Structural Vascular Changes Research Articles

Pre‐eclampsia and future cardiovascular disease: role of circulating micro‐RNAs

BackgroundWomen with a history of pre‐eclampsia (PE) are at increased risk of cardiovascular events later in life. The mechanisms underlying this association are incompletely understood but likely include changes in vascular function and structure. microRNAs (miRs) may play a role in vascular health and disease; therefore, we assessed profiles of circulating miRs in women who had PE, with or without subsequent cardiovascular disease.MethodsWe performed comprehensive profiling of circulating miRs by RNA sequencing (Qiagen, Hilden, Germany) of plasma samples from two independent cohorts: a cohort of women who presented with premature acute coronary syndrome (ACS; cohort 1: n=18 with and n=17 without history of PE) and a cohort of women without overt cardiovascular disease (cohort 2: n=20 with and n=20 without history of PE). miR profiles associated with history of PE and ACS were established based on fold change ≥ ±1.5 and P < 0.05. Targetscan 7.0 was used to predict miR targets and KEGG pathway enrichment was determined with Partek Pathway and Genomics Suite.ResultsWomen in the two cohorts were on average 48 years of age and had prior pregnancy over 20 years before. A total of 183 and 107 miRs were found to be differentially expressed between cases and controls in cohorts 1 and 2, respectively. Five miRs (hsa‐miRs 3131, 346, 4305, 4670‐3p and 5698) were concordantly increased or decreased in both cohorts. There were 39 and 29 KEGG pathways significantly (FDR <0.05) enriched in cohorts 1 and 2, respectively, of which 23 pathways overlapped between the cohorts. Further analysis identified 13 KEGG pathways that were common between all comparisons of PE vs control in cohorts 1 and 2, and ACS vs non‐ACS across the cohorts, including cancer, Wnt signalling, TGF‐beta and focal adhesion pathways (Figure 1).ConclusionsBy analysing circulating miR profiles, we identified pathways that are common between women with ACS and women with history of PE. Of particular importance, pathways involved in cell growth and adhesion may provide explanations for the link between PE and future cardiovascular diseases.Support or Funding InformationFunded by grants from the Canadian Vascular Network and the British Heart Foundation (Centre of Research Excellence award RE/13/5/30177)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Short-term changes of choroidal vascular structures after phacoemulsification surgery

BackgroundTo evaluate the changes of choroidal vascular structures in patients after phacoemulsification surgery.MethodsA self-control study was conducted on 36 eyes of 36 patients who had uneventful phacoemulsification. Choroidal images were acquired preoperatively, 7 days (D7), 1 month (M1), and 3 months (M3) after surgery from enhanced depth imaging (EDI) optical coherence tomography (OCT) scans. Choroidal vascularity index (CVI) was used to assess vascular status of the choroid using image binarization by the Niblack method. The postoperative values of mean CVI were compared with baseline by paired t-test. Univariate and multiple linear regression analyses were performed to determine the associations between CVI and other factors.ResultsThe mean age of the recruited patients was 63.1 ± 6.9 years. The mean CVI at baseline was 60.1 ± 5.5%. After surgery, the CVI significantly increased to 61.7 ± 5.3% at D7, 63.6 ± 4.4% at M1 and 64.8 ± 4.0% at M3 (p = 0.035, 0.0006, < 0.0001, respectively). Univariate and multiple regression analysis revealed a positive association between CVI and subfoveal choroidal thickness (SFCT) at pre-operation and no significant association with age, axial length (AL), intraocular pressure (IOP) and gender at all timepoints.ConclusionsPhacoemulsification induced increased CVI in patients diagnosed with cataract. Evaluation of the long-term change of CVI following surgery may provide valuable information for studying the relationship between phacoemulsification and disorders of the choroid.

Abstract P362: Central Arterial Stiffness Increases Within One Year-interval of the Final Menstrual Period in Midlife Women: Study of Women's Health Across the Nation (SWAN) Heart

Introduction: Substantial hormonal and adverse lipid changes have been reported within one-year interval of the final menstrual period (FMP) suggesting this interval as a critical time period in midlife women. Significant structural vascular remodeling has been documented during the late peri-menopausal stage, a stage characterized by amenorrhea for at least 3 months. Whether vascular functional changes also accompany the menopause transition and occur within one-year interval of the FMP is not clear. Central arterial stiffness as measured by aortic pulse wave velocity (aPWV), is a marker of vascular functional changes and a significant predictor of CVD events. Our aim was to test whether the change in aPWV differs by time elapsed since the FMP in midlife women. We hypothesized that aPWV would significantly increase within one-year of the FMP independent of aging and traditional CVD risk factors. Methods: We evaluated participants with no self-reported CVD from the Study of Women’s Health Across the Nation (SWAN) Heart Ancillary study, a study of subclinical measures of atherosclerosis in midlife women at the Pittsburgh and Chicago sites. Women had up to two aPWV scans over a median of 2.2 years of follow-up and known FMP dates. Yearly % changes in aPWV were estimated in three time segments relative to the FMP (segment 1: more than 1 year before FMP, segment 2: within 1 year before and after FMP, and segment 3: more than 1 year after FMP) and compared using piecewise linear mixed-effects model with random intercepts. Final model was adjusted for time-varying age, race, study site, baseline systolic blood pressure, waist circumference, insulin resistance, physical activity, and history of hormone therapy use. Results: The study included 304 women (At baseline: age mean(SD): 51.1(2.8) y; 62% White, 38% Black; 10% premenopausal, 52% early perimenopausal, 12% late perimenopausal, and 26% postmenopausal). In final model, estimates of the annual % change (95% CI) in aPWV were: -0.6% (-2.1%, 0.8%) for more than one year before the FMP, 3.8% (0.3%, 7.4%) within one year-interval of the FMP, and -2.1% (-4.0%, -0.1%) for more than one year after the FMP. The estimated annual % change in aPWV within the one year-interval of the FMP was significantly greater than the estimated changes in the other two segments in final model, p&lt;0.05 for both comparisons. Conclusions: The one year-interval around the FMP is a critical period in women’s life when vascular functional alterations occur in central arteries independent of aging. These results are consistent with previous findings showing significant vascular structural changes and lipid levels worsening around the time of the FMP. Future research should examine the impact of the reported vascular functional changes on CVD risk after menopause.

Localized Marked Elongation of the Distal Internal Carotid Artery with or without PHACE Syndrome: Segmental Dolichoectasia of the Distal Internal Carotid Artery.

Segmental intracranial dolichoectasia of the distal ICA is a feature of PHACE syndrome or a sporadic phenomenon. We evaluated the relationship between intracranial dolichoectasia of the distal ICA and PHACE syndrome and illustrated the characteristic radiologic findings of the lesions. Intracranial dolichoectasia of the distal ICA was identified in 20 patients at our institution from 2005 to 2016 through a review of diagnostic cerebral angiography results. All radiologic images were reviewed to determine the vascular morphologic dispositions around the distal ICA, including dysplasia, mural calcification, vessel wall enhancement, lumen narrowing, and aneurysm formation. Medical records were reviewed to determine the symptoms of PHACE syndrome. Subsequently, the correlation between radiologic findings and PHACE syndrome was assessed. In this cohort, which had a strong female predominance (male/female ratio= 2:18), intracranial dolichoectasia had a more ipsilateral vascular morphologic disposition. Mural calcification was detected more frequently in elderly patients, whereas vessel wall enhancement was detected more frequently in younger patients. Follow-up images showed a slow progression of the lesions. However, no significant differences in the vascular morphologic disposition and brain structural changes were observed between patients with (n = 11) and without (n = 9) PHACE syndrome. The striking elongation and tortuosity of the distal ICA generally appeared to be a type of congenital lesion occurring early in embryogenesis as either a sporadic phenomenon or an arterial change associated with PHACE syndrome. Imaging findings revealed various mural abnormalities with a benign clinical course.

Progression of subclinical atherosclerosis in subjects with rheumatoid arthritis and the metabolic syndrome

Background and aimsRheumatoid arthritis (RA) has been associated with an increased risk of atherosclerosis. We aimed to evaluate the progression of carotid intima media thickness (cIMT) in RA patients subject to a cardiovascular treat-to-target intervention. In addition, the presence of the metabolic syndrome (MetS) on cIMT outcomes was evaluated. MethodsWe performed a cohort analysis of FRANCIS, in which RA patients ≤70 years without CVD or diabetes mellitus were randomized for either a treat-to-target intervention or usual care concerning CVD risk factors. MetS was scored at baseline. ResultsThree-year data was available in 212 well-controlled RA patients. The treat-to-target intervention resulted in a lower cIMT progression over three years compared to the usual care. However, there was no difference in cIMT at three years between groups.MetS was present in 40.1% of RA patients. Baseline cIMT was significantly higher in RA patients with MetS compared to those without (0.619 (0.112) versus 0.557 (0.104) mm; p < 0.001). After three years, cIMT progression was comparable (0.043 (0.071) versus 0.043 (0.072) mm; p = 0.96). In RA patients with MetS, the presence of plaques increased over three years from 12.9% to 23.5% (p = 0.01).The type of intervention had no effect on cIMT progression in RA patients with MetS. However, in subjects without MetS, treat-to-target resulted in a lower progression. ConclusionsRA patients with MetS showed an increased CVD risk profile based on both a higher prevalence of CVD risk factors and structural vascular changes. A treat-to-target approach of CVD risk factors reduced cIMT progression only in RA patients without MetS.

Diagnosing Internal Herniation After Roux-en-Y Gastric Bypass Surgery: Literature Overview, Cadaver Study and the Added Value of 3D CT Angiography

PurposeThe purposes of the study are to outline the complexity of diagnosing internal herniation after Roux-en-Y gastric bypass (RYGB) surgery and to investigate the added value of computed tomography angiography (CTA) for diagnosing internal herniation.Materials and MethodsA cadaver study was performed to investigate the manifestations of internal hernias and mesenteric vascularization. Furthermore, a prospective, ethics approved study with retrospective interpretation was conducted. Ten patients, clinically suspected for internal herniation, were prospectively included. After informed consent was obtained, these subjects underwent abdominal CT examination, including additional arterial phase CTA. All subjects underwent diagnostic laparoscopy for suspected internal herniation. The CTA was used to create a 3D reconstruction of the mesenteric arteries and surgical staples (3D CTA). The 3D CTA was interpreted, taking into account the presence and type of internal hernia that was found upon laparoscopy.ResultsCadaveric analysis demonstrated the complexity of internal herniation. It also confirmed the expected changes in vascular structure and surgical staple arrangement in the presence of internal herniation. 3D CTA studies of the subjects with active internal hernias demonstrated remarkable differences when compared to control 3D CTA studies. The blood supply of herniated intestinal limbs in particular showed abnormal trajectories. Additionally, enteroenterostomy staple lines had migrated or altered orientation.Conclusion3D CTA is a promising technique for diagnosing active internal hernias. Our findings suggest that for diagnosing internal hernias, focus should probably shift from routine abdominal CT examination towards the 3D assessment of the mesenteric vasculature and surgical staples.

Recent updates on echocardiography and ultrasound for Kawasaki disease: beyond the coronary artery

Kawasaki disease (KD) is a systemic vasculitis with a predilection for damage to the coronary arteries. In the acute phase, clinical decision making for KD relies on the measurements of the coronary z-score obtained by 2-dimensional echocardiography (2DE). In the convalescent phase, KD patients with coronary artery abnormalities (CAAs) eventually show arteriosclerotic vascular remodeling characterized by marked intimal proliferation and neoangiogenesis after KD vasculitis, which often induces myocardial ischemia. To date, several well-established surrogate markers including dobutamine stress echocardiography (DSE), the carotid intima-media thickness (CIMT) and flow-mediated dilatation (FMD), have been made available for risk assessment and the prediction of cardiovascular disease (CVD) in KD patients. Additionally, the use of carotid contrast-enhanced ultrasonography (CEUS), has enabled the visualization and quantification of the adventitial vasa vasorum (VV) network, assessing active vascular remodeling at remote arterial sites in KD patients with CAAs. However, there was no evidence of major vascular structural changes in KD patients in whom CAAs had never been detected. Thus, assessment of multiple modalities using 2DE may provide direct information not only on the vascular health but also on the stratification of the risk of CVD in KD patients with CAAs.

Vascular abnormalities in the placenta of Chst14-/- fetuses: implications in the pathophysiology of perinatal lethality of the murine model and vascular lesions in human CHST14/D4ST1 deficiency.

Collagen is one of the most important components of the extracellular matrix that is involved in the strength of tissues, cell adhesion and cell proliferation. Mutations in several collagen and post-translational modification enzyme genes cause Ehlers-Danlos syndrome (EDS) characterized by joint and skin hyperextensibility as well as fragility of various organs. Carbohydrate sulfotransferase 14/dermatan 4-O-sulfotransferase-1 (CHST14/D4ST1) is a critical enzyme for biosynthesis of dermatan sulfate, a side chain of various proteoglycans including biglycan that regulates collagen fibrils through their interaction. Mutations in CHST14 were found to cause a new form of EDS, named musculocontractural type EDS (mcEDS-CHST14). Large subcutaneous hematomas are one of the most serious complications accompanied by decreased quality of life and potential lethality. In this study, Chst14 gene-deleted mice were expected to be an animal model of the vascular abnormalities of mcEDS-CHST14. However, only limited numbers of adult mice were generated because of perinatal lethality in most Chst14 gene-deleted homozygote (Chst14-/-) mice. Therefore, we investigated the placentas of these fetuses. The placentas of Chst14-/- fetuses showed a reduced weight, alterations in the vascular structure, and ischemic and/or necrotic-like changes. Electron microscopy demonstrated an abnormal structure of the basement membrane of capillaries in the placental villus. These findings suggest that Chst14 is essential for placental vascular development and perinatal survival of fetuses. Furthermore, placentas of Chst14-/- fetuses could be a useful model for vascular manifestations in mcEDS-CHST14, such as the large subcutaneous hematomas.

Systemic sclerosis.

Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by vasculopathy and tissue fibrosis of the skin and various internal organs. A series of genetic and epidemiological studies have demonstrated that SSc onset is determined by the accumulation of predisposing factors related to environmental influences, while genetic factors affect the susceptibility to and the severity of this disease. This notion has been confirmed by recent advance in animal models. The initial trigger of SSc is believed to be autoimmune attacks to endothelial cells, which occur in individuals with the genetic susceptibility to autoimmune diseases and/or the cumulative exposure to certain SSc-related environmental influences. Then, endothelial cells are aberrantly activated or damaged, leading to the development of vascular structural changes, such as destructive vasculopathy and proliferative obliterative vasculopathy, and tissue fibrosis. In parallel, inflammatory cells activate SSc fibroblasts and modify the metabolism of extracellular matrix by soluble factors and autoantibodies. Prior to or during these processes, SSc fibroblasts acquire the ability to selectively respond to profibrotic growth factors and cytokines, persistently producing excessive amount of extracellular matrix. SSc fibroblasts also modify immune responses, at least those of CD4+ T cells, in the microenvironment through the secretion of immune regulatory molecules. Thus, various types of individually activated cells interact with each other and coordinately drive an SSc-specific disease cascade, leading to the development of unique clinical symptoms. This article provides an overview of the current understanding of the pathogenesis of SSc with the recent advance in the research field of this disease.

Evaluation of atherosclerosis risk by measurement of intima media thickness and pulse wave velocity in lichen planus patients; A prospective case-control study

Aim: Lichen planus (LP) is one of the chronic inflammatory diseases. Chronic inflammation may play an important role in the development of subclinical atherosclerosis. In this study, we aimed to investigate the relationship between LP and atherosclerosis by using carotid intima media thickness (CIMT) and pulse wave velocity (PWV) measurements.Methods: A controlled study is designed, two groups were formed as LP and control group. Forty LP patients (32 female and 8 male; mean age 44.6±1.2 years) and 40 healthy (control) individuals (32 female and 8 male; mean age 41.2±0.9 years) enrolled in the study. Individuals with atherosclerotic risk factors were excluded from the study for both groups. Demographic and biochemical data were recorded for both groups. CIMT and PWV measurements were compared between healthy and LP patients. Results: Maximum and average CIMT values in LP patients were significantly higher than the control group (Right maximum CIMT; 0.77±0.01 vs. 0.74±0.01, p=0.01, Left maximum CIMT; 0.80±0.01 vs. 0.76±0.01, p=0.011, Right average CIMT; 0.65±0.01 vs. 0.63±0.01, p=0.039, Left average CIMT; 0.68±0.01 vs. 0.64±0.01, p=0.005, respectively). No statistically significant difference was found between LP patients and control group for PWV (6.34±0.30 vs. 6.79±0.70 respectively, p=0.131). Conclusions: Our study demonstrated that CIMT was increased in patients with LP who had no clinical evidence of heart disease. LP patients were under an increased risk of subclinical atherosclerotic vascular dysfunction and structural changes.

Arterial Thickness and Stiffness Are Independently Associated with Left Ventricular Strain

The aim of this study was to examine the association between myocardial strain and arterial thickness and stiffness in young adults. Increased common carotid artery intima media thickness and peripheral arterial stiffness are known to precede coronary artery disease and cardiovascular (CV) events such as myocardial infarction and congestive heart failure. However, subclinical cardiac dysfunction can be detected in high-risk adults by myocardial strain echocardiography. The authors hypothesized that increased carotid artery intima media thickness would be associated with abnormal myocardial strain in young subjects who had obesity and type 2 diabetes mellitus. CV risk factors were collected in 338 young adults participating in a prospective, cross-sectional study. The CV parameters collected included intima-media thickness, peripheral arterial stiffness by brachial distensibility, and myocardial strain and strain rate. General linear models were constructed to determine if vascular structure and function measures were independently associated with myocardial strain and strain rate. A linear relationship was found between global longitudinal strain obtained from the four-chamber view and global strain rate in systole and carotid intima-media thickness (four-chamber global longitudinal strain: β=3.0, CV risk factor-adjusted R2=0.34; global strain rate in systole: β=0.0053, R2=0.21; P≤.0001) and between four-chamber global longitudinal strain and lower brachial distensibility (β=-0.42, R2=0.22; P<.001). Adverse changes in vascular structure and function are simultaneously present with reduced myocardial systolic function.

Temporal gradient during famous face naming is associated with lower cerebral blood flow and gray matter volume in aging

ObjectiveEvidence suggests that famous face naming may be a cognitive ability especially sensitive to the early pathological processes of Alzheimer's disease (AD) and that those at risk for AD may demonstrate a Ribot temporal gradient (RTG), characterized by better performance for naming remote famous faces than for naming recent famous faces. Reductions in cerebral blood flow (CBF) and gray matter volume (GMV) have been implicated in the neuropathological cascade of AD and show utility as biomarkers of AD risk. We examined whether a RTG during famous face naming was associated with lower CBF and/or GMV among a group of cognitively normal older adults. MethodsVoxel-wise independent samples t-tests were employed to contrast resting CBF values between those who exhibited a RTG (RTG+) during a famous face naming task and those who did not (RTG-) among a sample of 52 cognitively normal older adults (25 RTG-, 27 RTG+; mean age = 73). Groups were also compared on GMV using a voxel-wise general linear model. ResultsSignificant group differences in CBF and GMV were found, whereby the RTG+ group demonstrated reduced CBF and GMV within medial temporal lobe regions (hippocampus, parahippocampal gyrus), relative to the RTG- group. ConclusionsThis represents the first study to show that cognitively intact older adults who demonstrate a RTG during famous face naming exhibit vascular dysregulation and structural changes similar to that seen in AD risk. Findings suggest that famous face naming ability may be particularly sensitive to the very early brain changes associated with AD.

Simultaneous Imaging of Cerebrovascular Structure and Function in Hypertensive Rats Using Synchrotron Radiation Angiography.

Hypertension has a profound influence on the structure and function of blood vessels. Cerebral vessels undergo both structural and functional changes in hypertensive animals. However, dynamic changes of cerebrovasculature and the factors involved in this process are largely unknown. In this study, we explored the dynamic changes of vascular structure in hypertensive rats using novel synchrotron radiation angiography. Twenty-four spontaneously hypertensive rats (SHR) and 24 Sprague–Dawley (SD) rats underwent synchrotron radiation (SR) angiography. Each group had 8 animals. We studied the cerebral vascular changes in SHR over a time period of 3–12-month and performed quantitative analysis. No vascular morphology differences between SHR and SD rats were observed in the early stage of hypertension. The number of twisted blood vessels in the front brain significantly increased at the 9- and 12-month observation time-points in the SHR compared to the SD rats (p < 0.01). The vessel density of the cortex and the striatum in SHR was consistently higher than that in SD rats at time points of 3-, 9-, and 12-month (p < 0.001). Vascular elasticity decreased both in SHR and SD rats with aging. There were statistically significant differences in the relative vascular elasticity of extracranial/intracranial internal carotid artery, middle cerebral artery, posterior cerebral artery and anterior cerebral artery between SHR and SD rats at 12-month (p < 0.01). We concluded that the dynamic vascular alterations detected by SR angiography provided novel imaging data for the study of hypertension in vivo. The longer the course of hypertension was, the more obvious the vascular differences between the SHR and the SD rats became.

In Vitro and In Vivo Performance of Novel Spray Dried Andrographolide Loaded Scleroglucan Based Formulation for Dry Powder Inhaler.

Current therapy for pulmonary arterial hypertension (PAH) is unable to prevent progression of disease due to continuous infusions and multiple oral administrations. This resulted in the need of novel treatment which would target directly structural vascular changes that weaken blood flow through pulmonary circulation. The objective of present study was to develop spray dried (SD) formulation for dry powder inhaler (DPI) with enhanced aerosol performance and lung deposition by using novel bioactive, andrographolide (AGP) and carrier, scleroglucan (SCLG) with improved antihypertensive activity. The SDAGP formulation was evaluated for physicochemical properties and in vitro/in vivo lung deposition. Further, antihypertensive activity was studied by monocrotaline (MCT) induced rat model. The SDAGP exhibited mean median aerodynamic diameter (MMAD) and fine particle fraction (FPF) of 3.37 ± 0.47 µm and 60.24 ± 0.98%. The in vivo absorption profile of final formulation reflected increased lung deposition of AGP at the end of 24 h with no signs of inflammation and toxicity. Moreover, SDAGP formulation confirmed enhanced antihypertensive activity. The results proved use of AGP and SCLG as a novel bioactive and carrier with enhanced lung deposition and pulmonary antihypertensive activity.

Arterial stiffness as a risk factor for clinical hypertension.

In patients with uncomplicated essential hypertension, cardiac output remains within normal ranges and intravascular volume is normal or low, assuming the presence of a sufficient Windkessel effect and usual resistance and compliance calculations. However, mean circulatory pressure is elevated in these patients. In addition, vascular resistance is augmented, and most importantly, the viscoelasticity of the cardiovascular system is substantially impaired. Such considerations are essential to understanding the mechanisms behind carotid-femoral arterial stiffness, a major risk factor in individuals with hypertension. Arterial stiffness, measured from pulse wave velocity, is substantially increased in hypertension even independently of blood pressure levels. Structural vascular changes and endothelial dysfunction are consistently associated with vessel impairments in animal models of hypertension. Increased arterial stiffness has a major effect on pulse pressure (the difference between systolic and diastolic blood pressure), wave reflections, kidney function, and above all, cardiovascular risk. This increased cardiovascular risk is particularly deleterious in patients with hypertension and/or type 2 diabetes mellitus, who are at risk of both renal and cardiovascular events. In this Review, we discuss the importance of arterial stiffness in the diagnosis and management of hypertension and the need for new approaches for the treatment of hypertension in patients with or without diabetes and/or renal impairment.

Immune regulation of systemic hypertension, pulmonary arterial hypertension, and preeclampsia: shared disease mechanisms and translational opportunities.

Systemic hypertension, preeclampsia, and pulmonary arterial hypertension (PAH) are diseases of high blood pressure in the systemic or pulmonary circulation. Beyond the well-defined contribution of more traditional pathophysiological mechanisms, such as changes in the renin-angiotensin-aldosterone system, to the development of these hypertensive disorders, there is substantial clinical evidence supporting an important role for inflammation and immunity in the pathogenesis of each of these three conditions. Over the last decade, work in small animal models, bearing targeted deficiencies in specific cytokines or immune cell subsets, has begun to clarify the immune-mediated mechanisms that drive changes in vascular structure and tone in hypertensive disease. By summarizing the clinical and experimental evidence supporting a contribution of the immune system to systemic hypertension, preeclampsia, and PAH, the current review highlights the cellular and molecular pathways that are common to all three hypertensive disorders. These mechanisms are centered on an imbalance in CD4+ helper T cell populations, defined by excessive Th17 responses and impaired Treg activity, as well as the excessive activation or impairment of additional immune cell types, including macrophages, dendritic cells, CD8+ T cells, B cells, and natural killer cells. The identification of common immune mechanisms in systemic hypertension, preeclampsia, and PAH raises the possibility of new therapeutic strategies that target the immune component of hypertension across multiple disorders.

GW28-e1025 The relationship between sodium excretion and blood pressure, urine albumin, central retinal arteriolar equivalent

Many studies showed an association between dietary salt intake, blood pressure and increased CVD risk. The potential reason may be related to vascular structural and functional changes, through alterations in endothelial function. The central retinal arteriolar equivalent and urinary albumin

Changes in vascular structure in diabetic patients after 8 weeks aerobic physical exercise: a randomized controlled trial

Diabetes is a highly prevalent metabolic disease with macrovascular and microvascular complications. Insulin resistance plays a major role in the pathogenesis of atherosclerosis in type 2 diabetes patients. The risk of atherosclerosis progress in diabetes is of 2–4 orders of magnitude. Early atherosclerosis can be detected by carotid intima-media thickness (cIMT) ultrasonography. There is an inverse relationship between intima-media thickness and physical activity. The aim of this study was to investigate the effects of an 8-week aerobic exercise program on the vascular structure in different segments of the carotid artery. This study was a randomized control trial. Thirty individuals were selected out of 642 volunteers who fulfilled the inclusion criteria. They were randomly divided into aerobic exercise and control groups by a block randomization method. This study was carried out during May–October 2016 in Iran. The aerobic protocol comprised of 24 sessions of aerobic exercise on a treadmill for 30 min per session, 3 days a week. The intensity of the training protocol was 50–70% of the patient’s max heart rate. Measurements of vascular parameters were evaluated by the same person, before and after the 24-session intervention. There were no significant differences between anthropometric, sex, age, diabetic history, and cardiac ejection fraction, compared to baseline characteristics. Intima-media thickness (0.52 ± 0.12), intima-media/lumen (0.07 ± 0.02) in bulb carotid, common carotid, and internal carotid, as well as bulb wall, were reduced significantly in the training group compared to the control group after 8 weeks (p < 0.05). Twenty-four sessions of aerobic exercise improved vascular parameters in type 2 diabetics.

Three-year change in endothelin-1 and markers of vascular remodelling in a bi-ethnic South African cohort: the SABPA study.

South Africans are at high risk for developing cardiovascular disease. Endothelin-1 is known for its vasoconstrictive properties and its ability to contribute to vascular structural changes. In this study we investigated the association of change in endothelin-1 levels and change in markers implicated in vascular remodelling after 3 years. Serum endothelin-1 levels and markers of vascular remodelling such as carotid intima-media thickness, carotid cross-sectional wall area (CSWA) and arterial compliance were measured. Participants were divided into two groups according to an increase (n=185) and a decrease (n=152) in plasma endothelin-1 levels after 3 years. In partial regression analysis, the extent of endothelin-1 increase correlated positively with a change in pulse pressure and inversely with the change in arterial compliance in the group with increased endothelin-1 levels after 3 years. In the group with decreased endothelin-1 levels, the extent of decreased endothelin-1 correlated inversely with a change in CSWA. In multiple regression analysis, after splitting for race, the increase in endothelin-1 levels associated positively with the change in pulse pressure (Adj. R2=0.092; β=0.278; P=0.036) in the black participants only. In conclusion, with increased endothelin-1 levels after 3 years, the positive association between endothelin-1 and pulse pressure suggest subclinical haemodynamic changes with potential premature onset of cardiovascular disease in the black participants.

Chronic iron overload induces functional and structural vascular changes in small resistance arteries via NADPH oxidase-dependent O2[rad]− production

Iron overload leads to excessive free radical formation and induces cardiovascular dysfunction. Thus, our aim was to investigate the structural and endothelial modulation of vascular tone induced by chronic iron overload in mesenteric arteries. Rats were divided into two groups: the control (vehicle) group and the group treated with iron dextran for 28days (100mg/kg, 5days a week). Chronic iron overload altered the following morpho-physiological parameters of third-order mesenteric resistance arteries: decreased lumen and external diameters; increased wall/lumen ratio and wall thickness; decreased distensibility and increased stiffness; and increased pulse wave velocity. Additionally, iron overload increased the vasoconstrictor response in mesenteric arterial rings in vitro but did not affect the relaxation induced by acetylcholine and sodium nitroprusside. It is suggested that iron overload reduces nitric oxide bioavailability by increasing free radicals, because L-NAME did not shift the concentration-response curve to phenylephrine, but L-NAME plus superoxide dismutase shifted the curve to the left. In vitro assays with DAF-2 and DHE indicated reduced NO production and increased superoxide anion (O2−) generation in the iron-overloaded group. Furthermore, tiron, catalase, apocynin and losartan induced reduced reactivity only in iron-overloaded rats. Moreover, increased ACE activity was observed in the mesenteric resistance arteries of iron-overloaded rats accompanied by an increase in gp91phox, catalase, ERK1/2 and eNOS protein expression. In conclusion, these findings show that chronic iron overload induces structural and functional changes in resistance arteries, most likely due to a decrease in NO bioavailability resulting from an increase in O2− production by NADPH oxidase.