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Background and Purpose: Activation of the renin‐angiotensin system, as a hallmark of hypertension and chronic kidney diseases (CKD) is the key pathophysiological factor contributing to the progression of tubulointerstitial fibrosis. LIM and senescent cell antigen‐like domains protein 1 (LIMS1) plays an essential role in controlling of cell behaviour through the formation of complexes with other proteins. Here, the function and regulation of LIMS1 in angiotensin II (Ang II)‐induced hypertension and tubulointerstitial fibrosis was investigated. Experimental Approach: C57BL/6 mice were treated with Ang II to induce tubulointerstitial fibrosis. Hypoxia‐inducible factor‐1α (HIF‐1α) renal tubular‐specific knockout mice or LIMS1 knockdown AAV was used to investigate their effects on Ang II‐induced renal interstitial fibrosis. In vitro, HIF‐1α or LIMS1 was knocked down or overexpressed in HK2 cells after exposure to Ang II. Key Results: Increased expression of tubular LIMS1 was observed in human kidney with hypertensive nephropathy and in murine kidney from Ang II‐induced hypertension model. Tubular‐specific knockdown of LIMS1 ameliorated Ang II‐induced tubulointerstitial fibrosis in mice. Furthermore, we demonstrated that LIMS1 was transcriptionally regulated by HIF‐1α in tubular cells and that tubular HIF‐1α knockout ameliorates LIMS1‐mediated tubulointerstitial fibrosis. In addition, LIMS1 promotes Ang II‐induced tubulointerstitial fibrosis by interacting with vimentin. Conclusion and Implications: We conclude that HIF‐1α transcriptionally regulated LIMS1 plays a central role in Ang II‐induced tubulointerstitial fibrosis through interacting with vimentin. Our finding represents a new insight into the mechanism of Ang II‐induced tubulointerstitial fibrosis and provides a novel therapeutic target for progression of CKD. [ABSTRACT FROM AUTHOR]

Aim: Mitochondrial dysfunction, a characteristic pathological feature of renal Ischemic/reperfusion injury (I/RI), predisposes tubular epithelial cells to maintain an inflammatory microenvironment, however, the exact mechanisms through which mitochondrial dysfunction modulates the induction of tubular injury remains incompletely understood. Methods: ESI‐QTRAP‐MS/MS approach was used to characterize the targeted metabolic profiling of kidney with I/RI. Tubule injury, mitochondrial dysfunction, and fumarate level were evaluated using qPCR, transmission electron microscopy, ELISA, and immunohistochemistry. Results: We demonstrated that tubule injury occurred at the phase of reperfusion in murine model of I/RI. Meanwhile, enhanced glycolysis and mitochondrial dysfunction were found to be associated with tubule injury. Further, we found that tubular fumarate, which resulted from fumarate hydratase deficiency and released from dysfunctional mitochondria, promoted tubular injury. Mechanistically, fumarate induced tubular injury by causing disturbance of glutathione (GSH) hemostasis. Suppression of GSH with buthionine sulphoximine administration could deteriorate the fumarate inhibition‐mediated tubule injury recovery. Reactive oxygen species/NF‐κB signaling activation played a vital role in fumarate‐mediated tubule injury. Conclusion: Our studies demonstrated that the mitochondrial‐derived fumarate promotes tubular epithelial cell injury in renal I/RI. Blockade of fumarate‐mediated ROS/NF‐κB signaling activation may serve as a novel therapeutic approach to ameliorate hypoxic tubule injury. [ABSTRACT FROM AUTHOR]

Sustained cardiac hypertrophy damages the heart and weakens cardiac function, often leading to heart failure and even death. Pathological cardiac hypertrophy has become a central therapeutic target for many heart diseases including heart failure. However, the underlying mechanisms of cardiac hypertrophy, especially the involvement of autophagy program, are still ill‐understood. Synaptotagmin‐7 (Syt7), a multifunctional and high‐affinity calcium sensor, plays a pivotal role in asynchronous neurotransmitter release, synaptic facilitation, and vesicle pool regulation during synaptic transmission. However, little is known about whether Syt7 is expressed in the myocardium and involved in the pathogenesis of heart diseases. Here we showed that Syt7 was significantly upregulated in Ang II‐treated hearts and cardiomyocytes. Homozygous syt7 knockout (syt7−/−) mice exhibited significantly attenuated cardiac hypertrophy and fibrosis and improved cardiac function. We further found that Syt7 exerted a pro‐hypertrophic effect by suppressing the autophagy process. In exploring the upstream mechanisms, microRNA (miR)‐93 was identified to participate in the regulation of Syt7 expression. miR‐93 protected hearts against Ang II‐induced hypertrophy through targeting Syt7‐autophagy pathway. In summary, our data reveal a new cardiac hypertrophy regulator and a novel hypertrophy regulating model composed of miR‐93, Syt7 and autophagy program. These molecules may serve as potential therapeutic targets in the treatment of cardiac hypertrophy and heart failure. [ABSTRACT FROM AUTHOR]

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are potential cancer biomarkers. Little is known about the role of HNRNPR, an essential member of the hnRNP family, in human tumours. This study aims to explore the potential value of HNRNPR across cancers, based on The Cancer Genome Atlas (TCGA). The expression level, mutation, DNA methylation, phosphorylation status, survival status, pathological stage, tumor mutation burden (TMB), microsatellite instability (MSI), immune cell infiltration, and immune signature related to HNRNPR were analyzed. HNRNPR expression level was increased in several types of cancer and was associated with poor prognosis, especially in liver hepatocellular carcinoma (LIHC). HNRNPR was also correlated with antitumour immunity, and associated with TMB, MSI, and immune cell activation status across cancers. Furthermore, nomograms were established to predict the prognosis of LIHC, based on HNRNPR and other clinical characteristics. Functional enrichment analysis showed the mechanisms of HNRNPR‐mediated LIHC progression. Loss‐of‐function experiments demonstrated that inhibition of HNRNPR could remarkably suppress hepatocellular carcinoma (HCC) cell proliferation, migration, invasion, and Epithelial‐Mesenchymal Transition abilities. Our study offers a comprehensive understanding of the oncogenic roles of HNRNPR across different tumours, and demonstrates that HNRNPR might foster the proliferation, migration, and invasion abilities of HCC cells. [ABSTRACT FROM AUTHOR]

Objective: To investigate the expression of triggering receptor expressed on myeloid cells 2 (TREM‐2) in the healthy and diseased tissue, including gingivitis or periodontitis, and then to assess whether it has an impact on the development of periodontitis. Methods and materials: The gingival tissues from healthy controls, gingivitis, and periodontitis underwent hematoxylin–eosin and immunohistochemical staining, and the association of TREM‐2 expression or TREM‐2+ cell counts with clinical parameters was assessed. An anti‐TREM‐2 antibody was used to block the osteoclastogenesis in vitro and during the experimental periodontitis by injection into the gingiva. The relative gene expression of TREM‐2 in different gingival tissues was analyzed by quantitative PCR. Results: In the gingival tissues of periodontitis, TREM‐2 expression and TREM‐2+ cell counts were significantly higher than those of gingivitis and healthy controls (p<0.05). In the group of periodontitis showing moderate signs, the gingival tissues displayed significantly lower TREM‐2 expression, in contrast with the group with advanced periodontal symptoms (p < 0.05). Consistently, blocking TREM‐2 significantly decreased osteoclast formation both in vitro and in vivo (p < 0.05). Conclusion: Increased TREM‐2 expression and TREM‐2+ cells were positively associated with the development of periodontitis. Osteoclast differentiation and stimulating alveolar bone loss were partly relied on TREM‐2, which could be a target to be blocked for attenuating osteoclastogenesis in periodontitits. [ABSTRACT FROM AUTHOR]

Minerals such as calcium carbonates and calcium phosphates are often used as drug protein carriers, which are urgently required for drug protein‐based therapy, due to their high biocompatibility. However, their performance is constrained by some obstacles, such as the low loading capacity and short circulation half‐life. Inspired by the in vivo growth of biominerals via the soluble protein‐stabilized amorphous precursors, herein drug proteins are directly used to stabilize amorphous carbonated calcium phosphate (ACCP) in a controlled mineralization environment. The bioactivity of the drugs in the ACCP carrier is preserved due to the mild synthesis condition. The intrinsically high absorption capability of the ACCP nanoparticles (NPs) leads to an ultra‐high protein loading capacity. In addition, the amorphous nature of the carrier ensures the homogeneous distribution of the protein molecules in the carrier, by which the drugs exhibit long‐term release in vitro. The effectiveness of this strategy by the high osteogenic ability of insulin‐like growth factor‐1 loaded ACCP NPs is demonstrated. Therefore, this biomimetic strategy provides a promising nanoplatform for drug protein‐based applications. [ABSTRACT FROM AUTHOR]

Development of an efficient, stereoselective, sustainable synthesis of chiral aryl β‐hydroxy α‐amino acids and their derivatives is of paramount importance, owing to the broad utility of these molecules in pharmaceutical application and asymmetric synthesis. We report a systematic study on ketoreductase (KRED)‐catalyzed dynamic reductive kinetic resolution (DYRKR) of aryl α‐amino β‐keto esters 6, furnishing 20 structurally diverse chiral syn‐aryl β‐hydroxy α‐amino esters (syn‐(2S,3R)‐7) in moderate‐to‐excellent isolated yield (up to 93%), along with moderate‐to‐excellent diastereoselectivity (up to >99 : 1 dr) and excellent enantioselectivity (mostly >99% ee). The practical synthesis potential of our developed method was showcased by the asymmetric, chemo‐enzymatic total synthesis of thiamphenicol (1). [ABSTRACT FROM AUTHOR]

Objective: The study aimed to investigate the involvement of astrocytes in the medullary dorsal horn (MDH) in the orofacial hyperalgesia induced by experimental tooth movement (ETM) and related mechanism. Materials and Methods: Experimental tooth movement was produced with nickel‐titanium alloy closed‐coil spring fixed between the left maxillary first molar and the left upper incisor. Fluorocitrate was administrated through medullary subarachnoid at 3 days after ETM. Pressure pain threshold (PPT) in masseter cutaneous area was measured. The expression of glial fibrillary acidic protein (GFAP) and c‐Fos in MDH was measured using immunofluoroscence staining. The expression of interleukin‐1β (IL‐1β) and phosphorylated N‐methyl‐D‐aspartic acid (NMDA) receptor subunit NR1 (p‐NR1) was measured with Western blotting. Results: Experimental tooth movement‐induced orofacial hyperalgesia from 1 to 9 days as the PPT was significantly reduced (P <.05). Immunofluoroscence staining showed that the expression of c‐Fos in MDH was dramatically upregulated at 1 day and 3 days after ETM, while GFAP expression with both immunofluoroscence staining and Western blotting was significantly enhanced at 3 days and 7 days after ETM. Western blotting analysis indicated that the expression of IL‐1β and p‐NR1 in MDH was significantly enhanced at 3 days after ETM. Furthermore, we found that fluorocitrate administration at 3 days after ETM could markedly suppress the expression of c‐Fos, GFAP, IL‐1β and p‐NR1 and attenuate the reduction of PPT induced by ETM. Conclusion: Astrocyte activation in MDH is involved in the mechanical hyperalgesia, and the subsequent upregulated IL‐1β and overexpression of p‐NR1 may participate in this process. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a common adverse reaction of the anticancer drug. Among these chemotherapeutic agents, cisplatin, an effective chemotherapeutic drug, is extensively applied to the treatment of solid tumours, yet various adverse reactions, especially AKI, often limit their use. However, the pathogenesis of AKI caused by cisplatin remains poorly clarified. Therefore, we tested whether microRNAs, which have been certified as key regulators of disease are involved in this process. AKI mouse and HK2 cells were treated with cisplatin. Annexin V/PI staining and cleaved caspase‐3 were used to assess apoptosis. Western blot analyses and qRT‐PCR were used to evaluate the protein and mRNA level of TRPC6 and DRP1. miR‐26a was remarkably decreased in cisplatin‐induced AKI and in cisplatin co‐cultured HK2 cells. Furthermore, we used a miR‐26a mimics in vitro and found that apoptosis was alleviated than that in the control cells. We further verified that miR‐26a protected against cisplatin‐induced cell apoptosis by acting on transient receptor potential channel 6 (TRPC6) which can regulate the expression of dynamin‐related protein 1 (DRP1), thus inhibited the mitochondrial apoptosis pathway. Therefore, the study unveiled that miR‐26a/TRPC6/DRP1 is a novel protective pathway in cisplatin‐induced AKI and may be targeted for the prevention and treatment of drug‐related renal injury. Significance of the Study: Our study found that miR‐26a was significantly downregulated during cisplatin‐induced AKI and during cisplatin co‐cultured HK2 cells. Further, in vitro we used miR‐26a mimic to intervene cells and found that apoptosis alleviated compared with control group. We further verified that miR‐26a protected cisplatin‐induced apoptosis by target transient receptor potential channel 6 (TRPC6) which can regulate the expression of dynamic‐related protein 1 (DRP1) and inhibit the mitochondrial apoptosis pathway. Thus, miR‐26a/TRPC6/DRP1 is a new protective pathway in cisplatin‐induced AKI and may be targeted for the prevention and treatment of drug‐related acute kidney injury. [ABSTRACT FROM AUTHOR]

A new protocol for SO bond formation was developed by electrochemical oxidative cross‐coupling between alcohols and thiophenols. With this strategy, a series of valuable sulfinic ester derivatives were synthesized up to 96% yield from basic starting materials. A preliminary mechanistic investigation reveals that this reaction involves oxygen reduction reaction (ORR). [ABSTRACT FROM AUTHOR]

The discovery of hypoxia-inducible factor (HIF)-prolyl hydroxylase inhibitor (PHI) has revolutionized the treatment strategy for renal anemia. However, the presence of multiple transcription targets of HIF raises safety concerns regarding HIF-PHI. Here, we explored the dose-dependent effect of MK-8617 (MK), a kind of HIF-PHI, on renal fibrosis. MK was administered by oral gavage to mice for 12 wk at doses of 1.5, 5, and 12.5 mg/kg. In vitro, the human proximal tubule epithelial cell line HK-2 was treated with increasing doses of MK administration. Transcriptome profiling was performed, and fibrogenesis was evaluated. The dose-dependent biphasic effects of MK on tubulointerstitial fibrosis (TIF) were observed in chronic kidney disease mice. Accordingly, high-dose MK treatment could significantly enhance TIF. Using RNA-sequencing, combined with in vivo and in vitro experiments, we found that Krüppel-like factor 5 (KLF5) expression level was significantly increased in the proximal tubular cells, which could be transcriptionally regulated by HIF-1α with high-dose MK treatment but not low-dose MK. Furthermore, our study clarified that HIF-1α-KLF5-TGF-β1 signaling activation is the potential mechanism of high-dose MK-induced TIF, as knockdown of KLF5 reduced TIF in vivo. Collectively, our study demonstrates that high-dose MK treatment initiates TIF by activating HIF-1α-KLF5-TGF-β1 signaling. These findings provide novel insights into TIF induction by high-dose MK (HIF-PHI), suggesting that the safety dosage window needs to be emphasized in future clinical applications. [ABSTRACT FROM AUTHOR]

A novel AgCl/AgIO4 composite was fabricated via an in-suit synthetic method. The as-prepared samples have been characterised by using X-ray diffraction, transmission electron microscopy, scanning electron microscopy, UV-vis diffuse reflectance spectroscopy, X-ray photoelectron spectroscopy and electrochemical impedance spectroscopy. Rhodamine B dilute solution was used to discuss the photocatalytic activities of the as-prepared composites under the visible light irradiation. Experimental results showed that with increasing the contents of AgIO4 the photocatalytic activity of the as-prepared hybrids was first increased and then decreased. When the molar ratio of AgCl to AgIO4 was 1:5, in 30 min, the as-prepared composites with the bandgap of 1.21 eV exhibited the highest photocatalytic activity and possessed 96.3% of degradation efficiency. That was increased by 71.5 and 27.9% compared with AgCl and AgIO4, respectively. Moreover, AgCl was linked with AgIO4 via chemical bonds rather than physical contact at the interfaces of these two semiconductors. In addition, a possible photocatalytic degradation mechanism for the as-prepared hybrids was also presented. [ABSTRACT FROM AUTHOR]

The novel AgCl/Ag2SO3 hybrids as an efficient photocatalyst had been fabricated by an in situ synthetic method. The correlations between the structure and the photocatalytic properties of the as‐fabricated hybrids were analyzed. Experimental results exhibited that with increasing the amount of Ag2SO3, the degradation rate of the as‐obtained samples was firstly increased and then decreased under the visible light irradiation. When the mass ratio of AgCl to Ag2SO3 was 1:2, in 30 min, it displayed the highest degradation rate of 99.2% for rhodamine‐B, which was obviously higher than 46.1, 60.5, and 14.6% of pure AgCl, Ag2SO3, and TiO2 (P25), respectively. Similar results could be found in degradation of methyl orange. It had the maximum of 97.4% in 90 min, which was higher than 55.2, 48.7, and 12.7% of pure AgCl, Ag2SO3, and P25, respectively. Moreover, the as‐prepared hybrids possessed the enhanced separation and transfer of photo‐generated electron–hole pairs compared to the pure samples. In addition, the holes and superoxide radicals played the dominant role and the hydroxyl radicals played the secondary role during the process of photocatalytic degradation. [ABSTRACT FROM AUTHOR]

Abstract: Extracellular vesicles (EVs) are nanosized, membrane‐bound vesicles released from different cells. Recent studies have revealed that EVs may participate in renal tissue damage and regeneration through mediating inter‐nephron communication. Thus, the potential use of EVs as therapeutic vector has gained considerable interest. In this review, we will discuss the basic characteristics of EVs and its role in nephron cellular communication. Then, the application of EVs as therapeutic vector based on its natural content or as carriers of drug, in acute and chronic kidney injury, was discussed. Finally, perspectives and challenges of EVs in therapy of kidney disease were described. [ABSTRACT FROM AUTHOR]

The effects of elevated CO2 concentration on the growth and development of the funnel-web weaving spider Agelena labyrinthica ( Clerck) ( Araneae: Agelenidae) were studied in climate chambers with low (370 μl l−1) or high (750 μl l−1) CO2 concentration. Seventh-instar A. labyrinthica cultured under each of these CO2 concentrations were randomly selected to determine nutrient composition (total protein, total amino acid, and free fatty acid) and digestive or detoxification enzymes activity (peroxidase, amylase, and superoxide dismutase) using test kits. When reared under high CO2 concentration, total development of A. labyrinthica was significantly faster. Carapace length and width and body weight did not differ between CO2 concentrations, nor the levels of protein and total amino acids in seventh-instar A. labyrinthica. However, free fatty acid levels were significantly lower under high CO2 concentration. Specific activities of peroxidase and superoxide dismutase in seventh-instar A. labyrinthica did not differ between CO2 concentrations. The specific activity of amylase under high CO2 concentration was higher than that of the low CO2 group. The effects of elevated CO2 on A. labyrinthica varied from those on the wandering spider Pardosa astrigera L Koch, as found in an earlier study. Apparently, elevated CO2 has a species-specific impact on spiders. [ABSTRACT FROM AUTHOR]

A methodology based on the support vector machine (SVM) combined with a hybrid kernel function (HKF) for accurately modeling the resonant frequencies of the compact microstrip antenna (MSA) is presented and dedicated to reduce the number of samples and simplify the structure when predicting the resonant frequency of the compact MSA by artificial neural network. The parameters of the SVMs and weight coefficients of the HKF are optimized by means of particle swarm optimization algorithm. In addition, two different kernel functions (KFs), namely polynomial KF (a kind of global KF) and Cauchy KF (a kind of local KF), are employed to overcome the disadvantages of traditional KF. The proposed method is validated by the UCI database. The evaluation results show that the HKF can improve the learning ability and generalization ability of the SVM. Furthermore, the resonant frequencies of a planar inverted F-shaped antenna and an L-shaped MSA are modeled by the proposed method. Predictive results with high accuracy demonstrate that the particle swarm optimization-based SVM with the HKF can improve the prediction accuracy for a small dataset. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Two new triterpenoid glycosides, 3 α,19 α,23 α-trihydroxy-2-oxo-12-ursen-28- O- β- d-glucopyranoside ( 1) and 3 α,19 α,23 α-trihydroxy-2-oxoolean-12-en-28- O- β- d-glucopyranoside ( 2) as well as three known compounds, 2 α,3 α,19 α-trihydroxyolean-12-en-28- O- β- d-glucopyranoside ( 3), 2 α,3 α,19 α,23-tetrahydroxy-12-ursen-28- O- β- d-glucopyranoside ( 4), and 2 α,3 β,19 α,23-tetrahydroxyurs-12-en-28-oic acid ( 5) were isolated from 75% Et OH extract of Rosa cymosa. Their structures were elucidated by extensive spectroscopic methods. All the isolated compounds displayed moderate inhibitory activity against LPS-induced NO production in macrophages. [ABSTRACT FROM AUTHOR]

Cyclophilin A (Cyp A), a member of the peptidyl-prolyl isomerase (PPI) family, may function as a molecular signalling switch. Comparative proteomic studies have identified Cyp A as a potential downstream target of protein kinase B (Akt). This study confirmed that Cyp A is a downstream effector of the phosphatidylinositide 3-kinase (PI3K)/Akt signalling pathway. Cyp A was highly phosphorylated in response to interleukin-6 treatment, which was consistent with the accumulation of phosphorylated Akt, suggesting that Cyp A is a phosphorylation target of Akt and downstream effector of the PI3K/Akt pathway. Cyclosporine A (CsA), a PPI inhibitor, inhibited the growth of multiple myeloma (MM) U266 cells. Moreover, CsA treatment inhibited the activation of the signal transducer and activator of transcription 3 (STAT3) in MM U266 cells. Several Cyp A mutants were generated. Mutants with mutated AKT phosphorylation sites increased the G1 phase arrest in MM U266 cells. The other mutants that mimicked the phosphorylated state of Cyp A decreased the percentage of G1 phase. These results demonstrated that the states of phosphorylation of Cyp A by Akt can influence the progress of the cell cycle in MM U266 cells and that this effect is probably mediated through the Janus-activated kinase 2/STAT3 signalling pathway. [ABSTRACT FROM AUTHOR]

We have developed a method for recyclable hypervalent-iodine-mediated direct dehydrogenative α,β′- bifunctionalization of β-ketoesters and β-diketones under metal-free conditions, which affords a straightforward way to synthesize benzo-fused 2,3-dihydrofurans. This efficient, mild method, which has a wide substrate scope and good functional-group tolerance, was used for the multistep synthesis of the protected aglycone of a naturally occurring phenolic glycoside. A mechanism involving Michael addition to an enone intermediate and subsequent oxidative cyclization is proposed. [ABSTRACT FROM AUTHOR]

Geologic disposal of supercritical CO2 in saline aquifers and depleted oil and gas fields will cause large volumes of brine to become saturated with dissolved CO2 at concentrations of 40 g/l or more. As CO2 dissolves in brine, the brine density increases slightly. This property favors the long-term storage security of the CO2 because the denser brine is less likely to move upwards toward shallower depths. However, there are plausible mechanisms by which the CO2-laden brine could be transported to a shallower depth, where the CO2 would come out of solution (exsolve), forming a mobile CO2 gas phase. Recent laboratory experiments of the exsolution process show that the CO2 phase relative permeability measured during exsolution is on the order of 1000 times lower than the relative permeability measured during a conventional CO2 core flood. Numerical simulations of upward brine migration through an open fault were performed using TOUGH2-ECO2N with the two types of relative permeability functions. When traditional core flood relative permeabilities are used, upward flow of a CO2 saturated brine leads to exsolution and the development of a highly mobile CO2 gas phase. When relative permeabilities measured during exsolution are used, the tendency for the exsolved CO2 to migrate as a separate phase is greatly reduced, and the exsolved CO2 can partially block brine flow through the open fault. For the conditions considered, use of the exsolution relative permeability functions reduced the upward CO2 flux by about a factor of four compared to the case with core flood relative permeability functions. © 2013 Society of Chemical Industry and John Wiley & Sons, Ltd [ABSTRACT FROM AUTHOR]

Increased vascular resistance in the fetoplacental circulation is a characteristic of preeclampsia. However, the potential molecular mechanisms of this condition remain obscure. The current study aimed to determine the direct effect of the peptide antigen corresponding to the second extracellular loop of the angiotensin II type 1 receptor (AT1R-ECII) activating autoantibody (AT1-AA), a novel risk factor in preeclamptic patients, on fetoplacental villus stem blood vessels. Immunohistochemistry revealed that AT1 receptors were localized in the veins and arteries of human placental villi. Among 58 serum samples from preeclamptic patients, 28 (48.28%) were proved AT1-AA-positive by enzyme-linked immunosorbent assay [ P < 0.01 vs. 2/51 (3.92%) in the normal pregnancy group]. Total IgGs purified from AT1-AA-positive patients' sera (AT1-AA-IgGs) were added to isolated normal human placental blood vessels. The IgG significantly constricted both the villus veins and arteries in a dose-dependent manner in vitro, which could be blocked by the peptide corresponding to the human AT1R-ECII, anti-human IgG or the AT1 receptor antagonist losartan. Additionally, the venous constriction induced by AT1-AA-IgGs remained unchanged even at the end of the experiment (about half an hour), but the vasoconstriction caused by the AT1 receptor agonist angiotensin II underwent desensitization within three minutes. Collectively, our results demonstrated that AT1-AA in preeclamptic sera can directly constrict fetoplacental villus blood vessels without desensitization via the AT1 receptor in vitro, which might contribute to poor fetoplacental perfusion in preeclampsia. J. Cell. Physiol. 228: 142-148, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]