD prevention. Patients blood samples were collected before allo-HCT, at day 0, and every week till day 28 after HCT. Plasma proteins (sTNFR1, sVCAM-1, VWF and ADAMTS-13) were measured as biomarkers of ED in individual samples from patients developing (GVHD, n=24), or not (NoGVHD, n=13), aGVHD. In in vitro assays, endothelial cells (EC) in culture were exposed to media containing pooled sera from patients to evaluate changes in the: a) expression of VCAM-1 and ICAM-1 on cell surfaces; b) presence of VWF on the extracellular matrix (ECM) and c) reactivity of the ECM towards platelets, under flow. The effect of DF was explored in the in vitro experiments by previous exposure of the EC (for 24h) followed by continuous incubation (100 μg/ml, added every 24h). Levels of sTNFRI, sVCAM-1 and VWF in samples from group GVHD were significantly higher than in NoGVHD (increases of 100, 37 and 150% respectively, at diagnose, p<0.01). ADAMTS-13 activity and VWF levels were inversely related. In in vitro studies, cell surface expression of VCAM-1 and ICAM-1, presence of VWF and platelet adhesion on the ECM in response to GVHD samples were always superior (increases vs NoGVHD of 80, 40, 100 and 21%, respectively, at diagnose). In vitro exposure of EC to DF attenuated signs of endothelial injury reducing significantly (p<0.05) the expression of VCAM-1, ICAM-1 and VWF (reductions of 22, 30 and 30%, respectively) in the GVHD condition. Our results demonstrate endothelial damage in association with aGVHD, as evidenced by elevated plasma levels of several biomarkers. The in vitro approach showed a marked proinflammatory and prothrombotic phenotype in association with aGVHD, which could be significantly prevented by defibrotide.

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