Search

Aristolochic acid nephropathy (AAN) is characterized by interstitial fibrosis, proximal tubular atrophy, and hypoxia. A correlation between a reduced peritubular capillary density and the severity of fibrosis has been demonstrated. As calcium, redox and energetic homeostasis are crucial in maintaining endothelial cell function and survival, we aimed to investigate AA-induced disturbances involved in endothelial cell injury. Our results showed a cytotoxic effect of AA on EAhy926 endothelial cells. Exposure of aortic rings to AA impaired vascular relaxation to Acetylcholine (ACh). Increased levels of intracellular reactive oxygen species (ROS) were observed in cells exposed to AA. Pre-treatment with antioxidant N-acetyl cysteine inhibited AA-induced cell death. Superoxide dismutase resulted in restoring ACh-induced relaxation. An increase in intracellular calcium level ([Ca2+]i) was observed on endothelial cells. Calcium chelators BAPTA-AM or APB, a specific inhibitor of IP3R, improved cell viability. Moreover, AA exposure led to reduced AMP-activated protein kinase (AMPK) expression. AICAR, an activator of AMPK, improved the viability of AA-intoxicated cells and inhibited the rise of cytosolic [Ca2+]i levels. This study provides evidence that AA exposure increases ROS generation, disrupts calcium homeostasis and decreases AMPK activity. It also suggests that significant damage observed in endothelial cells may enhance microcirculation defects, worsening hypoxia and tubulointerstitial lesions., info:eu-repo/semantics/published

Recent international guidelines on the management of aortic root disease mention “aortic annuloplasty” in combination with aortic root remodeling as part of a class I indication for management of aortic root aneurysm (1). The remodeling technique provides physiological cusp movement within three reconstructed neo-sinuses, which permits root expansibility through the interleaflet triangles. We have developed a standardized aortic valve and root repair protocol involving a physiological reconstruction of the aortic root using the remodeling technique, cusp effective height resuspension, and a subvalvular external aortic ring annuloplasty (Figure 1). Open in a separate window Figure 1 Remodeling root repair with external aortic ring annuloplasty (drawing with kind permission of Dr. Pavel Zacek).

Background The aim of this study was to assess effectiveness, stability, position, and expansibility of an expansible aortic annuloplasty ring with computed tomography (CT). Methods Ten men (median age 51 years) scheduled for aortic root remodeling with implantation of external annuloplasty ring underwent contrast-enhanced CT of the aortic root preoperatively, postoperatively, and at a median of 21 months after operation. A reconstructed transverse double oblique view of the aortic base (AB) and of the new defined annuloplasty ring base (ARB; plane of the lower edge of the ring) in systole and diastole were obtained. The diameters, perimeter, and area were measured. In addition, the distances between AB and ARB in the nadir of each sinus were measured. Results We found 12% reduction of the postoperative AB and 19% of ARB perimeter in both systole ( p = 0.004, p p = 0.001, p p = 0.002, p = 0.001, respectively) and 33% reduction of the ARB area in systole and 32% in diastole ( p Conclusions This study demonstrates imaging evidence of the effectiveness, stability, and pulsatility of the annuloplasty ring in aortic root remodeling in follow-up and describes the exact position of the ring at the base of the aortic root.

Panax notoginseng, a traditional Chinese herbal medicine, has been used for the treatment of cardiovascular diseases. The main bioactive components of this species are Panax notoginseng saponins (PNS). The present study aimed to investigate the effects of PNS and five of its main components (ginsenosides Rg1, Re, Rb1 and Rd, and notoginsenoside R1) on rat aorta rings pre-contracted with norepinephrine (NE) and to determine the underlying mechanism of action. Isolated aorta rings (with or without intact endothelium) from adult male Wistar rats were stimulated with NE to induce vasoconstriction, and subsequently treated with different concentrations of PNS and its five main components (Rg1, Re, Rb1, R1 and Rd) separately. This procedure was repeated after pre-incubation with the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and the cyclooxygenase (COX) inhibitor indomethacin (INDO), in order to elucidate the mechanism of action of PNS and its components. The results demonstrated that PNS and the components Rg1, Re, Rb1 and R1, but not Rd, induced vessel relaxation in a concentration-dependent manner when the endothelium lining was intact. NO synthase inhibitor L-NAME and guanylate cyclase inhibitor ODQ attenuated the diastolic effects of PNS, Rg1, Re, Rb1 and R1 in aortic rings with intact endothelium. By contrast, INDO, a known COX inhibitor weakened the vasodilation effects of PNS, Re and Rb1 but demonstrated no effect on Rg1 and R1. In conclusion, PNS and two of its main components (Re and Rb1) exert vasodilating effects through the NO and COX pathways.

Nonalcoholic steatohepatitis (NASH) is associated with an increased risk of developing cardiovascular complications and mortality, suggesting that treatment of NASH might benefit from combined approaches that target the liver and the cardiovascular components of NASH. Using genetic and pharmacologic approaches, we show that G protein-coupled bile acid-activated receptor 1 (GPBAR1) agonism reverses liver and vascular damage in mouse models of NASH. NASH is associated with accelerated vascular inflammation representing an independent risk factor for development of cardiovascular diseases and cardiovascular-related mortality. GPBAR1, also known as TGR5, is a G protein-coupled receptor for secondary bile acids that reduces inflammation and promotes energy expenditure. Using genetic and pharmacologic approaches, we investigated whether GPBAR1 agonism by 6β-ethyl-3α,7β-dihydroxy-5β-cholan-24-ol (BAR501) reverses liver and vascular damage induced by exposure to a diet enriched in fat and fructose (HFD-F). Treating HFD-F mice with BAR501 reversed liver injury and promoted the browning of white adipose tissue in a Gpbar1-dependent manner. Feeding HFD-F resulted in vascular damage, as shown by the increased aorta intima-media thickness and increased expression of inflammatory genes (IL-6,TNF-α, iNOS, and F4/80) and adhesion molecules (VCAM, intercellular adhesion molecule-1, and endothelial selectin) in the aorta, while reducing the expression of genes involved in NO and hydrogen sulfide generation, severely altering vasomotor activities of aortic rings in an ex vivo assay. BAR501 reversed this pattern in a Gpbar1-dependent manner, highlighting a potential role for GPBAR1 agonism in treating the liver and vascular component of NASH.-Carino, A., Marchianò, S., Biagioli, M., Bucci, M., Vellecco, V., Brancaleone, V., Fiorucci, C., Zampella, A., Monti, M. C., Distrutti, E., Fiorucci, S. Agonism for the bile acid receptor GPBAR1 reverses liver and vascular damage in a mouse model of steatohepatitis.

The purpose of this research is to segment the aortic annulus, present in cardiac computed tomography images, from a computational strategy generated using global similarity enhancement, vector least squares support machines and a segmentation technique named region growing. This enhancement is obtained by applying the following steps: a) Obtain an image of similarity by calculating the absolute value of the arithmetic subtraction that considers the original image and an image of contours. The image of contours is obtained by processing the original image with a filter based on the magnitude of the gradient. b) Is is processed with a Gaussian filter, generating a smoothed similarity image. On the other hand, considering the smoothed similarity image, the least squares support machines are used both to construct two cutting planes (that isolate the aortic artery) and to detect the coordinates of a seed voxel. In order to produce the morphology of the aortic valve annulus, the seed voxel initializes the technique of growth of regions during the segmentation process. From this morphology, some useful quantitative descriptors are calculated for the aortic ring characterization.

Mitral valve repair is well developed, and it allows for successful reconstruction of selected rheumatic valve pathologies. Rheumatic aortic valve repair also has been successful, using techniques such as Nodular unfolding. Aortic ring annuloplasty is currently available, and when used in conjunction with appropriate leaflet procedures, it could promote rheumatic repair by restoring annular geometry and facilitating leaflet reconstruction. This report describes rheumatic double valve repair in a patient with rheumatic dysfunction of both the aortic and mitral valves.

© 2018, The Author(s). The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.

Annular stabilization techniques in bicuspid aortic valve (BAV) repair include valve-sparing root reimplantation (VSRR), external subannular aortic ring (ESAR), and subcommissural annuloplasty (SCA). Unlike VSRR that offers neoroot creation, ESAR and SCA offer annular reduction only. We compared long-term functional outcomes to understand BAV repair durability.From 2004 to 2017, 137 patients underwent Sievers type I BAV repair (VSRR, n = 54; ESAR, n = 22; SCA, n = 51). Prospectively maintained BAV repair database was queried for clinical and functional outcomes. Data were analyzed by logistic regression, threshold regression, multistate survival, and transition models for BAV repair durability.VSRR patients had larger preoperative sinus dimensions (p0.001), but mean preoperative annulus size was similar for VSRR, ESAR, and SCA (29.3 ± 3.7 mm, 29.8 ± 3.8 mm, and 29.7 ± 3.8mm, respectively; p = 0.807). Degree of annular reduction (p = 0.280) was comparable between the groups. Intraoperative postrepair freedom from aortic insufficiency (AI) 1+ or greater was 100% across the entire cohort. By logistic regression, important predictors of recurrent AI (1+ and ≥2+) were preoperative annulus of 30 mm or more for SCA. Threshold regression confirmed annulus of 30 mm or more as risk factor for recurrent AI of 1+ or greater for SCA. Risk to relapse from no AI to AI 1+ was equal between the groups; however, once AI 1+ was reached, there was a 2.5-fold increased risk for patients with annulus of 30 mm or more who underwent SCA to progress to recurrent AI of 2+ or greater.VSRR is associated with improved longitudinal BAV durability compared with SCA. Preoperative annulus diameter of 30 mm or more is associated with increased recurrent AI, especially for SCA patients. For annular indications, ESAR might offer comparable functional outcomes with VSRR; however, further follow-up is critical.

Background Curcumin (diferuloylmethane) has been associated with the inhibition of angiogenesis, as well as the prevention of cancers and inflammatory processes. The aim of this study was to assess the efficacy of curcumin in suppressing angiogenesis in the cultured endothelial cells of rat aortic rings. Methods Eight-week-old male Wistar rats were randomized into five groups each with a different treatment and cell culturing paradigm: controls cultured in the absence of VEGF (vascular endothelial growth factor) (C), controls cultured in the presence of VEGF (C-V), controls treated with curcumin and then cultured in media lacking VEGF (C-TC), diabetics cultured in media supplemented with VEGF (D-V) and diabetics treated with curcumin and then cultured in media supplemented with VEGF (D-V-TC). Each group consisted of 8 animals. Diabetes was induced in by streptozotocin (STZ; 60 mg/kg body weight, IV). After 8 weeks, animals were sacrificed and their aortas were excised. Ring-shaped explants were embedded in a 96-well culture plate. Angiogenesis response was measured by counting the number of primary microtubules in each well. Results Optic microscopy revealed that the D-V group had the highest number of microvessels, while angiogenesis was not observed in the C or C-TC groups. The number of primary microtubules was significantly lower in the D-V-TC group compared to the D-V group (P, Graphical abstract

Gamabufotalin (CS-6), a main active compound isolated from Chinese medicine Chansu, has been shown to strongly inhibit cancer cell growth and inflammatory response. However, its effects on angiogenesis have not been known yet. Here, we sought to determine the biological effects of CS-6 on signaling mechanisms during angiogenesis. Our present results fully demonstrate that CS-6 could significantly inhibit VEGF triggered HUVECs proliferation, migration, invasion and tubulogenesis in vitro and blocked vascularization in Matrigel plugs impregnated in C57/BL6 mice as well as reduced vessel density in human lung tumor xenograft implanted in nude mice. Computer simulations revealed that CS-6 interacted with the ATP-binding sites of VEGFR-2 using molecular docking. Furthermore, western blot analysis indicated that CS-6 inhibited VEGF-induced phosphorylation of VEGFR-2 kinase and suppressed the activity of VEGFR-2-mediated signaling cascades. Therefore, our studies demonstrated that CS-6 inhibited angiogenesis by inhibiting the activation of VEGFR-2 signaling pathways and CS-6 could be a potential candidate in angiogenesis-related disease therapy.

Introduction. Cardiac abscess is a severe complication of aortic valve endocarditis. The aortic valve ring is more commonly affected than mitral valve ring. Materials and methods. We report the case of a patient admitted to the cardiology clinic, evaluated, diagnosed and later transferred to the Infectious Disease Clinic for treatment. Results. We present the case of a patient of 72 years old, hospitalized in the cardiology clinic with symptoms and signs of heart failure. After clinical and laboratory data, it was diagnosed infective endocarditis on bicuspid aortic valve and abscess aortic ring evacuated. The patient was transferred to the infectious diseases clinic for antibiotic treatment. Conclusions. It is a complex case with multidisciplinary approach, and aortic ring abscess is a poor prognostic factor.

Reconstruction of cardiac valves is associated with reduced mortality, including in multiple valve surgery. However, multiple valve repair is still considered a challenge, even with established techniques. Recently, internal aortic ring annuloplasty has been introduced and could simplify multiple valve reconstruction. This study reports early results with double ring aortic and mitral valve repair. Three patients with bivalvular degenerative regurgitation were managed with combined aortic and mitral valve repair using double rings. Mean (±SD) age was 41 ± 21 years, preoperative left ventricular end-diastolic volume was 119 ± 53 mL/m2, and ejection fraction was 0.50 ± 0.07. Mean aortic ring diameter was 21 mm, and mitral rings averaged 32 mm. No operative mortalities or major complications were observed. No valve-related events occurred. Postoperative echo showed complete resolution of mitral and aortic regurgitation. Postoperative left ventricular end-diastolic volume decreased to 98 ± 10 mL/m2; no left ventricular outflow tract obstruction or significant transvalvular gradients were observed. Postoperative cardiac CTs showed an optimal three-dimensional configuration of aortic and mitral annuloplasty devices. This initial series demonstrated the feasibility and safety of combined aortic and mitral repair with double rings. Clinical and hemodynamic results were promising. Increasing application and more clinical experience with combined aortic and mitral double ring repair seems indicated.

Degenerative tricuspid and bicuspid aortic insufficiency are the most common etiologies in Western countries, accounting for approximately 2/3 of the cases of aortic insufficiency in the Euro Heart Survey on valvular heart disease [1–3]. It is characterized by dilation the aortic annulus, sinuses and/or sinotubular junction (STJ) diameters preventing coaptation of pliable leaflets which may also be subjected to prolapse [3–6]. Dilation of the annulus is almost constantly present in annulo-aortic ectasia and dystrophic aortic insufficiency, especially in the setting of a bicuspid valve, where an untreated diameter greater than 25–28 mm has been identified as a risk factor for immediate and long term failure of valve repair, but also in isolated aortic insufficiency (AI) [4–13].

In bicuspid aortic valve patients with nonaneurysmal root (45 mm) and severe aortic insufficiency (AI), external subannular aortic ring (ESAR) is being increasingly utilized for annular stabilization, compared with traditional subcommissural annuloplasty (SCA). To this date, there is no comparative study assessing functional equivalence or superiority of ESAR over SCA.From 2003 to 2017, 139 patients underwent type I bicuspid aortic valve repair, of which 50 patients underwent concomitant SCA and 24 underwent ESAR. Cases with suboptimal echocardiographic imaging were excluded, resulting in 38 patients in the SCA group and 20 patients in ESAR group. Intraoperative transesophageal echocardiography before and after procedure were retrospectively analyzed for 11 parameters in the functional aortic root complex.ESAR patients had larger preoperative annulus (28.3 ± 3.2 mm versus 29.8 ± 3.7 mm, p = 0.1) and left ventricular (LV) outflow tract (28.1 ± 3.5 mm versus 29.8 ± 4.0 mm, p = 0.1) diameters, with greater leaflet prolapse (3.4 ± 1.3 mm versus 4.3 ± 1.3, p = 0.02). In both groups, 100% freedom from AI greater than 1+ was achieved, with significant reduction of vena contracta (-3.0 ± 0.6 mm, p0.001; -3.2 ± 0.4 mm, p0.001) and level of eccentricity of AI jet (AI angle change: -24.3 ± 6.5 degrees, p = 0.002; -22.3 ± 7.2 degrees, p = 0.01). Reduction in LV dimensions (-7.1 ± 1.2 mm, p0.001; -8.9 ± 1.9 mm, p0.001), annulus (-3.4 ± 0.4 mm, p 0.001; -5.1 ± 2.7 mm, p0.001), LV outflow tract (-2.3 ± 0.4 mm, p0.001; -4.4 ± 0.5 mm, p0.001), and degree of leaflet prolapse (-1.6 ± 0.4 mm, p = 0.005; -2.1 ± 0.4 mm, p = 0.001) was achieved in both groups. Comparison of postprocedure outcomes showed improved mean transvalvular gradients in ESAR (11.2 ± 5.7 mm Hg versus 7.1 ± 2.5 mm Hg, p = 0.003), with similar freedom from AI.In addition to providing equivalent and excellent freedom from AI, ESAR also renders a more robust annular reduction than SCA, along with improved transvalvular gradients.

Wuluh star fruit (Averrhoa bilimbi L.) is Oxadiliaceae family which can be used as an antihypertensive drug by ethnomedicine. A. bilimbi fruit juice is proven to lower blood pressure in preclinical testing and limited phase 1 clinical trials, where the mechanism of action is through vasodilatation of blood vessels. The taste of juice fruit is very sour, but there is no information about the effect of pH increasing of juice on vasodilatation activity in blood vessels. In this research, A. bilimbi fruits were made into juice, filtered, centrifuged to get the supernatant. The pH of juice was increased by NaOH and KOH addition. Vasodilatation activity of juice was tested on isolated organs of the aortic ring endothelium. The control that used was Kreb's-Henselheit solution with a pH approaching the tested juice solution. The result showed that an increase in the pH of A. bilimbi fruit juice caused a decrease in vasodilatation activity. The type of solution to increase the pH of juice also affected the changes in vasodilatation activity. It can be concluded that the pH increasing on juice of A. bilimbi fruit can decrease vasodilatation activity on isolated organs of the aortic ring endothelium.

Objectives The study is made to describe the efficacy and safety of balloon postdilatation (BPD) for the treatment of residual aortic regurgitation (RAoR) after transcatheter aortic valve implantation (TAVI). Methods and Results A single-center observational study is made with 157 consecutive patients accepted to TAVI. The patients were divided into two groups (no BPD-period and BPD-period). Before BPD, RAoR ≥ 2 was seen in 25% of the patients in group 1 and in 29% of the patients in group 2 (P ≥ 0.593). BPD was carried out in 95% (n = 21) of the patients in group 2 with RAoR ≥ 2. Regurgitation improved one grade in 68% of the cases (n = 15), 2 grades in 14% (n = 3), and remained without change in 18% (n = 4). RAoR < 2 was achieved in 91% (n = 73) of the patients in group 2 versus 75% (n = 58) in group 1 (RR = 0.35, 95% CI 0.16–0.80, P = 0.013). We recorded no aortic ring ruptures, damage to the device or displacements. Slight central regurgitation not present before BPD was registered in one case. Conclusions BPD offers a very good safety profile and reduces RAoR in a large percentage of cases. BPD should be considered for the treatment of moderate to severe RAoR following TAVI. © 2013 Wiley Periodicals, Inc.

A number of reproducible, technically satisfactory methods are available for experimentally measuring the anti- and proangiogenic activities of vascular growth factors, hormones, peptides, and pharmaceuticals. A group of widely used in vitro and in vivo assays for angiogenesis are reviewed here. The in vitro assays are the aortic ring, sprouting, and tube formation systems and the in vivo assays are the chick chorioallantoic membrane (CAM), the zebrafish, tumor xenografts in the immunocompromised mouse, and the Matrigel plug models. Human angiogenesis cannot be entirely reproduced in a single assay system. Thus, satisfactory preclinical anti- and proangiogenesis assay results do not assure clinical efficacy. Most of the assays discussed here, however, respond predictably to standard angiogenesis inhibitors and proangiogenesis factors and are cost effective.

The development of novel thalidomide derivatives as immunomodulatory and anti-angiogenic agents has revived over the last two decades. Herein we report the design and synthesis of three chemotypes of barbituric acids derived from the thalidomide structure: phthalimido-, tetrafluorophthalimido-, and tetrafluorobenzamidobarbituric acids. The latter were obtained by a new tandem reaction, including a ring opening and a decarboxylation of the fluorine-activated phthalamic acid intermediates. Thirty compounds of the three chemotypes were evaluated for their anti-angiogenic properties in an ex vivo assay by measuring the decrease in microvessel outgrowth in rat aortic ring explants. Tetrafluorination of the phthalimide moiety in tetrafluorophthalimidobarbituric acids was essential, as all of the nonfluorinated counterparts lost anti-angiogenic activity. An opening of the five-membered ring and the accompanying increased conformational freedom, in case of the corresponding tetrafluorobenzamidobarbituric acids, was well tolerated. Their activity was retained, although their molecular structures differ in torsional flexibility and possible hydrogen-bond networking, as revealed by comparative X-ray crystallographic analyses.

Introduction: Features of an ideal cell type, that would be conducive to vascular regeneration include (1) expression of pro-angiogenic genes (2) secretion of factors that promote developing or regenerating vasculature, and (3) maintenance of pro-angiogenic properties in the microvascular niche. Hypothesis: FTM HUCPVCs, a young rich source of mesenchymal stromal-like cells (MSCs) are ideal candidates for vascular regeneration due to their high expression of pro-angiogenic factors. Methods: The paracrine angiogenic potential of 3 types of MSCs was evaluated and compared using ex vivo tissue culture of rat aortic rings. Aorta sections were embedded into Matrigel™, cells were added to transwell membranes (pore=0.1μm, EBM 2% FBS) and combined with aortic rings (Day 0). Radial network growth and total loop formation were monitored by microscopy. Endothelial networks were quantified by ImageJ TM software. p values were calculated using ANOVA. (N=3 experiments, n=3 replicates). At day 7, the MSCs were isolated from transwells, human cytokine gene expression levels were measured using human growth factor profiler qPCR array (Qiagen, normalizers: GAPDH, βACT). Ct>35 considered negligible. Results: In the transwell aortic ring assay, FTM HUCPVCs induced significantly greater network growths when compared to term HUCPVCs (p≤0.0001), BMSCs (p≤0.0001) and untreated rings (p≤0.05). Quantification of network loop formation showed that FTM HUCPVCs induced greater numbers of closed loops when compared to term HUCPVCs (p≤0.0001), BMSCs (p≤0.0001) and untreated networks (p≤0.0001). Human growth factor qPCR array showed a high expression of angiogenic factors (Ct3), and 3 downregulated genes (FGF19, FGF9, NRTN ΔCt>3) at day 7 when compared to day 1. Conclusion: Compared to older sources of MSCs, FTM HUCPVCs promote developing endothelial networks in vitro via paracrine mechanisms and maintain the high expression of pro-angiogenic factors when cultures with endothelial cells.

Objective Although the remodeling technique provides the most dynamic valve-sparing root replacement, a dilated annulus (>25 mm) is a risk factor for failure. Aortic annuloplasty aims to reduce the annulus diameter, thus increasing coaptation height to protect the repair. The results of 177 patients with remodeling and external aortic ring annuloplasty were studied. Methods Data were collected from the Aortic Valve repair InternATiOnal Registry. Preoperative aortic insufficiency grade 3 or greater was present in 79 patients (44.7%). The valve was bicuspid in 59 patients (33.3%). External annuloplasty was performed through a homemade Dacron ring (56) or a dedicated expansible aortic ring (121). Results Thirty-day mortality was 2.9% (5). Mean follow-up was 41.1 ± 36.4 months. For the whole series, freedom from valve-related reoperation, aortic insufficiency grade 3 or greater, aortic insufficiency grade 2 or greater, and major adverse valve-related events were 89.5%, 90.5%, 77.4%, and 86.6% at 7 years, respectively, with similar results for tricuspid and bicuspid valves. Since 2007, systematic use of calibrated expansible ring annuloplasty, followed 1 year later by systematic cusp effective height assessment, significantly increased 7-year freedom from valve-related reoperation, aortic insufficiency grade 3 or greater, and major adverse valve-related events up to 99.1% ± 0.9% ( P = .017), 100% ( P = .026), and 96.3% ± 1.8% ( P = .035), respectively, whereas freedom from aortic insufficiency grade 2 or greater remained unaffected (78.1% ± 7.6%). Calibrated annuloplasty and effective height assessment were identified as protective factors from reoperation: hazard ratio, 0.13; 95% confidence interval, 0.02-1.06; P = .057 and hazard ratio, 0.11; 95% confidence interval, 0.01-0.95; P = .044, respectively. Conclusions The standardization of remodeling root repair with calibrated expansible aortic ring annuloplasty and cusp effective height assessment improves valve repair outcomes.

A virtual screening approach was performed to develop novel and potent vascular endothelial growth factor receptor 2 inhibitors. The Specs database was filtered by ‘rule of five’, a pharmacophore model, and docking filter. Sixteen molecules were selected for tube formation assay, a naphthalenol group containing molecule, 12, showed good performance in the study. In the following aortic ring assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 12 was discovered to efficiently inhibit angiogenesis and tumor cell growth. It is the first time to discover naphthalenol scaffold as potent vascular endothelial growth factor receptor 2 inhibitors. Thus, a molecular dynamic simulation process was applied to discover key features of 12 in binding to vascular endothelial growth factor receptor 2. Hydrophobic interactions were discovered to play significant role in the ligand–receptor binding.

Tridax procumbens is commonly used in traditional medicine in southern part of Nigeria for the treatment of hypertension. However, the mechanism of its antihypertensive properties remains unclear. Attempts were made to investigate the properties of direct actions of aqueous extract of the leaves of T. procumbens on mechanical responses of smooth muscles in aortic ring preparations isolated from the rat. Endothelium-intact aortic rings, isolated from the normotensive rats, had been pre-contracted with noradrenaline, and cumulative addition of the aqueous extract (0.15-1.05 mg/mL) to the bathing fluid induced a concentration-dependent relaxation. Aqueous extract of T. procumbens also attenuated the contractile responses to KCl and shifted the concentration-response curve to the right. The contractile responses to serotonin were also attenuated and the concentration-response curve was shifted to the right in the presence of the extract. The results of this study indicated that aqueous leaf extract of T. procumbens possesses vasodilatory effects on the aortic smooth muscles isolated from the rat. Based on these results, a possible mechanism involved in the relaxing actions of the extract on vascular smooth muscle was discussed. The results of this study may provide a scientific basis for the use of this extract to the treatment of hypertension in Nigerian traditional medicine.

In experiments on rat aortic ring segments, lysophosphatidylcholine in concentrations of 2×10(-6), 2×10(-5), and 2×10(-4) M did not suppress the tonotropic effect of phenylephrine (6×10(-6) and 6×10(-5) M) and in concentration of 2×10(-5) M even potentiated it, which was noted for phenylephrine at a concentration of 6×10(-6) M. It was concluded that the chemomodulating effect of lysophosphatidylcholine depends on the type of receptors and cells.

This study investigated the role of netrin-1 in placental vascular development. In vitro rat aortic ring assay and in vivo Matrigel plug assay were conducted to exmaine the effect of netrin-1 on angiogenesis. Human placental microvascular endothelial cells (HPMECs) were isolated and cultured and their viability, migration and tubular formation were studied, in order to examine the effects of netrin-1. The results showed that netrin-1 potently stimulated neovascularization in a mouse Matrigel plug in vivo and the sprouting of endothelial cells in rat aortic rings in vitro. In addition, netrin-1 enhanced the viability, migration and tube formation of HPMECs. Our study suggested that netrin-1 could significantly promote the formation of blood vessels of human placenta and may be a potential target for developing new therapeutic strategies for placental vasculature-related diseases.

An efficacy and safety of valve-sparing aortic root surgery with aortic ring annuloplasty have been demonstrated in various trials. The main technical features of aortic root remodeling with external aortic ring annuloplasty are reported in the article.Эффективность и безопасность клапан-сохраняющих вмешательств на корне аорты с использованием техники ремоделирования и аннулопластики аортального клапана были продемонстрированы в ряде исследований. В статье кратко представлены основные технические моменты ремоделирования корня аорты с экзопротезированием фиброзного кольца трехстворчатого аортального клапана.

Objective: Repair of combined dystrophic mitral and aortic insufficiency (AI) remains a challenge. We report outcomes of a standardized repair approach using mitral and aortic ring annuloplasty.Met...

Since anti-angiogenic therapy has becoming a promising approach in the prevention of cancer and related diseases, the present study was aimed to examine the anti-angiogenic effect of siphonaxanthin from green alga (Codium fragile) in cell culture model systems and ex vivo approaches using human umbilical vein endothelial cells (HUVECs) and rat aortic ring, respectively. Siphonaxanthin significantly suppressed HUVEC proliferation (p < 0.05) at the concentration of 2.5 μM (50% as compared with control) and above, while the effect on chemotaxis was not significant. Siphonaxanthin exhibited strong inhibitory effect on HUVEC tube formation. It suppressed the formation of tube length by 44% at the concentration of 10 μM, while no tube formation was observed at 25 μM, suggesting that it could be due to the suppression of angiogenic mediators. The ex vivo angiogenesis assay exhibited reduced microvessel outgrowth in a dose dependent manner and the reduction was significant at more than 2.5 μM. Our results imply a new insight on the novel function of siphonaxanthin in preventing angiogenesis related diseases.

Cardiovascular malformations are commonly reported with congenital rubella (CR). We report the first case of a miniature aortic ring in an adult CR patient. 52-year-old woman with history for CR with blindness, deafness, and obesity was referred for progressive dyspnea. Physical exam was notable