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Benjamin S. Frank Tracy T. Urban Karlise Lewis Suhong Tong Courtney Cassidy Max B. Mitchell Christopher S. Nichols Jesse A. Davidson 《Congenital heart disease》2019,14(3):446-453
Objective: Patients undergoing surgical repair of aortic coarctation have a 50% risk
of pathologic left ventricular remodeling (increased left ventricular mass or relative
wall thickness). Endothelin 1, ST2, galectin 3, norepinephrine and B‐natriuretic pep‐
tide are biomarkers that have been associated with pathologic LV change in adult
populations but their predictive value following pediatric coarctation repair are not
known.
Hypothesis: Biomarker levels at coarctation repair will predict persistent left ven‐ tricular remodeling at 1‐year follow up.
Design: Prospective, cohort study of 27 patients’ age 2 days‐12 years with coarcta‐ tion of the aorta undergoing surgical repair. Echocardiograms were performed pre‐ operation, postoperation, and at 1‐year follow‐up. Plasma biomarker levels were measured at the peri‐operative time points. Association between biomarker concen‐ trations and echocardiographic parameters was assessed.
Results: Neither left ventricular mass index nor relative wall thickness varied from pre‐op to post‐op. At pre‐op, relative wall thickness was elevated in 52% and left ventricular mass index was elevated in 22%; at follow‐up, relative wall thickness was elevated in 13% and left ventricular mass index was elevated in 8%. Presence of re‐ sidual coarctation did not predict left ventricular remodeling (AUC 0.59; P > .05). Multivariable receiver operating characteristic curve combining pre‐op ST2 and en‐ dothelin 1 demonstrated significant predictive ability for late pathologic left ven‐ tricular remodeling (AUC 0.85; P = .02).
Conclusions: Persistent left ventricular hypertrophy and abnormal relative wall thick‐ ness at intermediate‐term follow‐up was rare compared to previous studies. A model combining pre‐op endothelin 1 and ST2 level demonstrated reasonable accuracy at predicting persistent abnormalities in this cohort. Larger studies will be needed to validate this finding and further explore the mechanism of persistent left ventricular remodeling in this population. 相似文献
Hypothesis: Biomarker levels at coarctation repair will predict persistent left ven‐ tricular remodeling at 1‐year follow up.
Design: Prospective, cohort study of 27 patients’ age 2 days‐12 years with coarcta‐ tion of the aorta undergoing surgical repair. Echocardiograms were performed pre‐ operation, postoperation, and at 1‐year follow‐up. Plasma biomarker levels were measured at the peri‐operative time points. Association between biomarker concen‐ trations and echocardiographic parameters was assessed.
Results: Neither left ventricular mass index nor relative wall thickness varied from pre‐op to post‐op. At pre‐op, relative wall thickness was elevated in 52% and left ventricular mass index was elevated in 22%; at follow‐up, relative wall thickness was elevated in 13% and left ventricular mass index was elevated in 8%. Presence of re‐ sidual coarctation did not predict left ventricular remodeling (AUC 0.59; P > .05). Multivariable receiver operating characteristic curve combining pre‐op ST2 and en‐ dothelin 1 demonstrated significant predictive ability for late pathologic left ven‐ tricular remodeling (AUC 0.85; P = .02).
Conclusions: Persistent left ventricular hypertrophy and abnormal relative wall thick‐ ness at intermediate‐term follow‐up was rare compared to previous studies. A model combining pre‐op endothelin 1 and ST2 level demonstrated reasonable accuracy at predicting persistent abnormalities in this cohort. Larger studies will be needed to validate this finding and further explore the mechanism of persistent left ventricular remodeling in this population. 相似文献
3.
Objective: To investigate the effect of hydro-ethanolic extract of Zataria multiflora (Z. multiflora) on endothelin level, total and differential white blood cells (WBC) count of sensitized guinea pigs. Methods: Five groups of guinea pigs sensitized to ovalbumin (OA) were given drinking water alone (group S), drinking water containing three concentrations of Z. multiflora (0.2, 0.4 and 0.8 mg/mL as groups S+Z1, S+Z2 and S+Z3) and dexamethasone (group S+D), n=6 for each group. The endothelin levels as well as total and differential WBC count in blood of sensitized and control guinea pigs were evaluated using enzyme linked immunosorbent assay method, and hemocytometer and Wright-Giemsa''s staining of blood sample smear respectively. Results: Blood endothelin levels, total and most differential WBC count were increased but lymphocytes decreased in sensitized animals compared to controls (all P<0.01). In groups S+D, S+Z2 and S+Z3 endothelin level, total and differential WBC counts were significantly improved compared with group S (P<0.01). Although, all measured parameters in group S+Z1 was lower than group S+D (P<0.01), some parameters in group S+Z3 were greater than in group S+D (P<0.05 to P<0.01). Conclusion: The results showed an anti-inflammatory effect of Z. multiflora extract in sensitized guinea pigs, which may suggest a therapeutic potential for the plant on asthma. 相似文献
4.
Hale Z Toklu Judy Muller-Delp Zhihui Yang ?ehkar Oktay Yasemin Sakarya Kevin Strang Payal Ghosh Michael D Delp Philip J Scarpace Kevin KW Wang Nihal Tümer 《Journal of cerebral blood flow and metabolism》2015,35(12):1950-1956
Overpressure blast-wave induced brain injury (OBI) leads to progressive pathophysiologic changes resulting in a reduction in brain blood flow, blood brain barrier breakdown, edema, and cerebral ischemia. The aim of this study was to evaluate cerebral vascular function after single and repeated OBI. Male Sprague-Dawley rats were divided into three groups: Control (Naive), single OBI (30 psi peak pressure, 1 to 2 msec duration), and repeated (days 1, 4, and 7) OBI (r-OBI). Rats were killed 24 hours after injury and the basilar artery was isolated, cannulated, and pressurized (90 cm H2O). Vascular responses to potassium chloride (KCl) (30 to 100 mmol/L), endothelin-1 (10−12 to 10−7 mol/L), acetylcholine (ACh) (10−10 to 10−4 mol/L) and diethylamine-NONO-ate (DEA-NONO-ate) (10−10 to 10−4 mol/L) were evaluated. The OBI resulted in an increase in the contractile responses to endothelin and a decrease in the relaxant responses to ACh in both single and r-OBI groups. However, impaired DEA-NONO-ate-induced vasodilation and increased wall thickness to lumen ratio were observed only in the r-OBI group. The endothelin-1 type A (ETA) receptor and endothelial nitric oxide synthase (eNOS) immunoreactivity were significantly enhanced by OBI. These findings indicate that both single and r-OBI impairs cerebral vascular endothelium-dependent dilation, potentially a consequence of endothelial dysfunction and/or vascular remodelling in basilar arteries after OBI. 相似文献
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目的:观察氧自由基损害和血管内皮功能失调与高血压发生的关系及瑞舒伐他汀干预的影响。方法将8只Wistar -Kyoto 大鼠(WKY)作为正常对照组;32只自发性高血压(SHR)大鼠,随机分为瑞舒伐他汀低剂量组3.125 mg/(kg· d)、瑞舒伐他汀中剂量组6.25 mg/(kg· d)、瑞舒伐他汀高剂量组12.5 mg/(kg· d)和SHR 对照组,每组8只。给药大鼠分别每日给予不同剂量瑞舒伐他汀+1 mL蒸馏水灌胃;SHR 对照组给予相同容积的蒸馏水灌胃,测量血压。4周停药,3天后麻醉状态下提取心肌组织,用比色法检测SOD、MDA、NO 的水平,免疫组化法测定ET 的表达,PCR 法测定SODmRNA 的水平。结果自发性高血压大鼠SOD 活力、SODmRNA 表达、NO 含量下降,MDA 含量、ET -1的表达增强,与正常对照组比较,P <0.05。瑞舒伐他汀干预后上述指标均有改善(P <0.05),且呈剂量相关性。瑞舒伐他汀干预后SHR 大鼠血压下降,但无剂量相关性。结论 SHR 大鼠存在氧化应激反应的增强,瑞舒伐他汀可通过降低氧化应激反应,改善血管内皮功能、降低血压。 相似文献
7.
Zareen Amtul Carmen Frías Jasmine Randhawa David J. Hill Edith J. Arany 《The Journal of comparative neurology》2020,528(1):52-64
Large cerebral infarctions are major predictors of death and severe disability from stroke. Conversely, data concerning these types of infarctions and the affected adjacent brain circuits are scarce. It remains to be determined if the co-morbid concurrence of large infarct and β-amyloid (Aβ) toxicity can precipitate the early development of dementia. Here, we described a dose-dependent effect of a unilateral striatal injection of vasoconstrictive endothelin-1 (ET-1) along with Aβ toxicity on CNS pathogenesis; driven by the anatomical and functional networks within a brain circuit. After 21 days of treatment, a high dose (60 pmol) of ET-1 (E60) alone caused the greatest increase in neuroinflammation, mainly in the ipsilateral striatum and distant regions with synaptic links to the striatal lesion such as white matter (subcortical white matter, corpus callosum, internal capsule, anterior commissure), gray matter (globus pallidus, thalamus), and cortices (cingulate, motor, somatosensory, entorhinal). The combined E60 + Aβ treatment also extended perturbation in the contralateral hemisphere of these rats, such as increased deposition of amyloid precursor protein fragments associated with the appearance of degenerating cells and the leakage of laminin from the basement membrane across a compromised blood–brain barrier. However, the cerebral damage induced by the 6 pmol ET-1 (E6), Aβ and E6 + Aβ rats was not detrimental enough to injure the complete network. The appreciation of the causal interactions among distinct anatomical units in the brain after ischemia and Aβ toxicity will help in the design of effective and alternative therapeutics that may disassociate the synergistic or additive association between the infarcts and Aβ toxicity. 相似文献
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9.
内皮素(Endothelin, ET)是一种由21个氨基酸组成的生物活性物质。它主要由内皮细胞合成,具有非常强烈的收缩血管的生物活性。近年来研究发现除了具有强烈缩血管作用,同时内皮素也具有诱导血管生成、促分化、促细胞有丝分裂和类细胞生长因子的性质。研究文献发现人有3种内皮素亚型(ET-1、ET-2、ET-3),这三个异构肽的生物活性有一定差异,ET-1的作用最强,ET-3最弱。内皮素分子通过内皮素受体(ETRs)发挥其生理和病理作用。内皮素受体被发现广泛地表达于动物的心血管系统、神经系统和胃肠道之中。内皮素受体A(ETA)和内皮素受体B(ETB)有共同的信号转导通路。同时,ETB激活后还能促进PLA2激活。研究还发现内皮素与良恶性肿瘤有广泛的联系。 相似文献
10.
Fernando F. Migone Robert G. Cowan Rebecca M. Williams Kiersten J. Gorse Warren R. Zipfel Susan M. Quirk 《Proceedings of the National Academy of Sciences of the United States of America》2016,113(8):2294-2299
Rupture of the ovarian follicle releases the oocyte at ovulation, a timed event that is critical for fertilization. It is not understood how the protease activity required for rupture is directed with precise timing and localization to the outer surface, or apex, of the follicle. We hypothesized that vasoconstriction at the apex is essential for rupture. The diameter and blood flow of individual vessels and the thickness of the apical follicle wall were examined over time to expected ovulation using intravital multiphoton microscopy. Vasoconstriction of apical vessels occurred within hours preceding follicle rupture in wild-type mice, but vasoconstriction and rupture were absent in Amhr2cre/+SmoM2 mice in which follicle vessels lack the normal association with vascular smooth muscle. Vasoconstriction is not simply a response to reduced thickness of the follicle wall; vasoconstriction persisted in wild-type mice when thinning of the follicle wall was prevented by infusion of protease inhibitors into the ovarian bursa. Ovulation was inhibited by preventing the periovulatory rise in the expression of the vasoconstrictor endothelin 2 by follicle cells of wild-type mice. In these mice, infusion of vasoconstrictors (either endothelin 2 or angiotensin 2) into the bursa restored the vasoconstriction of apical vessels and ovulation. Additionally, infusion of endothelin receptor antagonists into the bursa of wild-type mice prevented vasoconstriction and follicle rupture. Processing tissue to allow imaging at increased depth through the follicle and transabdominal ultrasonography in vivo showed that decreased blood flow is restricted to the apex. These results demonstrate that vasoconstriction at the apex of the follicle is essential for ovulation.During ovulation in typically mono-ovulatory species such as humans, as well as in poly-ovulatory species such as rodents, the oocyte is released from the preovulatory follicle by extrusion through a rupture site on the outer surface, or apex, of the follicle, which protrudes from the surface of the ovary (1). Precise timing and accurate spatial localization of rupture at the apex are essential to allow capture of the oocyte by a hormonally primed oviduct where fertilization occurs, but the mechanisms involved are not yet understood. The rupture site breaches multiple layers of cells and their associated extracellular matrix and basement membranes (2). These include the single layer of epithelial cells that covers the surface of the ovary, the basement membrane that supports it, and the multiple cell layers comprising the wall of the preovulatory follicle. The outer wall of the ovarian follicle contains androgen-secreting theca cells and extensive vasculature. This vasculature consists of an inner and an outer plexus of capillaries with associated arterioles and venules that supply nutrients to the entire follicle (3–5). Underlying the theca and separated from it by a basement membrane is the avascular granulosa cell layer that serves as the major source of estrogen. The oocyte resides in the center of the follicle surrounded by multiple layers of specialized granulosa cells known as “cumulus cells.” In a mature preovulatory follicle, formation of a fluid-filled antral cavity separates the oocyte–cumulus complex from the mural granulosa cells that form the wall of the follicle except at a region known as the “stalk,” which connects the oocyte–cumulus complex to the antral granulosa cells of the follicle wall. At ovulation the oocyte is released from the follicle in association with attached cumulus cells.The preovulatory release of surge levels of luteinizing hormone (LH) from the anterior pituitary acts on receptors in the follicle to trigger events critical for the rupture and remodeling of the follicle and differentiation of granulosa and theca cells into progesterone-producing cells of the corpus luteum. The cumulus cells are induced to secrete a mucoelastic extracellular matrix which causes loosening of contacts between granulosa cells and between granulosa cells and the oocyte, a process known as “cumulus expansion,” which is essential for ovulation (1). Expression of proteases belonging to several major families, including the matrix metalloproteinase, plasminogen activator/plasmin, and ADAMTS (a disintegrin and metalloproteinase with thrombospondin-like motifs) families, increases. Simultaneously, follicle cells express protease inhibitors such as tissue inhibitors of metalloproteinases (TIMPs 1–4) and plasminogen activator inhibitors (PAI 1–3) (6, 7). The increase in protease activity is essential for rupture of the follicle and for the breakdown of the basement membrane separating theca and granulosa cells to allow the ingrowth of blood vessels to establish the corpus luteum. The mechanisms that regulate the balance of protease and protease inhibitor activity in the follicle to allow precise rupture at the apex while protecting most of the follicle structure from protease activity are not understood (1, 6, 7).We postulated that vasoconstriction of vessels within the theca at the apex of the follicle is required to promote follicle rupture. Our first approach was to examine mice with conditional expression of a dominant active allele of smoothened (SMO), the transmembrane protein that relays signaling by the hedgehog (HH) pathway. In these Amhr2cre/+SmoM2 mice, preovulatory follicles develop normally in many respects, including changes in the expression of critical genes in response to the preovulatory LH surge (8, 9). However, follicles fail to rupture, and oocytes remain trapped as the follicles luteinize. The major ovarian phenotype in these mice is a pronounced deficiency of vascular smooth muscle (VSM) surrounding vessels in the theca cell layer, whereas other vessels that are present throughout the stroma of the ovary have normal maturation with VSM. Because VSM is required for vasoconstriction, the mice provided a model to test whether failure of vasoconstriction contributes to anovulation. In additional experiments with wild-type mice, we blocked the increase in the expression of endothelin 2 (Edn2) by granulosa cells that normally occurs within hours before follicle rupture (10, 11). Because EDN2 is a potent vasoconstrictor, this approach allowed us to test the effect on follicle rupture of inhibiting vasoconstriction versus treatment with exogenous compounds to restore vasoconstriction. In addition, treatment of wild-type mice with EDN2 receptor antagonists was used to test the role of EDN2 in vasoconstriction and rupture. Vasoconstriction and changes in the follicle wall were monitored repeatedly relative to the time of ovulation using intravital multiphoton microscopy. 相似文献