Endothelial Dysfunction In Women Research Articles

Regulation of MMP-2 by IL-8 in Vascular Endothelial Cells: Probable Mechanism for Endothelial Dysfunction in Women with Preeclampsia.

Endothelial dysfunction (ED) in preeclampsia (PE) results from the convergence of oxidative stress, inflammation, and alterations in extracellular matrix components, affecting vascular tone and permeability. The molecular network leading to ED includes IL-8 and MMP-2. In vitro, IL-8 regulates the concentration and activity of MMP-2 in the trophoblast; this interaction has not been studied in endothelial cells during PE. We isolated human umbilical vein endothelial cells (HUVECs) from women with healthy pregnancies (NP, n = 15) and PE (n = 15). We quantified the intracellular concentration of nitric oxide and reactive oxygen species with colorimetric assays, IL-8 with ELISA, and MMP-2 with zymography and using an ELISA-type system. An IL-8 inhibition assay was used to study the influence of this cytokine on MMP-2 concentration and activity. HUVECs from women with PE showed significantly higher oxidative stress than NP. IL-8 and MMP-2 were found to be significantly elevated in PE HUVECs compared to NP. Inhibition of IL-8 in HUVECs from women with PE significantly decreased the concentration of MMP-2. We demonstrate that IL-8 is involved in the mechanisms of MMP-2 expression in HUVECs from women with PE. Our findings provide new insights into the molecular mechanisms regulating the ED distinctive of PE.

Endogenous estradiol contributes to vascular endothelial dysfunction in premenopausal women with type 1 diabetes

BackgroundEndogenous estrogen is cardio-protective in healthy premenopausal women. Despite this favorable action of estrogen, animal models depict a detrimental effect of estradiol on vascular function in the presence of diabetes. The present study sought to determine the role of endogenous estradiol on endothelial function in women with type 1 diabetes.Method32 women with type 1 diabetes (HbA1c = 8.6 ± 1.7%) and 25 apparently healthy women (HbA1c = 5.2 ± 0.3%) participated. Flow-mediated dilation (FMD), a bioassay of nitric-oxide bioavailability and endothelial function was performed during menses (M) and the late follicular (LF) phase of the menstrual cycle to represent low and high concentrations of estrogen, respectively. In addition, a venous blood sample was collected at each visit to determine circulating concentrations of estradiol, thiobarbituric acid reactive substances (TBARS), and nitrate/nitrite (NOx), biomarkers of oxidative stress and nitric oxide, respectively. Data were collected in (1) 9 additional women with type 1 diabetes using oral hormonal birth control (HBC) (HbA1c = 8.3 ± 2.1%) during the placebo pill week and second active pill week, and (2) a subgroup of 9 demographically matched women with type 1 diabetes not using HBC (HbA1c = 8.9 ± 2.1%).ResultsOverall, estradiol was significantly increased during the LF phase compared to M in both type 1 diabetes (Δestradiol = 75 ± 86 pg/mL) and controls (Δestradiol = 71 ± 76 pg/mL); however, an increase in TBARS was only observed in patients with type 1 diabetes (ΔTBARS = 3 ± 13 µM) compared to controls (ΔTBARS = 0 ± 4 µM). FMD was similar (p = 0.406) between groups at M. In addition, FMD increased significantly from M to the LF phase in controls (p = 0.024), whereas a decrease was observed in type 1 diabetes. FMD was greater (p = 0.015) in patients using HBC compared to those not on HBC, independent of menstrual cycle phase.ConclusionEndogenous estradiol increases oxidative stress and contributes to endothelial dysfunction in women with diabetes. Additionally, HBC use appears to be beneficial to endothelial function in type 1 diabetes.

Pravastatin reduces plasma levels of extracellular vesicles in pregnancies at high risk of term preeclampsia.

Introduction: Elevated plasma levels of extracellular vesicles have been associated with impaired placentation, angiogenesis imbalance, intravascular inflammation, and endothelial dysfunction in women with preeclampsia, thus suggesting that circulating vesicles may be a good therapeutic target for the treatment of the disease. Recently, statins have been considered a potential treatment for the prevention of preeclampsia because of their pleiotropic effects, including the improvement of endothelial dysfunction and inhibition of inflammatory responses. However, the effects of these drugs on circulating vesicles concentration in women at risk of preeclampsia have not been established. Herein, we aimed to assess the effects of pravastatin on circulating extracellular vesicle generation in women at high risk of term preeclampsia. Methods: In a sample of 68 singleton pregnant women participating in the multicenter, double-blind, placebo-controlled STATIN trial (Nº EducraCT 2016-005206-19 ISRCTN), 35 women received a placebo and 33 women received a 20mg/day dose of pravastatin for approximately 3weeks (from 35 to 37weeks of gestation until delivery). Large extracellular vesicles were characterized and quantified by flow cytometry using annexin V and cell-specific antibodies directed against platelet, endothelial, leukocyte, and syncytiotrophoblast cell surface markers. Results: In women who received the placebo, a significant increase in the plasma levels of large extracellular vesicles from platelets (34%, p < 0.01), leukocytes (33%, p < 0.01), monocytes (60%, p < 0.01), endothelial cells (40%, p < 0.05), and syncytiotrophoblast cells (22%, p < 0.05) were observed. However, treatment with pravastatin significantly reduced the plasma levels of large extracellular vesicles from platelets (42%, p < 0.001), leukocytes (25%, p < 0.001), monocytes (61%, p < 0.001), endothelial cells (69%, p < 0.001), activated endothelial cells (55%, p < 0.001), and syncytiotrophoblast cells (44%, p < 0.001). Discussion: These results indicate that pravastatin reduces the levels of activated cell-derived membrane vesicles from the maternal vasculature, blood, and placental syncytiotrophoblast of women at high risk of term preeclampsia, suggesting that this statin may be beneficial in reducing endothelial dysfunction and pro-inflammatory and pro-coagulatory state characteristics of the disease.

Improving nitric oxide bioavailability to treat endothelial dysfunction in women with type 1 diabetes: impact of race

BACKGROUND: Type 1 diabetes (T1D) is associated with a greater risk of cardiovascular disease (CVD), mediated in part, by impaired nitric oxide (NO) bioavailability and endothelial dysfunction. In fact, women with T1D have a greater risk of CVD compared to men, and although the incidence of T1D is greater in Caucasians (Cs), African Americans (AAs) with T1D have significantly worse health outcomes. In healthy women, both resveratrol (RES) and antioxidants have been used to improve NO bioavailability and endothelial function by reducing oxidative stress. Accordingly, the present investigation sought to determine the role of resveratrol and antioxidants on vascular function in C and AA women with T1D. METHODS: 15 C women with T1D and 6 AA women with T1D were enrolled. Participants were randomized to either an acute dose of RES or an antioxidant cocktail (AOC) containing Vitamin C, Vitamin E, and Alpha-Lipoic Acid. The flow-mediated dilation (FMD) test, a bioassay of NO bioavailability, was utilized to assess endothelial function normalized for shear (FMD/Shear) before and after treatment. In addition, a venous blood sample was collected to assess baseline clinical laboratory values and plasma concentrations of oxidative stress (8-isoprostane (8-iso) and superoxide dismutase (SOD)) before and after treatment. Data are reported as mean ± SD. RESULTS: No differences in baseline demographics were observed between Cs and AAs. Clinical laboratory values were similar between groups, except HbA1c was higher ( p=0.013) in AAs (9.6±1.2%) compared to Cs (7.7±1.5%). Using a mixed model repeated measures design, a significant race x treatment x time interaction ( p=0.050) was observed for FMD/Shear. Treatment with AOC in AAs resulted in a significant increase ( p=0.002) in FMD/Shear. In addition, FMD/Shear was higher ( p=0.019) in AAs following treatment with AOC (0.370±0.128) compared to RES (0.212±0.049). Further, the % increase in FMD/Shear following treatment with AOC was greater ( p&lt;0.001) in AAs (48±32%) compared to Cs (-1±42%). Independent of treatment, SOD was higher at both baseline ( p&lt;0.001) and after treatment ( p=0.015) in AAs compared to Cs. Additionally, there was a decrease in SOD over time in AAs, collapsing treatment ( p=0.005). No differences in 8-iso were observed. CONCLUSION: Findings from the present investigation have identified that treatment to improve endothelial function in T1D can be race dependent. Compared to RES, treatment with AOC in AA women with T1D may be more effective at improving endothelial function. Neither treatment was effective at improving endothelial function in C women with T1D. Differences in oxidative stress may play a role; however, future studies are needed to understand how race impacts the treatment response in women with T1D. 1R01HL137087 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.

КОНТРАЦЕПЦИЯ ПОСЛЕ АБОРТА: ЭФФЕКТИВНОСТЬ И БЕЗОПАСНОСТЬ

It is important to choose a combined oral contraceptive (COC) after an abortion operation, since the requirements for a contraceptive prescribed during this period have their own specifics. It is necessary to stop as many negative consequences for the woman's body caused by the termination of pregnancy and, in addition, to ensure maximum safety of the prescribed drug. The relevance of this topic is due to the need to choose the safest and most effective contraceptive. A study was conducted of the effect of monophasic low-dose COCs, which is a combination of 0.15 mg levonorgestrel and 0.03 mg eeinylestradiol 0.03 mg in each tablet (PlaniGenslevo) on the state of the body and endothelial function in 22 women of reproductive age using the drug for 3 months after an artificial abortion and belonging to the first category of acceptability of COCs. As a control, the results of a test with reactive hyperemia were evaluated in 22 healthy women aged 19 to 35 years. As a result of the study, there was no increase in body mass index, blood pressure, changes in metabolic parameters in the biochemical analysis of blood, as well as an increase in the duration of menstrual bleeding, the absence of intermenstrual bleeding, as well as breast swelling, headaches, dyspeptic phenomena and other adverse events that may be caused by taking COCs in women using Women's Left within 3 months. The conducted study demonstrated the absence of adverse events on the part of the body of women taking after abortion Plani Women left. In addition, there were no statistically significant changes compared to the control group in the results of the test with reactive hyperemia, reflecting the absence of endothelial dysfunction in women using the contraceptive Plani Women left, which can serve as confirmation of the absence of a negative effect of the drug on the cardiovascular system.

Impact of metabolic therapy on the state of cerebral hemodynamics in hypoestrogenemia

Objective. To investigate the impact of therapy with Mildronate® on the state of cerebral hemodynamics, on vascular wall remodeling and endothelial dysfunction in women with hypertension and estradiol deficiency. Subjects and methods. The investigation enrolled 37 patients (mean age, 43.0±3.5 years) with Stage I–II hypertension, reduced estradiol and elevated follicle-stimulating hormone (FSH) levels, who formed a study group. The patients in this group received Mildronate® in addition to standard therapy. A control group consisted of 38 healthy women (mean age 43.5±3.4 years) without chronic diseases affecting intracardiac and cerebral hemodynamics. Complete medical histories were taken from all the patients who underwent a mandatory laboratory test (including estradiol and FSH levels), ECG, and duplex scanning of the great cerebral arteries. Results. The features of vascular bed remodeling, the state of cerebral hemodynamics, and endothelial dysfunction in the examinees can assume that hypoestrogenemia may be a factor contributing to the progression of hypertension and the development of complications, such as cerebrovascular accidents. Conclusion. The study results have shown that Mildronate® is well tolerated by patients and is an effective treatment, showing a positive therapeutic effect on endothelium-dependent vascular relaxation, vascular remodeling, and whole-brain hemodynamics.

THE NON-INVASIVE ASSESSMENT OF PERIPHERAL MICROVASCULAR AND ENDOTHELIAL FUNCTION IN WOMEN WITH NON-OBSTRUCTIVE CORONARY ARTERY DISEASE

THE NON-INVASIVE ASSESSMENT OF PERIPHERAL MICROVASCULAR AND ENDOTHELIAL FUNCTION IN WOMEN WITH NON-OBSTRUCTIVE CORONARY ARTERY DISEASE

Role of BH4 deficiency as a mediator of oxidative stress-related endothelial dysfunction in menopausal women.

Endothelial function (brachial artery flow-mediated dilation [FMD]) is reduced in estrogen-deficient postmenopausal women, mediated, in part, by reduced nitric oxide (NO) bioavailability, secondary to tetrahydrobiopterin (BH4) deficiency and oxidative stress. FMD is increased, but not fully restored, in postmenopausal women after acute intravenous vitamin C (VITC; superoxide scavenger) or oral BH4 supplementation. In vitro studies demonstrate that coadministration of VITC with BH4 prevents endothelial nitric oxide synthase (eNOS) uncoupling and reductions in NO by peroxynitrite. To investigate mechanisms of endothelial dysfunction in women, we assessed the separate and combined effects of VITC and BH4 to determine whether coadministration of VITC + BH4 improves FMD in healthy postmenopausal women (n = 19, 58 ± 5 yr) to premenopausal (n = 14, 36 ± 9 yr) levels, with exploratory testing in perimenopausal women (n = 8, 51 ± 3 yr). FMD was measured during acute intravenous infusions of saline (control) and VITC (∼2-3 g) ∼3 h after a single dose of oral BH4 (KUVAN, 10 mg/kg body wt) or placebo (randomized crossover, separated by ∼1 mo). Under the placebo condition, FMD was reduced in postmenopausal compared with premenopausal women during the saline infusion (5.6 ± 0.7 vs. 11.6 ± 0.9%, P < 0.001) and increased in postmenopausal women during VITC (+3.5 [1.4, 5.6]%, P = 0.001) and acute BH4 (+1.8 [0.37, 3.2]%, P = 0.01) alone. Coadministration of VITC + BH4 increased FMD in postmenopausal women (+3.0 [1.7, 4.3]%, P < 0.001), but FMD remained reduced compared with premenopausal women (P = 0.02). Exploratory analyses revealed that VITC + BH4 did not restore FMD in perimenopausal women to premenopausal levels (P = 0.045). Coadministration of VITC + BH4 does not restore FMD in menopausal women, suggesting that additional mechanisms may be involved.NEW & NOTEWORTHY Endothelial function is reduced across the menopausal stages related to increased oxidative stress associated with estrogen deficiency. In vitro studies demonstrate that coadministration of VITC with BH4 prevents endothelial nitric oxide synthase (eNOS) uncoupling and reductions in NO by peroxynitrite; however, this remains untested in humans. We demonstrate that the coadministration of BH4 + VITC does not restore endothelial function in perimenopausal and postmenopausal women to the level of premenopausal women, suggesting that other mechanisms contribute.

Optimization of the prevention of perinatal pathology in women with gestational endotheliopathy

Objectives: to evaluate the clinical effectiveness of the Metida for the prevention of perinatal pathology in pregnant women with gestational endotheliopathy and with the risk of preeclampsia.Materials and methods. 68 pregnant women with verified gestational endotheliopathy and with risk of preeclampsia &gt; 1:150 participated in a prospective clinical comparative study. The patients were divided into subgroups: the first subgroup included 30 women who from 11–13 weeks of pregnancy received acetylsalicylic acid 100 mg/day and vitamin D 2000 IU/day; the II subgroup included 38 pregnant women who from 11–13 weeks of gestation received acetylsalicylic acid 100 mg/day, vitamin D 2000 IU/day and Metida (300 mg of elemental magnesium, 30 mg of vitamin B6). 28 practically healthy pregnant women of the control group received vitamin D 1000 IU/day. The clinical effectiveness of therapy was evaluated by comparing the number of cases of perinatal pathology; cases of intrauterine suffering of the fetus; the dynamics of indicators of laboratory-instrumental research methods (markers of the risk of perinatal pathology) and the pregnancy outcomes.Results. Metida as an additional preventive therapy made it possible to significantly reduce the number of cases of placental dysfunction (р = 0.01) and intrauterine suffering of the fetus (р = 0.02) compared to standard preventive therapy. There was also a 6-fold reduction in the incidence of preeclampsia and premature birth due to magnesium supplementation, compared to pregnant women who received only acetylsalicylic acid and vitamin D. There was a significant decrease in serum indicators of markers of endothelial dysfunction in women with gestational endotheliopathy as a result of taking magnesium: vascular endothelial growth factor (p &lt; 0.00001), endoglin (p &lt; 0.00001) compared to patients who did not receive magnesium, and there was also normalization of the of 25(OH)D level in blood serum compared to the control group (p = 0.33).Conclusions. Additional Mg supplementation during pregnancy may reduce the likelihood of perinatal pathology in high-risk patients and help normalize serum markers of endothelial dysfunction in women with high risk of preeclampsia.

Oxidative Stress Contributes to Microvascular Endothelial Dysfunction in Women With a History of Gestational Diabetes

Women with a history of gestational diabetes mellitus (GDM) are twice as likely to develop cardiovascular disease as their age‐matched counterparts. GDM is associated with endothelial dysfunction and elevated oxidative stress during pregnancy, and vascular dysfunction postpartum. However, the mechanism(s) mediating this postpartum dysfunction are unknown. Using the cutaneous circulation as a model, we examined if oxidative stress contributes to microvascular dysfunction in healthy women with a history of GDM (GDM). We hypothesized that: 1) endothelium‐ and nitric oxide (NO)‐dependent dilation would be attenuated in GDM compared to women with a history of normal pregnancy (NP), and 2) local antioxidant (L‐ascorbate) administration would augment endothelium‐ and NO‐dependent dilation in GDM. Ten NP (35±1yrs) and 10 GDM (34±1yrs) underwent a standard local heating protocol (42°C; 0.1°C·s‐1). Two intradermal microdialysis fibers were placed in the ventral forearm for local delivery of lactated Ringer’s (control), or 5mM ascorbate. After full expression of the local heating response, 15mM NG‐nitro‐L‐arginine methyl ester (L‐NAME; NO synthase‐inhibition) was perfused. Red cell flux was measured continuously by laser‐Doppler flowmetry and cutaneous vascular conductance (CVC=flux/MAP) was standardized to maximum (%CVCmax; 28mM SNP + 43°C). Urine albumin to creatinine ratio (ACR) and plasma concentrations of oxidized LDL (oxLDL) and thiobarbituric acid reactive substances (TBARS) were measured. Women with history of GDM had attenuated endothelium‐dependent (GDM: 67±7 vs. NP: 90±4%CVCmax; p&lt;0.001) and NO‐dependent (GDM: 54±7 vs. NP: 71±3%; p=0.001) dilation at the control site and tended to have higher urine ACR (p=0.06). Both endothelium‐dependent (r2=0.53, p=0.02) and NO‐dependent (r2=0.56, p=0.01) dilation were related to urine ACR in GDM. Local ascorbate perfusion improved endothelium‐dependent (82±5%CVCmax; p=0.03 vs. control) and NO‐dependent (68±5%; p=0.02 vs. control) dilation in those with history of GDM but had no effect in HC (p&gt;0.05). There were no differences in plasma oxLDL (hxGDM:60.5 vs hxNP:50.9 U/L; p=0.18) or TBARS (hxGDM: 0.3 vs hxNP: 0.2 μM; p=0.26) concentrations between groups. These data suggest that otherwise healthy women with a history of GDM have attenuated microvascular endothelial function and that this dysfunction is mediated, in part, by oxidative stress at the level of the vasculature.

A single dose of dietary nitrate supplementation protects against endothelial ischemia-reperfusion injury in early postmenopausal women.

The onset of menopause and accompanying changes to ovarian hormones often precedes endothelial dysfunction in women. In particular, accelerated impairments in macrovascular and microvascular function coincide with the loss of estrogen, as does impaired endothelial responses to ischemia-reperfusion (IR) injury. In healthy, early postmenopausal women (n=12; 3.9± 1.5 years since menopause) we tested the hypothesis that acute dietary nitrate (NO3-) supplementation would improve endothelial function and attenuate the magnitude of endothelial dysfunction following whole-arm IR in comparison with placebo. In this randomized, double-blind, placebo-controlled, crossover study we tested participants before and after NO3--rich (BRnitrate) and NO3--depleted (BRplacebo) beetroot juice (BR) consumption, as well as following IR injury, and 15min after IR to assess recovery. Analyses with repeated-measures general linear models revealed a condition× time interaction for brachial artery flow-mediated dilation (FMD; P=0.04), and no interaction effect was found for the near-infrared spectroscopy-derived reperfusion slope (P=0.86). Follow-up analysis showed a significant decline in FMD following IR injury with BRplacebo in comparison with all other timepoints (all, P<0.05), while this decline was not present with BRnitrate (all, P>0.05). Our findings demonstrate that a single dose of dietary NO3- minimizes IR-induced macrovascular endothelial dysfunction in healthy, early postmenopausal women, but does not improve resting macrovascular and microvascular function. Trial registration number: NCT03644472. Novelty: In healthy, early postmenopausal women, a single dose of NO3--rich BR can protect against IR-induced endothelial dysfunction. This protection may be due to nitric oxide bioactivity during IR rather than improved endothelial function prior to the IR protocol per se.

Effects of inulin-type fructans with different degrees of polymerization on inflammation, oxidative stress and endothelial dysfunction in women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial.

Polycystic ovary syndrome (PCOS) is associated with several cardiovascular risk factors. Prebiotics were proposed to beneficially affect risk factors associated with metabolic disorders. The aim of this study was to investigate and compare the effects of inulin-type fructans (ITFs), as well-studied prebiotics, with different degrees of polymerization, on markers of inflammation, oxidative stress and endothelial dysfunction in PCOS patients. A randomized, double-blind, placebo-controlled trial. Seventy-fivePCOS women were randomly assigned to receive 10 g/day of either high-performance inulin (HPI) or oligofructose-enriched inulin (OEI) or placebofor 12 weeks. Biochemical indices and blood pressure levelswere assessed before and after the intervention. In the intent-to-treat analysis, high-sensitive C-reactive protein (hs-CRP) decreased in HPI and OEI groups, over the 12 weeks, and the changes were significant in the HPI group, compared to placebo (changes from baseline in the HPI group: -0.11 vs. placebo group: 0.004 mg/L [conversion factor to SI units (nmol/L): 9/5238]; p = .007). Serum levels of nitric oxide (NO) increased, and endothelin-1and total oxidant statusdecreased in HPI and OEI groups, at the end of the trial; however, these changes were not significantly compared to placebo (p = .07, .36 and .22, respectively). No differences in systolic and diastolic blood pressure were found. Per-protocol analysis (n = 68) yielded consistent results for all endpoints, with the exception that the significant effect of ITFs on serum hs-CRP levels in the unadjusted ITT analysis became nonsignificant in the per-protocol analysis (p = .06). A 12-week supplementation with long-chain ITFs had favourable effects on inflammatory status among PCOS patients.

Cardiovascular Health Does Not Change Following High-Intensity Interval Training in Women with Polycystic Ovary Syndrome.

Introduction: polycystic ovary syndrome (PCOS) is associated with cardiovascular disease (CVD) risk factors. First-line therapy for PCOS is lifestyle changes including exercise. We compared CVD risk factors between women with and without PCOS and examined the responses to high-intensity interval training (HIIT). Methods: women with PCOS were randomized to HIIT (n = 41) or a non-exercise control group (n = 23) for 16 weeks. Women without PCOS (n = 15) were age- and BMI-matched to participants with PCOS and completed 16 weeks of HIIT. CVD markers included blood pressure, heart rate, flow mediated dilatation (FMD), carotid intima-media thickness (IMT), and circulating concentrations of lipids, glucose, insulin, and matrix metalloproteinase-9 (MMP-9). Results: resting heart rate was higher in women with PCOS than without PCOS (p =0.011) and was reduced after HIIT in women with PCOS (−2.8 beats/min, 95% CI: −5.4, −0.2, p = 0.037). FMD was not significantly different between women with PCOS (5.5%, SD 4.1) and those without PCOS (8.2%, SD 3.9) at baseline. HIIT reduced time-to-peak dilatation of the brachial artery in women with PCOS compared with women without PCOS (−55 s, 95% CI: −96, −13, p = 0.012). Conclusions: we found little difference in CVD risk factors between women with and without PCOS at baseline, but some indications of endothelial dysfunction in women with PCOS.

Activin A causes endothelial dysfunction of mouse aorta and human aortic cells.

Preeclampsia is a multisystem hypertensive disorder of pregnancy that remains one of the leading causes of maternal and perinatal morbidity and mortality worldwide. The widespread maternal endothelial dysfunction that underlies preeclampsia is thought to arise from excessive placental production of various factors combined with enhanced oxidative stress. While previous studies have reported elevated activin A in women diagnosed with preeclampsia, whether activin A can cause vascular dysfunction has not yet been thoroughly investigated. Here, we demonstrated that different subtypes of activin A receptors were localised to the endothelial and smooth muscle cells of mouse and human aortae. Then, the aorta of healthy female C57Bl6J mice (n = 8) were incubated for 24 h in various concentrations of recombinant activin A to mimic early pregnancy (5 ng/mL), late pregnancy (20 ng/mL) and preeclampsia (50 ng/mL). Vascular reactivity as assessed by wire myography revealed that only the preeclamptic level of activin A impaired agonist-mediated endothelium-dependent relaxation by reducing the vasodilator prostanoid contribution to relaxation. However, agonist-mediated endothelium-independent mechanisms were unaffected. Further investigations carried out on human aortic endothelial cells suggested that the impairment of aorta relaxation could also be driven by increased endothelial cell permeability, and decreased cell viability, adherence and proliferation. This is the first direct evidence to show that activin A can induce endothelial dysfunction in whole blood vessels, suggesting that at high circulating levels it may contribute to the widespread endothelial dysfunction in women with preeclampsia.

Microvascular Endothelial Dysfunction in Women Living with HIV Represents Premature Aging

Microvascular Endothelial Dysfunction in Women Living with HIV Represents Premature Aging

Anxiety Disorders Are Associated With Coronary Endothelial Dysfunction in Women With Chest Pain and Nonobstructive Coronary Artery Disease.

BackgroundAnxiety disorders are the most prevalent mental disorders and are an emerging risk factor for coronary artery disease and its complications. We determine the relationship between having a clinical diagnosis of an anxiety disorder and coronary endothelial dysfunction (CED) using invasive coronary reactivity testing across both sexes.Methods and ResultsPatients presenting with chest pain and nonobstructive coronary artery disease (stenosis <40%) at coronary angiography underwent an invasive assessment of CED. Patients were categorized as having a clinical diagnosis of an anxiety disorder at the time of coronary angiography by chart review. The frequency of CED was compared between patients with versus without an anxiety disorder and after stratifying patients by sex. Between 1992 and 2020, 1974 patients (mean age, 51.3 years; 66.2% women) underwent invasive coronary reactivity testing, of which 550 (27.9%) had a documented anxiety disorder at the time of angiography. There was a significantly higher proportion of patients with any type of CED in those with an anxiety disorder in all patients (343 [62.7%] versus 790 [56.4%]; P=0.011) that persisted in women but not in men. After adjusting for covariables, anxiety was significantly associated with any CED among all patients (odds ratio [95% CI], 1.36 [1.10–1.68]; P=0.004), and after stratifying by sex in women but not in men.ConclusionsAnxiety disorders are significantly associated with CED in women presenting with chest pain and nonobstructive coronary artery disease. Thus, CED may represent a mechanism underpinning the association between anxiety disorders and coronary artery disease and its complications, highlighting the role of anxiety as a potential therapeutic target to prevent cardiovascular events.

Endothelial Dysfunction, its Relationship with Chronic Periodontal Disease, and other Associated Risk Factors

Background: Chronic periodontitis is related to individual characteristics. However, it is precisely infectious in nature with the possibility of generating a chronic systemic inflammatory response that could favour its association with diseases, such as endothelial dysfunction, hypertension, CVD, and diabetes. Purpose: The aim of the study was to analyze the relationship of endothelial dysfunction measured by flow-mediated vasodilation in the brachial artery with periodontal disease and other possible factors. Methods: A case-control study was carried out in which those who had periodontitis were defined as cases, and those who were periodontally healthy or had gingivitis were defined as controls. A clinical history was obtained from all patients, and all patients underwent biofilm control and periodontal examinations. Blood tests were performed to determine CBC, glycaemia, total cholesterol, HDL-C, and LDL-C levels, and standardized procedures were used to measure flow-mediated dilation. Results: A total of 202 patients were included in this study: 101 controls [healthy/gingivitis] and 101 cases [periodontitis]. Regarding sex, glycaemia [p = 0.019] and triglycerides [p = 0.001] levels and initial flow-mediated vasodilation [p = 0.001] and final flow-mediated vasodilation [p = 0.001] values were higher in men, while HDL values ​​were lower [p = 0.001. The average age was higher for those in the group that presented dysfunction than for those in the group without dysfunction [p = 0.014]. When analyzing the percentage of patients with endothelial dysfunction in each of the groups, there were very few positive results obtained [5 per group]. Conclusion: Initial and final arterial vasodilation was lower in women than in men. Likewise, there were more cases of endothelial dysfunction in women. In this study, patients with endothelial dysfunction were older. Periodontitis was not associated with endothelial dysfunction.

Особенности хориоретинальной гемодинамики на фоне коррекции эндотелиальной дисфункции у женщин после перенесенной преэклампсии

Purpose. To assess the clinical efficacy of drug correction of endothelial dysfunction in women at risk using the study of chorioretinal hemodynamic parameters. Material and methods. Using the prediction algorithm developed by us, 60 women were selected at risk of developing vascular retinal pathology. All women were divided into two subgroups. 1st group – 30 patients who underwent courses of drug correction of endothelial dysfunction; 2nd group included 30 women who did not receive courses of prophylactic treatment. The control group was represented by 30 women who underwent physiological pregnancy. The entire population of women underwent a study of the parameters of chorioretinal hemodynamics. Results. By the end of the follow-up period (3–4.5 years) in the 1st group there was a statistically significant improvement in the parameters of chorioretinal hemodynamics in comparison with both the 2nd group in the period 3 years after childbirth, and with the indicators of the 1st group after 6–8 months after childbirth. Conclusion. It can be argued that in the group of women who underwent long-term drug correction of endothelial dysfunction, there was a statistically significant improvement in a number of indicators of chorioretinal hemodynamics compared with women who did not receive prophylactic treatment (p&lt;0.01). Key words: chorioretinal hemodynamics, macular blood flow, linear blood flow velocity, preeclampsia, endothelial dysfunction, drug correction of endothelial dysfunction.

Endothelial dysfunction of women before and after correction of body composition

The article is devoted to the peculiarities of endothelial dysfunction of women with different types of obesity before and after correction of body composition. The article is devoted to the peculiarities of endothelial dysfunction in women with different types of obesity before and after correction of body composition. Obesity as a polygenic disease is a progressive problem of society. Numerous studies of recent decades have been devoted to the influence of excessive weight on human health, which indicate that obesity is an independent risk factor for cardiovascular disease, characterized by high mortality. The degree of cardiovascular risk in obesity depends on the distribution of adipose tissue, and hence on the normal functioning of the endothelium, since endothelial dysfunction is one of the first triggers of cardiovascular disease. The author noted that endothelial function is the most important component of homeostasis, it allows controlling the state of the vascular bed and providing blood supply to the organs both under physiological conditions and under the influence of pathologic factors. Scientific studies have shown the need of studying the functions of the endothelium in different categories of patients, women in particular. Endothelial dysfunction has been identified as an early marker of the development and progression of cardiovascular disease and beside that, obesity as a chronic inflammatory condition also provokes dysregulation of vascular homeostasis and leads to impaired vasodilatory function of the endothelium. It has been found that the degree of cardiovascular risk in obesity depends on the distribution of adipose tissue, and therefore on the normal functioning of the endothelium. The dysfunction of endothelium is one of the first steps in the development of cardiovascular disease. The necessity of amplification a body composition program for women with different degrees of obesity has been proved. An analysis of endothelial function before and after the program of correction of body composition was done. The results of analysis proved that dosed exercise and a transition to a healthy diet have been shown an improvement of the endothelial function and the reduction of both total adipose tissue and visceral fat. Keywords: endothelial dysfunction, obesity, body fat composition, physical training, healthy diet.

Endothelial function is preserved in light to moderate alcohol drinkers but is impaired in heavy drinkers in women: Flow-mediated Dilation Japan (FMD-J) study.

Light to moderate alcohol consumption has protective effects on all-cause death and coronary artery disease in women. It is thought that light to moderate alcohol consumption has a beneficial effect on vascular function in women. We measured flow-mediated vasodilation (FMD) in 702 women aged 17–86 years who provided information on alcohol consumption. We divided the subjects into four groups: non-drinkers (0 g/week), light drinkers (>0 to 140 g/week), moderate drinkers (>140 to 280 g/week) and heavy drinkers (>280 g/week). There was no significant difference in FMD among the four groups. Multivariate regression analysis revealed that alcohol consumption in non-drinkers and light drinkers was not an independent predictor of FMD (β = −0.001, P = 0.98). We compared 50 moderate drinkers and 50 non-drinkers matched for age and medical histories and 22 heavy drinkers and 22 non-drinkers in matched pair analysis. There was no significant difference in FMD between moderate drinkers and non-drinkers (8.2±4.3% vs. 8.1±3.5, P = 0.91), while FMD in heavy drinkers was significantly lower than that in non-drinkers (5.9±2.5% vs. 8.9±3.5%, P = 0.002). These findings suggest that heavy alcohol consumption is associated with endothelial dysfunction but that light to moderate alcohol consumption is not associated with endothelial dysfunction in women.Clinical trial registration information This study was approved by principal authorities and ethical issues in Japan (University Hospital Medical Information Network UMIN000012952, 01/12/2009). www.umin.ac.jp/.