Vessel Endothelial Dysfunction Research Articles

Racial Disparities in Cardio-Oncology: Contributions of Anti-Cancer Therapy Induced Endothelial Dysfunction

Background: Major adverse cardiovascular (CV) events (MACE) related to anti-cancer therapy (CTx) represent the leading cause of non-cancer related mortality among breast cancer (BC) survivors. Most preclinical studies have focused on the heart, but increasing evidence suggests decreased endothelial function is predictive of CTx induced cardiac events. To date, the role of microvascular endothelial (dys)function, a well-established predictor of MACE, has been mostly ignored and few mechanistic studies exist in human subjects. CV disease in general, and CTx induced adverse events specifically, are significantly more prevalent in Black (B) relative to non-Hispanic White (NHW) patients. Despite the overwhelming clinical evidence supporting these health disparities, the underlying causes are poorly understood. Our lab and others have demonstrated that isolated vessels from human tissue samples can be used to understand the mechanisms contributing to CV disease. The overall goal of this study is to determine the effect of anti-cancer therapy on microvascular function and identify possible racial disparities. Hypothesis: Ex vivo treatment with CTx leads to impaired endothelial function, which is augmented in healthy donor vessels from B compared to NHW patients. Methods: Human adipose arterioles obtained from de-identified surgical discarded specimens of healthy B and NWH patients were used for video-microscopy. Vessels were incubated ex vivo 16–20 h with CTx (trastuzumab-TZM, doxorubicin-Dox, or paclitaxel-PTX). Response to endothelial dependent flow mediated dilation (FMD 5-100 cmH2O pressure gradient), acetylcholine (ACh; 10−9 to 10−5 M), and the endothelial independent dilator papaverine (Pap 10-4 M) were evaluated. Data are presented as %Max diameter ± SEM, N. Statistical significance was established with 2-way ANOVA RM *p<0.05. Results: Exposure to Dox decreased FMD equally in vessels from B (19±3, n=8) vs. NHW patients (29±5 n=8). The TZM induced endothelial dysfunction in vessels from B patients (37±8*, n=11) was augmented compared to NHW patients (57±15, n=6). PTX did not impair FMD in NHW patients (93±0.9, n=7) but showed a significant reduction in vessels from B patients (49±10*, n=10). Similar results were observed with ACh dilation, but Max dilator capacity to papaverine was unchanged in either group (not shown). Conclusion: Our findings suggest that racial disparities may contribute to differences in microvascular function and clinical outcomes of BC patients. Since dysfunction of the microcirculation is a common predecessor to heart failure and other MACE, novel strategies designed to predict, manage, and treat these adverse effects are needed and should be tailored to individual patient populations. To date, we cannot differentiate between biological/genetic vs. social/environmental contributors to the observed microvascular responses to CTx; that will be the focus of future studies. This work was supported by the American Heart Association Scientific Focused Research Network grant (SFRN.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

KPs improve renal function and blood vessels function by balance the sFlt-1:PlGF ratio in L-NAME-induced SHRSP preeclampsia rats

Preeclampsia (PE) is one of the major problems for global healthy burden. It affects 2 to 8% of all pregnancies and causes both maternal and infant morbidity and mortality. Kefir peptides are products from many kinds of prebiotic fermentation in whole milk by kefir grain. In this study, we used the N(ω)-nitro-L-arginine methyl ester (L-NAME) in drinking water to mimic the preeclampsia in spontaneous hypertension rat stroke-prone (SHRSP) pregnant rats, the rats were assigned to five treatment groups: the normal group, untreated group, L-NAME group, L-NAME+KPs (LD and HD dose diets) for 20-day experiment. Data showed that rats only gave the L-NAME group induced severe high blood pressure, urine protein, placenta damage, and embryo reabsorption. After KPs pre-administration significantly reduced urine protein production and generalized vessel endothelial dysfunction, anti-oxidative, and anti-inflammation levels in SHRSP rats placenta. In conclusion, kefir peptides is a multipurpose peptide that can suppress oxidative stress, HIF-1a, anti-TNF-α and IL-6 inflammation levels, reducing urine protein production and generalized vessel endothelial dysfunction and balance the sFlt-1:PlGF ratio through blocking eNOS/NO. KPs might be a promising protective nutraceutical agent for early pregnancies. The Higher Education Sprout Project by the Ministry of Education (MOE-112-S-0023) in Taiwan. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Predictors of non-obstructive coronary slow flow in poorly controlled type 2 diabetes mellitus: a cross-sectional study

BackgroundCoronary slow flow (CSF) can occur due to various factors, such as inflammation, small vessel disease, endothelial dysfunction, and inadequate glucose control. However, the exact pathological mechanisms behind CSF remain incompletely understood.The objective of this study was to identify the risk factors associated with slow coronary flow in individuals with Type 2 Diabetes Mellitus (T2DM) who have non-obstructive coronary artery disease (CAD) and experience CSF.MethodsWe conducted a prospective cohort study involving 120 patients with T2DM who were referred for invasive coronary angiography due to typical chest pain or inconclusive results from non-invasive tests for myocardial ischemia. Using a 2 × 2 design, we categorized patients into groups based on their glycemic control (adequate or poor) and the presence of CSF (yes or no), defined by a TIMI frame count > 27. All patients had non-obstructive CAD, characterized by diameter stenosis of less than 40%. We identified many variables associated with CSF.ResultsOur investigation revealed no significant differences in age, sex, family history of coronary artery disease, ECG ischemia abnormalities, or echocardiographic (ECHO) data between the groups. In patients with adequate glycemic control, hypertension increased the risk of CSF by 5.33 times, smoking by 3.2 times, while dyslipidemia decreased the risk by 0.142. Additionally, hematocrit increased the risk by 2.3, and the platelet-to-lymphocyte ratio (PLR) increased the risk by 1.053.Among patients with poor glycemic control, hematocrit increased the risk by 2.63, and the Neutrophil-to-Lymphocyte Ratio (NLR) by 24.6. Notably, NLR was positively correlated with glycemic control parameters in T2DM patients with CSF.ConclusionsIn T2DM patients with CSF, various factors strongly correlate with glycemic control parameters and can be employed to predict the likelihood of CSF. These factors encompass hypertension, smoking, increased body mass index (BMI), elevated platelet count, hematocrit, NLR, PLR, and C-reactive protein (CRP).Trial registrationRegistry: ZU-IRB (ZU-IRB#9419–3-4-2022), Registered on: 3 April 2022, Email: IRB_123@medicine.zu.edu.eg.

Interleukin-6 (IL-6) as a Marker of Endothelial Dysfunction Confirmed Using Flow Mediated Dilatation in Active Smoker

Background: The pro-inflammatory cytokine interleukin-6 (IL-6) is thought to be the catalyst for endothelial dysfunction caused by smoking. Flow-mediated dilatation (FMD) is a non-invasive method to identify the development of blood vessel endothelial dysfunction at an early stage. However, several studies have not sufficiently explained how smoking and IL-6 interact. Objective: This study focuses on the role of Interleukin-6 (IL-6) in the process of endothelial dysfunction confirmed using non-invasive modalities such as Flow Mediated Dilatation (FMD) in smokers related to the risk of cardiovascular disease in the future with the hope of providing insight in education to smokers to quit smoking. Material and Methods: In this study, we gathered 116 male participants, of which 56 were nonsmokers, and 60 were smokers, and we used IL-6 and FMD testing. SPSS for Windows version 23 will be used to analyze the data. Result: According to the analysis of laboratory tests, the average IL-6 level in light smokers was 67.7±3.2 and in moderate smokers it was 95.111.0; with a p-value of 0.009, indicating a significant difference among the groups. The average FMD in the smoking group was 5.4±0.4% (p-value 0.000), whereas the average FMD in the non-smoker samples was 10.9±0.9%. We also looked at the average FMD among light and moderate smokers based on Brinkman Index, which was 5.5±0.4% and 5.00.4%, with a p-value of 0.780, indicating no significant difference between the groups Conclusion: Compared to non-smokers, this study demonstrates a correlation between IL-6 and smoking activity. However, there was no statistically significant difference between the prevalence of endothelial dysfunction and the degree of smoking dependence in this investigation.

Маркеры эндотелиальной дисфункции у реконвалесцентов коронавирусной инфекции COVID-19

Vessel endothelial dysfunction is one of the key reasons for the development of thrombosis and unfavorable outcome in patients with COVID-19 coronavirus infection. The risk of thrombosis in patients with COVID-19 may persist during the convalescence period, after discharge from hospital. The purpose — to assess hemostatis in convalescents with moderate COVID-19. Material and methods. The study of hemostasis was conducted in 32 patients aged 40 to 79 years with coronavirus infection COVID-19 during the period of convalescence, after discharge from hospital. The control group consisted of 20 healthy people of the same age. The study included determining biomarkers of endothelial dysfunction in venous blood: P-selectin, von Willebrand factor (VWF), D-dimer and thrombomodulin. Results. It was found that in 24 of 32 patients (75%) after COVID-19 the level of D-dimer was significantly higher than in the control group. Median D-dimer was elevated even 3-4 months after discharge from hospital. P-selectin levels were elevated in 12 (37%) patients who recovered from COVID-19. The median P-selectin was higher than that of the control group 3-4 months after discharge from hospital. A decrease in thrombomodulin levels was recorded in 10 patients (31%). The parameter median was lower than that in the control group only during the first 2 months after discharge from hospital. The values of the FFB factor in patients after COVID-19 did not differ from those in the control group. Conclusion. A significant proportion of convalescents with moderate COVID-19, even 3-4 months after discharge from hospital, retain endothelial dysfunction and procoagulant potential, which causes the risk of thrombotic complications.

Functional state of the endothelium in men after mine-explosive injury during the war in Ukraine

Mine-explosive trauma (MET) is the most common trauma type and one of the main disability causes of the able-bodied contingent. Among the mechanisms of the cardiovascular and cerebrovascular disorders development after MET, endothelial dysfunction (ED) plays an important role. The study aims - to assess the functional state of the microvessels and large arteries endothelium in men after a mine-explosive injury. Materials and methods: the functional state of the skin microvessels endothelium was determined using a two-channel laser Doppler flowmeter BLF-21D "Transonic Systems Inc" (USA) during the test with the creation of reactive hyperemia. The function of the large arteries endothelium was determined using the D.S. Celermajer test, with post-occlusion reactive hyperemia according to the generally accepted method on the Nemio XG device, SSA-580A (Toshiba) with a high-frequency linear sensor with a central frequency of 7 MHz. We examined men with mild MET (average age 37.7 ± 1.5 years). The control group was represented by 43 practically healthy men without MET (average age 41.8 ± 2.1 years). Results: dysfunction of the microvessels endothelium was found in most persons with MET (69.1%), compared to men without MET (41.9%). Dysfunction of the large vessels endothelium was found in 40.4% of examined persons with MET. Persons with MET have a combination of large and small vessel endothelial dysfunction in 23.4% of cases, at the same time persons without MET have a higher proportion of isolated microvessel endothelial dysfunction (34.9%). Conclusions: men with MET often have arterial endothelial dysfunction with microvascular endothelial dysfunction together, whereas men without MET have predominantly isolated microvascular endothelial dysfunction. ________________________________________________________________________________________ Keywords: mine-explosive injury; functional state of the endothelium; microcirculation.

Association between Intestinal Microecological Changes and Atherothrombosis.

Atherosclerosis (AS) is a chronic inflammatory disease of large- and medium-sized arteries that causes ischemic heart disease, strokes, and peripheral vascular disease, collectively called cardiovascular disease (CVD), and is the leading cause of CVD resulting in a high rate of mortality in the population. AS is pathological by plaque development, which is caused by lipid infiltration in the vessel wall, endothelial dysfunction, and chronic low-grade inflammation. Recently, more and more scholars have paid attention to the importance of intestinal microecological disorders in the occurrence and development of AS. Intestinal G-bacterial cell wall lipopolysaccharide (LPS) and bacterial metabolites, such as oxidized trimethylamine (TMAO) and short-chain fatty acids (SCFAs), are involved in the development of AS by affecting the inflammatory response, lipid metabolism, and blood pressure regulation of the body. Additionally, intestinal microecology promotes the progression of AS by interfering with the normal bile acid metabolism of the body. In this review, we summarize the research on the correlation between maintaining a dynamic balance of intestinal microecology and AS, which may be potentially helpful for the treatment of AS.

Creating the Phenotype of Preeclamptic Endothelial Dysfunction in Placental Vessels

Objective: To determine if placental vessel endothelial dysfunction can be produced in control vessels by exposure to preeclamptic plasma, establishing a model to further explore the mechanisms of dysfunction and therapeutics to restore function in preeclampsia. Hypothesis: Preeclamptic plasma administered to unaffected vessels induces endothelial dysfunction. Methods: Placental microvessels were dissected from the maternal side of placentas from patients consented to the Medical College of Wisconsin Maternal Research Placenta and Cord Blood Bank. Control vessels were treated with 10% healthy maternal plasma or 10% preeclamptic (PreE) maternal plasma within the vessel lumen for 12-16 hours[MJ1]. PreE vessels were not treated with plasma. Microvessels were then cannulated on glass micropipettes, pressurized to 60mmHg and constricted with 0.1-1.0 nM Endothelin-1 (ET-1). A 1-100cm H2O pressure gradient was applied and the inner diameter of the vessel was measured by video microscopy. The change in diameter was calculated as a % of maximum diameter as assessed by exposure to 100μM papaverine. Flow mediated dilation (FMD) was evaluated by a two-way ANOVA test with Dunnett’s multiple comparisons. The maximum dilation values were evaluated by a Kruskal-Wallis test with Dunn’s multiple comparative test or t-test as appropriate. FMD is evaluated as mean +/- SEM. Data: Control vessels at maximum flow dilated to 81.1 % ± 7.1 % (n=5), whereas vessel from PreE placentas dilated to 36.9 % ± 8.6% (n=3,). Incubation of control vessels with normal plasma resulted in maximal dilation of 80.6% ± 3.3%, n=3. Control vessels incubated with plasma from PreE patients dilated to 44.7% ± 4.7%. n=3). Summary of Results: Control vessels dilated significantly more than PreE vessels when evaluated by t-test (p=0.05). Incubation of control vessels with normal plasma did not change maximal dilation (p>0.99). Control vessels incubated with PreE plasma demonstrated a near significant drop in dilatory capacity (p=0.05). PreE plasma exposed vessels compared to untreated PreE vessels showed no significant difference (p=0.46[DDG2] ).When comparing overall flow mediated dilatory responses in these vessels there is a significant difference observed between control vessels, control vessels treated with PreE plasma, and PreE vessels at 50cm H2O (p<0.05). This difference is even more significant (p<0.01) at the maximum pressure gradient when analyzed by two-way ANOVA. There is no significant difference at any point between control vessels and control vessels treated with normal plasma as evaluated by two-way ANOVA (p>0.99). Conclusions: The addition of PreE plasma to control vessels demonstrates similar impairment in endothelium-dependent vasodilation as seen in untreated PreE vessels. Future directions will include evaluation of the mechanisms of vasodilation and therapeutic options that could restore endothelial function in PreE vessels. NHLBI 1K08HL150340-01 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Protective role of 3-oxypyridine derivatives in rats’ steroid-induced osteoporosis associated with reduced oxidative stress and recovery of nitric oxide formation

From the point of view of the mechanisms for the implementation of pathogenetic links in the development of steroid-induced osteoporosis considered in the paper, the increased risk of the oxidative stress in osteoblasts, as well as the development of the vessels endothelial dysfunction of the microcirculatory bloodstream in the bone tissue, are of particular interest. They lead to the impaired bone tissue trophism and progression of osteoporosis.The aim of the study was research of the osteoprotective effects of a 3-hydroxypyridine derivatives composition on the model of steroid-induced osteoporosis.Materials and methods. To model osteoporosis pathology, the animals (male Wistar rats) were injected with methylprednisolone (MP) at the dose of 5 mg/kg (intraperitoneally) every 5th day for 5 weeks. Аs a non-selective blocker of NO synthase, L-NAME was used at the dose of 25 mg/kg (intraperitoneally). Derivatives of 3-hydroxypyridine (hereinafter referred to as composition No. 1) were administrated at the dose of 50 mg/kg (per os) In all experimental groups, the level of microcirculation and the bone mineral density, as well as the analysis of histomorphological and biochemical samples, were assessed.Results. The study results showed that composition No. 1 (50 mg/kg) has an osteoprotective activity, effectively prevents a decrease in the level of the regional bone tissue microcirculation and in the development of an endothelial dysfunction. That makes it possible to increase the bone mineral density and to slow down the thinning of bone trabeculae. In addition, composition No. 1 (50 mg/kg) reduces the production of reactive oxygen species and increases the NO bioavailability.Conclusion. The data obtained indicate that the studied composition of 3-hydroxypyridine derivatives is considered a promising compound for the prevention and treatment of steroid-induced osteoporosis.

17β-Estradiol promotes sex-specific dysfunction in isolated human arterioles.

Despite data showing that estrogen is vasculoprotective in large conduit arteries, hormone therapy (HT) during menopause has not proven to mitigate cardiovascular disease (CVD) risk. Estrogen exposure through prolonged oral contraceptive use and gender-affirming therapy can also increase cis- and trans-females' risk for future CVD, respectively. The microvasculature is a unique vascular bed that when dysfunctional can independently predict future adverse cardiac events; however, studies on the influence of estrogen on human microvessels are limited. Here, we show that isolated human arterioles from females across the life span maintain nitric oxide (NO)-mediated dilation to flow, whereas chronic (16-20 h) exposure to exogenous (100 nM) 17β-estradiol promotes microvascular endothelial dysfunction in vessels from adult females of <40 and ≥40 yr of age. The damaging effect of estrogen was more dramatic in arterioles from biological males, as they exhibited both endothelial and smooth muscle dysfunction. Furthermore, females of <40 yr have greater endothelial expression of estrogen receptor-β (ER-β) and G protein-coupled estrogen receptor (GPER) compared with females of ≥40 yr and males. Estrogen receptor-α (ER-α), the prominent receptor associated with protective effects of estrogen, was identified within the adventitia as opposed to the endothelium across all groups. To our knowledge, this is the first study to report the detrimental effects of estrogen on the human microvasculature and highlights differences in estrogen receptor expression.NEW & NOTEWORTHY Microvascular dysfunction is an independent predictor of adverse cardiac events; however, the effect of estrogen on the human microcirculation represents a critical knowledge gap. To our knowledge, this is the first study to report sex-specific detrimental effects of chronic estrogen on human microvascular reactivity. These findings may offer insight into the increased CVD risk associated with estrogen use in both cis- and trans-females.

Challenges in investigating Peripheral Vascular Disease in patients with Diabetes and Cardiovascular Diseases

Given the increasing prevalence of diabetes, with cardiovascular disease representing the principle cause of death and morbidity amongst diabetics, it is imperative that early investigation and then intervention is achieved. Diabetic patients are at increased risk of peripheral arterial disease (PAD), with an earlier onset and a more severe and diffuse manifestation often being seen. The key factors in diabetic arteriopathy include vascular smooth vessel dysfunction, inflammation, hypercoagulability and endothelial dysfunction. Moreover, the presence of PAD is a marker of generalised atherosclerosis and is a strong indicator of increased morbidity and mortality due to cardiovascular ischaemic events, with the risk of atherothrombotic events increasing in the presence of concomitant diabetes.

Assessment of vessels endothelial dysfunction by protease-activated receptors (PARs) signaling in COVID-19 patients

PAR-1-mediated the endothelial disruption that occurs in the context of thromboinflammation. In addition, PAR1 promotes a profibrotic phenotype in fibroblasts, alveolar inflammation, and apoptosis. This is an active area of research; more data are needed to clarify similarities and differences of the PARs and their modulators in Post and Critical cases of COVID-19. Such issues are especially relevant given the potential use PAR-1 as a marker of promote thrombosis and tissue injury through a proposed mechanism between inflammation and thrombosis that was reported previously. This paper would track the theoretical role of PAR-1 as a marker of promote thrombosis in COVID-19 cases by looking for the following questions: What is the Cross Talk Between Thromboinflammation and Protease-activated receptors during Post and Critical cases of COVID-19?

Novel p38 Mitogen-Activated Protein Kinase Inhibitor Reverses Hypoxia-Induced Pulmonary Arterial Hypertension in Rats.

Mitogen-activated protein kinase (MAPK) signaling is strongly implicated in cardiovascular remodeling in pulmonary hypertension (PH) and right ventricle (RV) failure. The effects of a newly designed p38 inhibitor, LASSBio-1824, were investigated in experimentally induced PH. Male Wistar rats were exposed to hypoxia and SU5416 (SuHx), and normoxic rats were used as controls. Oral treatment was performed for 14 days with either vehicle or LASSBio-1824 (50 mg/kg). Pulmonary vascular resistance and RV structure and function were assessed by echocardiography and catheterization. Histological, immunohistochemical and Western blot analysis of lung and RV were performed to investigate cardiovascular remodeling and inflammation. Treatment with LASSBio-1824 normalized vascular resistance by attenuating vessel muscularization and endothelial dysfunction. In the heart, treatment decreased RV systolic pressure, hypertrophy and collagen content, improving cardiac function. Protein content of TNF-α, iNOS, phosphorylated p38 and caspase-3 were reduced both in lung vessels and RV tissues after treatment and a reduced activation of transcription factor c-fos was found in cardiomyocytes of treated SuHx rats. Therefore, LASSBio-1824 represents a potential candidate for remodeling-targeted treatment of PH.

The brachial-ankle pulse wave velocity is a predictive factor for erectile dysfunction in patients with benign prostate hyperplasia

ABSTRACT Introduction Phosphodiesterase (PDE) 5 inhibitors induce relaxation of endothelial cells. Tadalafil, one of PDE 5 inhibitors, has been applied for the treatments of erectile dysfunction (ED) and benign prostate hyperplasia (BPH). Under continuous treatments with PDE 5 inhibitor for BPH, it is significant to investigate the relationship between endothelial and sexual functions by comparing the brachial-ankle pulse wave velocity (baPWV).and the sexual health inventory for men (SHIM) score. Objectives Total 89 BPH patients who consulted our clinic with a complaint of urinary symptoms were enrolled in this prospective study. They were treated with a daily dose of 5mg tadalafil. Methods The Institutional Review Board (IRB) approved this clinical study and informed consents had been obtained from 89 BPH patients. Their vessels endothelial function was assessed by baPWV and erectile function was evaluated by SHIM score. International prostate symptom score (IPSS) was obtained as male lower urinary symptoms (LUTS) parameters. However, we focused on the relationship between vessels endothelial and erectile function in this sub-analysis report. Therefore, the SHIM scores were compared with baPWV and IPSS at 0, 3, 6, 12, 24, 36, 48, 60, 72 and 84 months after PDE5 inhibitor treatment. Results The mean age of 89 patients was 66.7 +/- 11.1 years old. Their prostate size was 29.8 +/- 21.2 ml. Initial SHIM, baPWV and IPSS score were 7.4 +/- 5.6, 1742.5 +/- 393.0 cm/sec and 17.5+/- 7.5, respectively. Before tadalafil treatment, baPWV and SHIM were significantly correlated (p=0.0025) which indicated patients with low vessels endothelial function vessels endothelial function suffered from erectile dysfunction. F4rthere06re, all the data of baPWV and SHIM including after tadalafil treatment from 3 to 84 months (n=472) were significantly co-related each other (p&amp;lt;0.0001). On the other hand, baPWV were significantly improved from 3 to12 months after tadalafil administration, however baPWV levels returned to the baseline levels after 24 to 84 months. SHIM score was significantly improved from 3 to24 months after tadalafil administration, however SHIM levels returned to the baseline levels after 36 to 84 months. Conclusions Our previous paper (Aging Male 21, 2018) reported that PDE5 inhibitors improved ED, male LUTS and baPWV from 3 to 12 months. The present data also suggested that endothelial function and male LUTS strongly related to ED in BPH patients. However, baPWV and SHM score levels returned to the baseline levels after 24 and 36 months, respectively. Thus, tadalafil can delay vessels endothelial and erectile dysfunction in BPH patients. In addition, erectile dysfunction seems to be occurred after vessels endothelial dysfunction. Hence, baPWV might be a predictive factor for ED in BPH patients with tadalafil treatments. Disclosure Work supported by industry: no.

Endothelial (Dys)function in Women With Androgen Excess Polycystic Ovary Syndrome: Effects of Body Composition and Ethinyl Estradiol Supplementation

Polycystic ovary syndrome (PCOS) has been associated with endothelial dysfunction. However, whether endothelial dysfunction occurs as a result of obesity in androgen excess PCOS (AE‐PCOS) remains unclear. The purpose of this study was to compare endothelial function between lean and overweight/obese (OW/OB) women with AE‐PCOS. We hypothesis that OW/OB women with AE‐PCOS would demonstrate impaired endothelial function relative to lean women with AE‐PCOS as well as both lean and OW/OB controls without any form of PCOS. We also tested the hypothesis that short‐term ethinyl estradiol (EE) supplementation improves endothelial function in both lean and OW/OB women with AE‐PCOS. We assessed conduit vessel endothelial function in 14 women with AE‐PCOS (lean: n=7; OW/OB: n=7) and 12 controls (CTRL; lean: n=6, OW/OB: n=6) using flow‐mediated dilation (FMD). FMD responses were assessed twice: before (baseline; BSL) and on the last day of 7‐day oral EE (post‐EE; 30mg/day) and quantified as the peak increase in diameter during reactive hyperemia (%FMD), shear rate, and low flow‐mediated vasoconstriction (LFMC). BSL %FMD was attenuated in lean AE‐PCOS relative to both lean CTRL (5.2 ± 1.5% vs10.3 ± 2.6%, P&lt;0.01) and OW/OB AE‐PCOS (5.2 ± 1.5% vs6.6 ± 0.9%, P=0.04). A negative correlation between BSL %FMD and free testosterone was observed in lean AE‐PCOS only (R2=0.68, P=0.02). %FMD was unchanged from BSL to post‐EE in lean AE‐PCOS (5.17±1.5 vs5.17±1.1, P=0.99). Post‐EE, %FMD was lower in lean CTRL (10.3±2.6% vs7.6±1.2%, P=0.03), but increased in both OW/OB CTRL (7.3±0.1.2% vs 10.4±2.5%) and OW/OB women with AE‐PCOS (6.6±0.92% vs 9.6±1.7%; main effect of EE, P&lt;0.01). Post‐EE %FMD changes from BSL were associated with EE‐induced changes in LFMC and shear rate. Our data indicate that lean women with AE‐PCOS exhibit more severe conduit vessel endothelial dysfunction than OW/OB women with AE‐PCOS. Our data also indicate that short‐term EE supplementation affects LFMC and shear rate (and therefore %FMD) differently across healthy lean women and OW/OB women with and without AE‐PCOS.

Pathomechanisms of Vascular Depression in Older Adults.

Depression in older individuals is a common complex mood disorder with high comorbidity of both psychiatric and physical diseases, associated with high disability, cognitive decline, and increased mortality The factors predicting the risk of late-life depression (LLD) are incompletely understood. The reciprocal relationship of depressive disorder and age- and disease-related processes has generated pathogenic hypotheses and provided various treatment options. The heterogeneity of depression complicates research into the underlying pathogenic cascade, and factors involved in LLD considerably differ from those involved in early life depression. Evidence suggests that a variety of vascular mechanisms, in particular cerebral small vessel disease, generalized microvascular, and endothelial dysfunction, as well as metabolic risk factors, including diabetes, and inflammation that may induce subcortical white and gray matter lesions by compromising fronto–limbic and other important neuronal networks, may contribute to the development of LLD. The “vascular depression” hypothesis postulates that cerebrovascular disease or vascular risk factors can predispose, precipitate, and perpetuate geriatric depression syndromes, based on their comorbidity with cerebrovascular lesions and the frequent development of depression after stroke. Vascular burden is associated with cognitive deficits and a specific form of LLD, vascular depression, which is marked by decreased white matter integrity, executive dysfunction, functional disability, and poorer response to antidepressive therapy than major depressive disorder without vascular risk factors. Other pathogenic factors of LLD, such as neurodegeneration or neuroimmune regulatory dysmechanisms, are briefly discussed. Treatment planning should consider a modest response of LLD to antidepressants, while vascular and metabolic factors may provide promising targets for its successful prevention and treatment. However, their effectiveness needs further investigation, and intervention studies are needed to assess which interventions are appropriate and effective in clinical practice.

Arsenic exposure promotes the emergence of cardiovascular diseases

A large number of studies conducted in the past decade 2010-2020 refer to the impact of arsenic (As) exposure on cardiovascular risk factors. The arsenic effect on humans is complex and mainly depends on the varying individual susceptibilities, its numerous toxic expressions and the variation in arsenic metabolism between individuals. In this review we present relevant data from studies which document the association of arsenic exposure with various biomarkers, the effect of several genome polymorphisms on arsenic methylation and the underling molecular mechanisms influencing the cardiovascular pathology. The corresponding results provide strong evidence that high and moderate-high As intake induce oxidative stress, inflammation and vessel endothelial dysfunction that are associated with increased risk for cardiovascular diseases (CVDs) and in particular hypertension, myocardial infarction, carotid intima-media thickness and stroke, ventricular arrhythmias and peripheral arterial disease. In addition, As exposure during pregnancy implies risks for blood pressure abnormalities among infants and increased mortality rates from acute myocardial infarction during early adulthood. Low water As concentrations are associated with increased systolic, diastolic and pulse pressure, coronary heart disease and incident stroke. For very low As concentrations the relevant studies are few. They predict a risk for myocardial infarction, stroke and ischemic stroke and incident CVD,but they are not in agreement regarding the risk magnitude.

Vasoplegia from Continuous Flow Left Ventricular Assist Devices.

The contribution of continuous flow left ventricular assist devices (c-LVAD) to vasoplegic syndrome and postoperative outcomes after orthotopic heart transplant (OHT) is contested in the literature. A standardized definition of vasoplegic syndrome (VS) is needed to better recognize and manage vasoplegic shock. Vasoplegic syndrome occurs after orthotopic heart transplant more frequently than after other surgeries requiring cardiopulmonary bypass. c-LVADs lead to small vessel endothelial dysfunction and desensitized adrenal receptors; however, their contribution to the development of vasoplegia is debated in clinical studies. Pulsatility may mitigate vascular dysfunction resulting from long-term continuous flow, and should be further explored in the clinical setting when considering risk factors for vasoplegic syndrome. The incidence of vasoplegic syndrome after orthotopic heart transplant is rising with the increasing use of c-LVAD bridge to therapy. Robust clinical studies are needed to advance our understanding and approach to mitigating VS after OHT.

Exercise Electrocardiography Testing in Patients with Calcific Non-obstructive Coronary Lesions at Cardiac Multislice Computed Tomography

Background: Non-obstructive coronary artery disease (NoCAD), cardiac syndrome X (CSX), conduit vessel endothelial dysfunction and microvascular angina are all terms used to describe patients that have chest pain yet no obstructive coronary artery disease on coronary angiography. Objectives: the purpose of this study was to evaluate exercise ECG (Ex-ECG) test in patients with subclinical atherosclerosis who were diagnosed by multi-slice computed tomography (MSCT) coronary angiography to have nonobstructive lesions. Patients and Methods: 100 patients were recruited in the current study (their age ranged from 30 – 66 years), they were classified into three groups: group (A) 30 patients with non-calcific normal coronaries by MSCT, group (B) 35 patients with non-calcific non-obstructive lesions (zero calcium score) by MSCT and group (C) 35 patients with calcific non-obstructive lesions (calcium score < 400 HU) by MSCT. Results: There was statistically highly significant difference between the three groups as regard results of exercise ECG test (P value=0.001). Positive exercise ECG test results occurred with calcific and mixed plaques in group (C) more than soft plaque in group (B), and there is significant difference between two groups with (P-value = 0.001). Positive exercise ECG test results in group (C) occurred more frequently with higher calcium score ranged from (59 – 362) HU. Conclusions: MSCT angiography and calcium scoring system can provide valuable results which is helpful in avoiding an extra unnecessary invasive coronary angiography in patients for whom exercise ECG test results seemed to be positive or for whom high cardiovascular mortality risk from ischemia is not present.

Exercise Electrocardiography Testing in Patients with Calcific Non-obstructive Coronary Lesions at Cardiac Multislice Computed Tomography

Background: Non-obstructive coronary artery disease (NoCAD), cardiac syndrome X (CSX), conduit vessel endothelial dysfunction and microvascular angina are all terms used to describe patients that have chest pain yet no obstructive coronary artery disease on coronary angiography. Objectives: the purpose of this study was to evaluate exercise ECG (Ex-ECG) test in patients with subclinical atherosclerosis who were diagnosed by multi-slice computed tomography (MSCT) coronary angiography to have nonobstructive lesions. Patients and Methods: 100 patients were recruited in the current study (their age ranged from 30 – 66 years), they were classified into three groups: group (A) 30 patients with non-calcific normal coronaries by MSCT, group (B) 35 patients with non-calcific non-obstructive lesions (zero calcium score) by MSCT and group (C) 35 patients with calcific non-obstructive lesions (calcium score < 400 HU) by MSCT. Results: There was statistically highly significant difference between the three groups as regard results of exercise ECG test (P value=0.001). Positive exercise ECG test results occurred with calcific and mixed plaques in group (C) more than soft plaque in group (B), and there is significant difference between two groups with (P-value = 0.001). Positive exercise ECG test results in group (C) occurred more frequently with higher calcium score ranged from (59 – 362) HU. Conclusions: MSCT angiography and calcium scoring system can provide valuable results which is helpful in avoiding an extra unnecessary invasive coronary angiography in patients for whom exercise ECG test results seemed to be positive or for whom high cardiovascular mortality risk from ischemia is not present.