Changes In Vascular Function Research Articles

Protective Effect of Coriander (Coriandrum sativum L.) on High-Fructose and High-Salt Diet-Induced Hypertension: Relevant to Improvement of Renal and Intestinal Function.

Hypertension has become a leading cardiovascular risk factor worldwide. In this study, we explored the salutary effects and relevant mechanisms of coriander (Coriandrum sativum L.), an herbal plant with culinary and medicinal values, on high-fructose and high-salt diet (HFSD)-induced hypertension in SD rats. Our results showed that oral administration of coriander (1.0 or 2.0 g/kg·bw) effectively attenuated HFSD-induced elevation of systolic blood pressure, diastolic blood pressure, and mean arterial pressure. Coriander also increased the serum levels of vasodilator factors (PGI2, NO, and eNOS), decreased Na+ retention and serum uric acid (UA) level, and ameliorated glucolipid profiles. qPCR results revealed that coriander downregulated the mRNA expression of NHE3, a Na+/H+ exchanger responsible for Na+ absorption, in kidney and small intestine. 16S rDNA sequencing showed that coriander altered the gut microbiota composition with the beneficial bacteria Bifidobacterium and Oscillibacter significantly enriched. Correlation analysis indicated that the abundance of Bifidobacterium was evidently correlated with levels of NHE3, NO, eNOS, and UA. LC-MS/MS analysis revealed that coriander contained a variety of flavonoids including rutin and quercetin. Conclusively, long-term consumption of coriander may ameliorate HFSD-induced hypertension by mitigating HFSD-caused abnormal changes in vascular endothelial function, renal and intestinal sodium absorption, glucolipid homeostasis, and gut microbiota in rats.

Pathological changes within the cerebral vasculature in Alzheimer's disease: New perspectives.

Cerebrovascular disease underpins vascular dementia (VaD), but structural and functional changes to the cerebral vasculature contribute to disease pathology and cognitive decline in Alzheimer's disease (AD). In this review, we discuss the contribution of cerebral amyloid angiopathy and non-amyloid small vessel disease in AD, and the accompanying changes to the density, maintenance and remodelling of vessels (including alterations to the composition and function of the cerebrovascular basement membrane). We consider how abnormalities of the constituent cells of the neurovascular unit - particularly of endothelial cells and pericytes - and impairment of the blood-brain barrier (BBB) impact on the pathogenesis of AD. We also discuss how changes to the cerebral vasculature are likely to impair Aβ clearance - both intra-periarteriolar drainage (IPAD) and transport of Aβ peptides across the BBB, and how impaired neurovascular coupling and reduced blood flow in relation to metabolic demand increase amyloidogenic processing of APP and the production of Aβ. We review the vasoactive properties of Aβ peptides themselves, and the probable bi-directional relationship between vascular dysfunction and Aβ accumulation in AD. Lastly, we discuss recent methodological advances in transcriptomics and imaging that have provided novel insights into vascular changes in AD, and recent advances in assessment of the retina that allow in vivo detection of vascular changes in the early stages of AD.

Quantification of Vascular Parameters in Whole Mount Retinas of Mice with Non-Proliferative and Proliferative Retinopathies.

Retinopathies are a heterogeneous group of diseases that affect the neurosensory tissue of the eye. They are characterized by neurodegeneration, gliosisand a progressive change in vascular function and structure. Although the onset of the retinopathies is characterized by subtle disturbances in visual perception, the modifications in the vascular plexus are the first signs detected by clinicians. The absence or presence of neovascularization determines whether the retinopathy is classified as either non-proliferative (NPDR) or proliferative (PDR). In this sense, several animal models tried to mimic specific vascular features of each stage to determine the underlying mechanisms involved in endothelium alterations, neuronal death and other events taking place in the retina. In this article, we will provide a complete description of the procedures required for the measurement of retinal vascular parameters in adults and early birth mice at postnatal day (P)17. We will detail the protocols to carry out retinal vascular staining with Isolectin GSA-IB4 in whole mounts for later microscopic visualization. Key steps for image processing with Image J Fiji software are also provided, therefore, the readers will be able to measure vessel density, diameter and tortuosity, vascular branching, as well as avascular and neovascular areas. These tools are highly helpful to evaluate and quantify vascular alterations in both non-proliferative and proliferative retinopathies.

Glucose Metabolic Disorders Enhance Vascular Dysfunction Triggered by Particulate Air Pollution: a Panel Study.

Vascular dysfunction is a biological pathway whereby particulate matter (PM) exerts deleterious cardiovascular effects. The effects of ambient PM on vascular function in prediabetic individuals are unclear. A panel study recruited 112 Beijing residents with and without prediabetes. Multiple vascular function indices were measured up to 7 times. The associations between vascular function indices and short-term exposure to ambient PM, including fine particulate matter (PM2.5), ultrafine particles, accumulation mode particles, and black carbon, and the modification of these associations by glucose metabolic status were examined using linear mixed-effects models. Increases in brachial artery pulse pressure, central aortic pulse pressure, and ejection duration, and decreases in subendocardial viability ratio and reactive hyperemia index were significantly associated with at least one PM pollutant in all participants, indicating increased vascular dysfunction. For example, for an interquartile range increment in 5-day moving average ultrafine particles, brachial artery pulse pressure, and central aortic pulse pressure increased 5.4% (0.8%-10.4%) and 6.2% (1.2%-11.5%), respectively. Additionally, PM-associated changes in vascular function differed according to glucose metabolic status. Among participants with high fasting blood glucose levels (≥6.1 mmol/L), PM exposure was significantly associated with increased brachial artery systolic blood pressure, central aortic systolic blood pressure, brachial artery pulse pressure, central aortic pulse pressure, and augmentation pressure normalized to a heart rate of 75 bpm and decreased subendocardial viability ratio and reactive hyperemia index. Weaker or null associations were observed in the low-fasting blood glucose group. Glucose metabolic disorders may exacerbate vascular dysfunction associated with short-term ambient PM exposure.

Phenylephrine-Induced Cardiovascular Changes in the Anesthetized Mouse: An Integrated Assessment of in vivo Hemodynamics Under Conditions of Controlled Heart Rate.

ObjectiveInvestigating the cardiovascular system is challenging due to its complex regulation by humoral and neuronal factors. Despite this complexity, many existing research methods are limited to the assessment of a few parameters leading to an incomplete characterization of cardiovascular function. Thus, we aim to establish a murine in vivo model for integrated assessment of the cardiovascular system under conditions of controlled heart rate. Utilizing this model, we assessed blood pressure, cardiac output, stroke volume, total peripheral resistance, and electrocardiogram (ECG).HypothesisWe hypothesize that (i) our in vivo model can be utilized to investigate cardiac and vascular responses to pharmacological intervention with the α1-agonist phenylephrine, and (ii) we can study cardiovascular function during artificial pacing of the heart, modulating cardiac function without a direct vascular effect.MethodsWe included 12 mice that were randomly assigned to either vehicle or phenylephrine intervention through intraperitoneal administration. Mice were anesthetized with isoflurane and intubated endotracheally for mechanical ventilation. We measured blood pressure via a solid-state catheter in the aortic arch, blood flow via a probe on the ascending aorta, and ECG from needle electrodes on the extremities. Right atrium was electrically paced at a frequency ranging from 10 to 11.3 Hz before and after either vehicle or phenylephrine administration.ResultsPhenylephrine significantly increased blood pressure, stroke volume, and total peripheral resistance compared to the vehicle group. Moreover, heart rate was significantly decreased following phenylephrine administration. Pacing significantly decreased stroke volume and cardiac output both prior to and after drug administration. However, phenylephrine-induced changes in blood pressure and total peripheral resistance were maintained with increasing pacing frequencies compared to the vehicle group. Total peripheral resistance was not significantly altered with increasing pacing frequencies suggesting that the effect of phenylephrine is primarily of vascular origin.ConclusionIn conclusion, this in vivo murine model is capable of distinguishing between changes in peripheral vascular and cardiac functions. This study underlines the primary effect of phenylephrine on vascular function with secondary changes to cardiac function. Hence, this in vivo model is useful for the integrated assessment of the cardiovascular system.

Gradual Not Sudden Change: Multiple Sites of Functional Transition Across the Microvascular Bed.

In understanding the role of the neurovascular unit as both a biomarker and target for disease interventions, it is vital to appreciate how the function of different components of this unit change along the vascular tree. The cells of the neurovascular unit together perform an array of vital functions, protecting the brain from circulating toxins and infection, while providing nutrients and clearing away waste products. To do so, the brain’s microvasculature dilates to direct energy substrates to active neurons, regulates access to circulating immune cells, and promotes angiogenesis in response to decreased blood supply, as well as pulsating to help clear waste products and maintain the oxygen supply. Different parts of the cerebrovascular tree contribute differently to various aspects of these functions, and previously, it has been assumed that there are discrete types of vessel along the vascular network that mediate different functions. Another option, however, is that the multiple transitions in function that occur across the vascular network do so at many locations, such that vascular function changes gradually, rather than in sharp steps between clearly distinct vessel types. Here, by reference to new data as well as by reviewing historical and recent literature, we argue that this latter scenario is likely the case and that vascular function gradually changes across the network without clear transition points between arteriole, precapillary arteriole and capillary. This is because classically localized functions are in fact performed by wide swathes of the vasculature, and different functional markers start and stop being expressed at different points along the vascular tree. Furthermore, vascular branch points show alterations in their mural cell morphology that suggest functional specializations irrespective of their position within the network. Together this work emphasizes the need for studies to consider where transitions of different functions occur, and the importance of defining these locations, in order to better understand the vascular network and how to target it to treat disease.

ITRAQ-based identification of differentially expressed proteins in ED rat model induced by cold stress combined with environmental oestrogen.

We aim to identify serum biomarkers and key proteins of erectile dysfunction (ED) induced by cold stress combined with environmental oestrogen through iTRAQ combined with LC-MS/MS. ED rat model was established by using oestrogen-like feed and cold stimulation. Differentially expressed proteins in serum were screened and analysed with iTRAQ combined with LC-MS/MS and IPA bioanalysis platform. We found that 35 proteins were differentially expressed in the ED group, including 31 upregulated and four downregulated proteins. The molecular functions of differential proteins mainly involved the activation of endopeptidase inhibitor and regulator. The main pathways involved were the FXR/RXR activation signalling pathway and the acute phase response signalling pathway. Furthermore, three protein markers related to ED were obtained, namely C-reactive protein (CRP), T-kininogen 1 and apolipoprotein Protein H (APOH). ELISA results showed that compared with the control group, proteins of HPX, TTR, APOH, RBP4, CRP and ORM1 were significantly upregulated, but ANGPT1 protein was significantly downregulated in the serum of the ED group (p<0.05). Conclusively, the candidate serum markers for ED induced by cold stress combined with environmental hormones were obtained. Our results indicate that inflammation and vascular endothelial function changes may play a key role in the occurrence and development of ED.

Changes in glycemic variability, gastric emptying and vascular endothelial function after switching from twice-daily to once-weekly exenatide in patients with type 2 diabetes: a subpopulation analysis of the twin-exenatide study

BackgroundWe investigated the changes in blood glucose fluctuation, gastric emptying, and vascular endothelial function by switching from an exenatide twice-daily formulation (BID) to a once-weekly formulation (QW) since the evaluation of postprandial glucose excursion and glycemic variability (GV) by continuous glucose monitoring (CGM) after switching was lacking.MethodsTwenty-nine patients with type 2 diabetes treated with exenatide BID were included in this study and switched to exenatide QW for 24 weeks. GV assessed by CGM, gastric emptying (by 13 C-acetate breath test) and vascular endothelial function (by reactive hyperemia - peripheral arterial tonometry) were evaluated at baseline and 24 weeks after switching.ResultsHbA1c decreased significantly from the baseline to week 24, while postprandial glucose levels after breakfast and dinner significantly increased (both P <0.05). However, the increases in GV indices were modest and not statistically significant at week 24. Vascular endothelial function was also not significantly changed after switching (P >0.05). Gastric emptying was significantly accelerated at week 24 (Tmax 83.4 ± 12.1 min vs. 58.2 ± 16.4 min) (P <0.001) and correlated with increased postprandial glucose levels after breakfast and dinner (both P <0.05).ConclusionsDespite the increase in postprandial glucose associated with accelerated gastric emptying after switching from exenatide BID to QW, change in GV was modest and no significant deterioration in vascular endothelial function was observed after switching. These results support the superiority of treatment with exenatide QW over exenatide BID in clinical practice; however, attention should be paid to the monitoring and management of postprandial glucose levels when selecting exenatide QW.Trial registrationClinical trial registry number; UMIN000016390 and jRCTs031180320.Approval date of Registry and the Registration: December 12, 2014.

Changes in mandibular CDH5, CXCL1, and PECAM1 expression following exposure to bisphosphonate and molar extraction suggest a loss of vascular endothelial cell barrier integrity plays a role in MRONJ

Objectives: Medication related osteonecrosis of the jaw (MRONJ) is a disorder characterized by loss of blood supply to the jaws and death to the bone. In our previous work, we created a rat model of MRONJ by multiple injections of 60ug/Kg zoledronic acid (ZA) via tail vein followed by extraction of a single first molar. We have previously shown in this model a decrease in the vasculature of the jaws and a delay in bone healing after 6 weeks. The current study was designed to look at mRNA expression and immunohistochemical localization of three endothelial cell markers (CDH5, CXCL1 and PECAM1) 6 weeks following ZA injection with and without molar extraction and in saline injected rats as controls. The objective of this study is to determine if the expression of these markers may serve to identify clinically significant changes in vascular endothelium barrier function associated with the onset of MRONJ. Methods: Using RT-PCR, we analyzed the expression of mRNA for angiogenic markers, six weeks after injection with either 60ug/Kg ZA or saline as a control and in ZA injected rats following first molar extraction. Routine immunohistochemical procedures with antibodies specific for rat marker proteins were used to study the immunohistochemical localization of proteins translated from the mRNA angiogenic markers with significant expression. All tissues were processed together under identical conditions. Results: We found a decrease in the mRNA expression of CDH5, and PECAM1 and an increase in CXCL1 expression six weeks after extraction and ZA injection in our rat model of MRONJ. Rat monoclonal antibodies specific for protein epitopes expressed by these genes (VE-cadherin, C-X-C motif ligand 1(CXCl1), and PECAM-1) were then used to localize proteins for these markers in tissues from ZA, saline-injected control rats, and MRONJ rats. The results show the absence of immunohistochemical localization of PECAM-1 and VE-cadherin marker proteins (-) in tissues from the MRONJ rats but strong (++++) in tissue from the saline-injected Control rats. The results also show the localization of the immunohistochemical staining for CXCl1 was high (++++) in the MRONJ rats after six weeks but absent (-) in the Controls. No mRNA or immunohistochemical localization for the three markers was seen in the rats treated with ZA without extraction. Conclusions: Our study identifies markers associated with a loss of vascular endothelial cell barrier integrity suggesting a role for this mechanism in MRONJ. This finding further suggests that CDH5, CXCL1 and PECAM1 may be useful as early markers for the changes seen in blood vessels after bisphosphonate exposure but before the frank onset of MRONJ.

Relationship Between Left Ventricular Ejection Fraction Variation and Systemic Vascular Resistance: A Prospective Cardiovascular Magnetic Resonance Study.

Introduction: This cardiovascular magnetic resonance (CMR) study aims to determine whether changes in systemic vascular resistance (SVR), obtained from CMR flow sequences, might explain the significant long-term changes in left ventricular (LV) ejection fraction (EF) observed in subjects with no cardiac disease history.Methods: Cohort subjects without any known cardiac disease but with high rates of hypertension and obesity, underwent CMR with phase-contrast sequences both at baseline and at a median follow-up of 5.2 years. Longitudinal changes in EF were analyzed for any concomitant changes in blood pressure and vascular function, notably the indexed SVR given by the formula: mean brachial blood pressure / cardiac output x body surface area.Results: A total of 118 subjects (53 ± 12 years, 52% women) were included, 26% had hypertension, and 52% were obese. Eighteen (15%) had significant EF variations between baseline and follow-up (7 increased EF and 11 decreased EF). Longitudinal changes in EF were inversely related to concomitant changes in mean and diastolic blood pressures (p = 0.030 and p = 0.027, respectively) and much more significantly to SVR (p < 0.001). On average, these SVR changes were −8.08 ± 9.21 and +8.14 ± 8.28 mmHg.min.m2.L−1, respectively, in subjects with significant increases and decreases in EF, and 3.32 ± 7.53 mmHg.min.m2.L−1 in subjects with a stable EF (overall p < 0.001).Conclusions: Significant EF variations are not uncommon during the long-term CMR follow-up of populations with no evident health issues except for uncomplicated hypertension and obesity. However, most of these variations are linked to SVR changes and may therefore be unrelated to any intrinsic change in LV contractility. This underscores the benefits of specifically assessing LV afterload when EF is monitored in populations at risk of vascular dysfunction.Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT01716819 and NCT02430805.

Single-Cell Analysis Identify Transcription Factor BACH1 as a Master Regulator Gene in Vascular Cells During Aging.

Vascular aging is a potent driver of cardiovascular and cerebrovascular diseases. Vascular aging features cellular and functional changes, while its molecular mechanisms and the cell heterogeneity are poorly understood. This study aims to 1) explore the cellular and molecular properties of aged cardiac vasculature in monkey and mouse and 2) demonstrate the role of transcription factor BACH1 in the regulation of endothelial cell (EC) senescence and its mechanisms. Here we analyzed published single-cell RNA sequencing (scRNA-seq) data from monkey coronary arteries and aortic arches and mouse hearts. We revealed that the gene expression of YAP1, insulin receptor, and VEGF receptor 2 was downregulated in both aged ECs of coronary arteries’ of monkey and aged cardiac capillary ECs of mouse, and proliferation-related cardiac capillary ECs were significantly decreased in aged mouse. Increased interaction of ECs and immunocytes was observed in aged vasculature of both monkey and mouse. Gene regulatory network analysis identified BACH1 as a master regulator of aging-related genes in both coronary and aorta ECs of monkey and cardiac ECs of mouse. The expression of BACH1 was upregulated in aged cardiac ECs and aortas of mouse. BACH1 aggravated endothelial cell senescence under oxidative stress. Mechanistically, BACH1 occupied at regions of open chromatin and bound to CDKN1A (encoding for P21) gene enhancers, activating its transcription in senescent human umbilical vein endothelial cells (HUVECs). Thus, these findings demonstrate that BACH1 plays an important role in endothelial cell senescence and vascular aging.

Methylation-reprogrammed CHRM3 results in vascular dysfunction in the human umbilical vein following IVF-ET†.

Assisted reproductive technology (ART) has been used globally among infertile couples. However, many epidemiological investigations have indicated that ART is associated with a range of long-term adverse health outcomes in offspring, including cardiovascular disease, obesity, and increased plasma lipid levels. Until now, direct evidence has been limited regarding the pathological changes in vascular function in fetuses with ART. In this study, human umbilical cords were collected from healthy normal pregnancies and in vitro fertilization and embryo transfer (IVF-ET) pregnancies. Vascular functional studies involving acetylcholine (ACh), antagonists of its specific receptors, and L-type calcium channel/PKC-MLC20 phosphorylation pathway specific inhibitors were conducted. Quantitative real-time PCR, Western blotting, and methylation analyses were performed on umbilical vein samples. We found that the umbilical vein constriction induced by ACh in the IVF-ET group was significantly attenuated compared with that in the healthy normal pregnancy group, which was not only associated with the hypermethylation of ACh muscarinic receptor subtype 3 (CHRM3) and decreased expression of CHRM3, PKCβ, and CaV1.2, but was also related to the reduced phosphorylation of MLC20. This study revealed that the hypermethylation of CHRM3, leading to a reduction in CHRM3 expression and downregulation of the CaV1.2/PKC-MLC20 phosphorylation pathway, was responsible for the decreased sensitivity to ACh observed in the umbilical vein under IVF-ET conditions. The hypermethylation of CHRM3 caused by IVF-ET might play an important role in altered vasoconstriction and impact cardiovascular systems in the long run.

Some features of the influence of nitrogen oxide on humans at rest, physical activity and pathology

The literature data on the general characteristics and mechanisms of action of nitric oxide, its role in the regulation of the functioning of the cardiovascular system and the body as a whole are used in the work. The existing NO-dependent mechanism of regulation of vascular reactivity in the conditions of endothelial dysfunction is stated; cGMP-independent mechanism of NO action on calcium homeostasis and sensitivity of smooth muscle myofibrils to calcium ions. Interesting are the results of studies that reflect the importance of nitric oxide in health. Age-related changes in vascular endothelial function due to increasing age and their importance in the development of age-related pathology are shown. Materials that reflect the importance of the use of nitric oxide donors for the treatment of diseases of various body systems, as well as factors of pharmacological correction of disorders of NO metabolism and associated with these changes endothelial dysfunction. Much attention is paid to the work, which reflects the role of nitric oxide in improving physical performance and the importance of this effect in the lives of athletes. The effect of nitric oxide on microorganisms, the use of nitric oxide in the treatment of infectious diseases, in particular during viral infection, is proved. The contribution of Ukrainian scientists in studying the effects of nitric oxide on the body of healthy and sick people, the elderly and senile, as well as the role in the creation of pharmacological drugs, nitric oxide donors for the prevention and treatment of diseases.

Comparison of high intensity interval training with standard cardiac rehabilitation on vascular function.

To compare the short- and long-term effects of high-intensity interval training (HIIT) with usual care moderate intensity continuous training (MICT) on systemic vascular function and stiffness in patients with coronary artery disease undergoing a cardiac rehabilitation program. Randomized controlled trial. Fifty-four patients (age=63±8years, 93% male) were randomized to complete 3sessions/week (2supervised, 1home-based) of either (1) 4×4-min HIIT or (2) 40-min MICT, for 4weeks. Patients then continued 3 unsupervised home-based sessions/week of their allocated training for 11months. Brachial artery flow-mediated dilation, pulse wave velocity, and blood pressure were measured at baseline, 4weeks, 3months, 6months, and 12months. Data were analyzed using linear mixed modeling and are presented as mean change from baseline (95% CI). HIIT showed a greater improvement in flow-mediated dilation compared to MICT after 4weeks [1.5% (0.9, 2.1) vs 0.1% (-0.5, 0.8); p=0.004) but not 12months [1.2% (-0.2, 2.5) vs 0.4% (-0.8, 1.7); p=0.153). There were no short- or long-term group differences for changes in pulse wave velocity, peripheral or central blood pressure between HIIT and MICT after 4weeks, or over 12months. A 4-week HIIT program was superior to MICT for improving vascular function, but not arterial stiffness or blood pressure. Over 12months, changes in vascular function, blood pressure, and arterial stiffness were similar for HIIT and MICT.

Egg consumption improves vascular and gut microbiota function without increasing inflammatory, metabolic, and oxidative stress markers.

Egg consumption is one of the many inconsistencies in evidence linking dietary cholesterol to cardiovascular disease (CVD). In addition, the gut microbiota and its metabolite, trimethylamine‐N‐oxide (TMAO), have been shown to play a crucial role in the development of CVD. The fact that egg is rich in choline suggests that excessive egg consumption may increase TMAO production by altering the gut microbiota. However, the effects of egg consumption on vascular function and gut microbiota remain unclear. Here, the diet of nine young male subjects was supplemented with two boiled eggs daily for 2 weeks. Changes in vascular function, inflammation, metabolism, oxidative stress, and gut microbiota were examined. We found that egg consumption increased flow‐mediated dilation and decreased brachial‐ankle pulse wave velocity. Furthermore, egg consumption positively modulated the gut microbiota function but had no effects on the levels of C‐reactive protein, glucose, lipid profile, malondialdehyde, superoxide dismutase, or TMAO. The current study provides evidence that egg consumption improves vascular function, which may be related to the alterations seen in the gut microbiota. Therefore, moderate egg consumption may help to improve vascular and intestinal function in individuals at low risk of developing CVD and other metabolic disorders.

Chronic Kidney Disease and Arterial Stiffness: A Two-Way Path.

The kidney-heart relationship has raised interest for the medical population since its vast and complex interaction significantly impacts health. Chronic kidney disease (CKD) generates vascular structure and function changes, with significant hemodynamic effects. The early arterial stiffening in CKD patients is a consequence of the interaction between oxidative stress and chronic vascular inflammation, leading to an accelerated deterioration of left ventricular function and alteration in tissue perfusion. CKD amplifies the inflammatory cascade's activation and is responsible for altering the endothelium function, increasing the vascular tone, wall thickening, and favors calcium deposits in the arterial wall. Simultaneously, the autonomic imbalance, and alteration in other hormonal systems, also favor the overactivation of inflammatory and fibrotic mediators. Thus, hormonal disarrangement also contributes to structural and functional lesions throughout the arterial wall. On the other hand, a rise in arterial stiffening and volume overload generates high left ventricular afterload. It increases the left ventricular burden with consequent myocardial remodeling, development of left ventricular hypertrophy and, in turn, heart failure. It is noteworthy that reduction in glomerular mass of renal diseases generates a compensatory glomerular filtration overdriven associated with large-arteries stiffness and high cardiovascular events. Furthermore, we consider that the consequent alterations of the arterial system's mechanical properties are crucial for altering tissue perfusion, mainly in low resistance. Thus, increasing the knowledge of these processes may help the reader to integrate them from a pathophysiological perspective, providing a comprehensive idea of this two-way path between arterial stiffness and renal dysfunction and their impact at the cardiovascular level.

Effect of Tirofiban Injection on vascular endothelial function, cardiac function and inflammatory cytokines in patients with acute myocardial infarction after emergency Percutaneous Coronary Intervention.

ABSTRACTObjectives:To evaluate the effect of tirofiban injection on vascular endothelial function, cardiac function, inflammatory cytokines and other indicators in patients with acute myocardial infarction after emergency PCI and its clinical significance.Methods:Eighty patients with acute myocardial infarction admitted to Affiliated Hospital of Hebei University from March 18, 2020 to October 18, 2020 were enrolled and randomly divided into two groups: the experimental group and the control group, with 40 cases in each group. Patients in both groups underwent PCI. Patients in the control group were given oxygen inhalation, monitoring, and basic medications for myocardial infarction, such as nutritional myocardial drugs, statins, aspirin, nitrates, clopidogrel, and β-blockers. In contrast, patients in the experimental group received tirofiban 10 ug/kg intravenously over 5min immediately before PCI in addition to basic treatment, and then tirofiban 0.1 ug/(kg/min) was pumped via intravenous pump postoperatively for 48 hour. The changes of vascular endothelial function, cardiac function and adverse drug reactions (ADRs) in the two groups before treatment, one week and one month after treatment, as well as changes of inflammatory cytokines such as CRP and IL-6 in the two groups before and after treatment were compared and analyzed.Results:Compared with the control group, FMD, NO, ET-1 and other indexes in the experimental group were significantly improved one week and one month after treatment, with statistically significant differences (p<0.05). BNP, LVEDD, LVEF and additional indexes in the experimental group were significantly lower than those in the control group at one week and one month after treatment, with statistically significant differences (p=0.00). Moreover, the incidence of ST-segment fallback > 70% in the experimental group was 72.5% after treatment, which was significantly better than that of 47.5% in the control group, with a statistically significant difference (p=0.03). CRP and IL-6 in the experimental group were significantly lower than those in the control group after treatment, with a statistically significant difference (p=0.00). There was no statistical significance in the incidence of ADRs between the two groups after treatment (p=0.42).Conclusion:Tirofiban injection after emergency PCI is a beneficial treatment regime for patients with STEMI. With such a treatment regime, cardiac function and vascular endothelial function of patients can be dramatically improved, coronary blood supply will be ameliorated, inflammatory cytokines can be reduced, and no significant increase can be seen in the incidence of adverse reactions.

Abstract 13111: Circulating Extracellular Microvesicles: Mediators of Altitude-Related Vascular Inflammation

Ascent to high altitude can adversely affect cardio- and cerebrovascular health, particularly in those with pre-existing disease. Pathologic vascular responses to acute and subacute high altitude exposure include, endothelial dysfunction, cerebral and pulmonary edema as well as pulmonary hypertension. Changes in vascular endothelial cell function, most notably the induction of a proinflammatory endothelial phenotype, is thought to be an underlying factor. Endothelial inflammation can induce cerebral edema in stroke and promote pulmonary edema. The mechanisms underlying high-altitude related vascular inflammation remain unclear. The vascular endothelium is significantly influenced by circulating cell-derived microvesicles (MVs). MVs are small (100-1000 nm) membrane vesicles that are released by various cell types (e.g. endothelial, platelets, leukocytes) in response to a myriad of physiologic and pathologic stimuli including hypoxia. Circulating MVs have emerged as biomarkers and mediators of endothelial inflammation. We tested the hypothesis that ascent to high altitude induces a proinflammatory circulating MV phenotype. Ten healthy adults (8 M/2 F; age: 28 + 2 yr ) residing at sea level (Kelowna, BC, Canada) were studied prior to and 4-6 days after ascending to high altitude (Cerro de Pasco, Peru; 4300 m). Circulating MVs were isolated, enumerated and collected from plasma by flow cytometry. Human umbilical vein endothelial cells were cultured and treated with MVs collected from each subject at sea level and altitude. Circulating MVs were significantly higher at altitude vs sea level (26637 + 3315 vs19388 + 1699 MV/μL). Altitude-related MVs induced higher (~25%; P&lt;0.05) release of interleukin (IL)-6 (63.9±3.9 vs 53.3±3.6 pg/mL) and IL-8 (140.2±3.6 vs 120.7±3.8 pg/mL) compared with MVs harvested at sea level. Although intracellular expression of total NF-κB p65 (83.4 + 6.7 vs 90.2 + 6.9 AU) was not significantly affected, high altitude-MVs resulted in ~55% higher (P&lt;0.05) cell expression of p-NF-κB p65 (active NF-κB: 129.6 + 19.8 vs 90.7 + 10.5 AU) than sea level-MVs. Circulating extracellular MVs increase at high altitude and induce endothelial inflammation, potentially contributing to altitude-related vascular pathologies.

Abstract 12986: Association of Gestational Diabetes With Subclinical Cardiovascular Disease on Echocardiogram and Endothelial Function Testing

Introduction: Gestational diabetes mellitus (GDM) increases risk for cardiovascular disease (CVD). The subclinical cardiovascular structural and functional changes that contribute to long-term cardiovascular risk are unclear. Hypothesis: We hypothesized that GDM is associated with adverse cardiovascular remodeling, diastolic function abnormalities, and endothelial dysfunction at approximately a decade after delivery, thereby increasing CVD risk. Methods: We conducted a cross-sectional analysis of women from an existing cohort with abstracted clinical pregnancy data. Women attended a follow-up visit at a median of 9 years after delivery. Echocardiograms, Peripheral Arterial Tonometry (EndoPAT), glycocalyx analysis (GlycoCheck) and laboratory testing were conducted at the follow-up visit. Results: Among 217 women who attended the follow-up visit, 53 (24%) had history of GDM. After adjusting for age, race, preeclampsia history or preterm delivery, women with prior Compared to women without GDM, women with prior GDM had higher interventricular septal and left ventricular (LV) posterior wall thickness and lower septal e’ velocity ( Table ; Model 2). They also had worse endothelial function with lower reactive hyperemia index (RHI) and adverse GlycoCheck parameters. Measures of hypertrophy were attenuated by additional adjustment for body mass index, hypertension, and diabetes (Model 3), but findings of adverse LV diastology, RHI and GlycoCheck parameters remained significant. Conclusions: Women with GDM were more likely to have increased LV wall thickness, adverse diastology and endothelial dysfunction nearly a decade postpartum. Adjusting for traditional cardiovascular risk factors attenuated some but not all parameters. These findings suggest that subclinical structural and functional cardiac and vascular changes may be a mechanism by which GDM causes increased risk of CVD.

Vascular dysfunction and its recovery after transradial coronary angioplasty- A serial observational study

ObjectiveTo serially evaluate the effect of trans-radial coronary angioplasty (TRA) on the vascular function of radial artery (RA) and upstream brachial artery (BA) and to find out the relative contribution of endothelial dependent flow-mediated vasodilatation (FMD) and endothelial independent nitrate mediated dilatation (NMD). MethodsForty patients of chronic stable angina with successful TRA were studied. FMD and NMD of bilateral RA and BA were measured with high-resolution ultrasound, before and at 24 h and at 3 months, after catheterization. ResultsFMD as well as NMD were significantly decreased in right RA (16.3 ± 3.6% to 5.7 ± 1.8%; p = 0.001, and 24.1 ± 5.3% to 9.7 ± 2.8%; p = 0.001, respectively) as well as in upstream BA (17.0 ± 1.6% to 9.4 ± 0.5%; p = 0.001,and 26.5 ± 6.8% to 20.5 ± 3.7%; p = 0.001, respectively) at 24 h. FMD/NMD ratio was also decreased in RA (70 ± 10% to 60 ± 10%; p = 0.04) and as well as in BA (70 ± 20% to 50 ± 10%; p = 0.03). The endothelial dysfunctions returned to normal at 3 months. Control arm did not show any change in vascular function at any point of time. Radial artery diameter/sheath ratio <1 and catheter exchanges >2 were the independent predictors for >50% decrease in FMD. ConclusionsTRA results in reversible depression in FMD as well as NMD in the radial artery as well as upstream brachial artery. These vascular dysfunctions are limited to the catheterized arm only and return to normal after 3 months.