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1.
Abundant evidence documents the highly proinflammatory actions of lysophosphatidylcholine (LPC). Further, LPC, found in high amounts in oxidized low-density lipoprotein (LDL), is implicated as an atherogenic factor. In endothelial cells, LPC impairs endothelial barrier function through GPR4, a novel receptor hypothesized to be sensitive to LPC and protons. The authors investigated the stimulation by LPC or low pH of GPR4 in human brain microvascular endothelial cells (HBMECs) and whether the activated GPR4 regulates in vitro monocyte transmigration. The results indicated that HBMECs stimulated by LPC (5 microM), but not low pH, showed a twofold increase in monocyte transmigration. Using retroviruses containing siRNA to GPR4, a > 60% reduction of GPR4 expression resulted in blockade of the LPC-stimulated transmigration. The inhibited response was restored by co-expression with an small interference RNA (siRNA)-resistant, but functional, GPR4 mutant construct. To investigate potential signaling mechanisms, the siRNA-mediated knockdown of GPR4 also prevented LPC-induced RhoA activation. C3 transferase, a Rho inhibitor, prevented approximately approximately 65% of the LPC-stimulated transmigration. LPC also increased MLC phosphorylation by 5 min, which was inhibited by the Rho kinase inhibitor, Y-27632 (10 microM) or ML-7 (myosin light chain kinase (MLCK) inhibitor). The findings indicate that the proinflammatory and atherogenic LPC stimulated endothelial GPR4, which promoted monocyte transmigration through a RhoA-dependent pathway. 相似文献
2.
Transcytosis in the continuous endothelium of the myocardial microvasculature is inhibited by N-ethylmaleimide. 总被引:3,自引:0,他引:3
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D Predescu R Horvat S Predescu G E Palade 《Proceedings of the National Academy of Sciences of the United States of America》1994,91(8):3014-3018
In a murine heart perfusion system, we were able to "turn off" the transport of derivatized albumin [dinitrophenylated albumin (DNP-albumin)] from the perfusate to the tissue, by preperfusing the system with 1 mM N-ethylmaleimide (NEM) for 5 min at 37 degrees C, followed by a 5-min perfusion of DNP-albumin in the presence of NEM. Using a postembedding immunocytochemical procedure, we showed that (i) a 30-sec to 1-min treatment of heart vasculature with 1 mM NEM reduces the transendothelial transport of DNP-albumin and nearly stops it after 5 min, and (ii) DNP-albumin is detected exclusively in plasmalemmal vesicles (PVs) while in transit across endothelial cells. Perfusion with 10 mM dithiothreitol for 1 min before NEM prevents the inhibition of vesicular transport. To quantitate the NEM effect on vesicular transport inhibition, we developed an ELISA and a dot-blot assay for measuring DNP-albumin in supernatants of perfused whole-heart homogenates. The results obtained indicate that the treatment of the heart vasculature with 1 mM NEM decreases the vesicular transport of DNP-albumin by 78-80%. Since NEM is known to inhibit the fusion of different types of vesicular carriers with their target membranes in other cell types and in in vitro reconstituted cellular systems, by alkylating a NEM-sensitive factor, we assume that the same mechanism applies in our in situ system. The decrease of vesicular transport can be explained by NEM preventing the fusion of recycling vesicles with their targets--i.e., the abluminal and luminal domains of the plasmalemma. The results open to question previous interpretations from other laboratories according to which plasmalemmal vesicles are sessile, immobile structures. 相似文献
3.
Bratu Ovidiu Dragos R. Marcu Dan L. D. Mischianu Catalina Poiana Camelia C. Diaconu Simona G. Bungau Delia M. Tit Alin Cumpanas Roxana Bohiltea 《Archives of Medical Science》2022,18(4):881
Androgen insensitivity syndrome (AIS) is an X-linked recessive genetic syndrome that occurs as result of an androgen receptor mutation; it affects the normal masculinization process in chromosomal male patients. More than 900 androgen receptor mutations that can lead to AIS have been identified. The complete androgen insensitivity is characterized by a total lack of response to androgens, usually in patients with 46XY karyotype but with feminine phenotype. Primary amenorrhoea and inguinal swellings in female patients are the main signs that could raise suspicion for this syndrome. Patients with partial androgen insensitivity have ambiguous genitalia at birth and gynecomastia during puberty, whereas those with mild androgen insensitivity present a normal male phenotype but altered spermatogenesis during adulthood and pubertal gynecomastia. The diagnosis of AIS often proves to be a challenge; its management is complex and requires a multidisciplinary approach to meet decision-making challenges in sex assignment, fertility and timing of gonadectomy, psychological outcomes and genetic counselling. 相似文献
4.
Pohoey Fan M.D. Roxana C. Sisu M.D. Dragos Vinereanu M.D. Ph.D. F.E.S.C. 《Echocardiography (Mount Kisco, N.Y.)》2011,28(4):475-475
Article Title: Different Mechanisms for Diastolic Mitral Regurgitation Illustrated by Three Comparative Cases(Echocardiography 2011;28:475) 相似文献
5.
Khan Khurrum Kim Jitae A. Gurgu Andra Khawaja Muzamil Cozma Dragos Chelu Mihail G. 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》2022,36(4):763-775
Cardiovascular Drugs and Therapy - Cardiac implantable electronic devices (CIEDs) are essential for the management of a variety of cardiac conditions, including tachyarrhythmias, bradyarrhythmias,... 相似文献
6.
7.
Trasca Livia Sanchis Laura Regueiro Ander Freixa Xavier Vinereanu Dragos Sitges Marta 《The international journal of cardiovascular imaging》2021,37(5):1577-1585
The International Journal of Cardiovascular Imaging - The aim of our study was to assess the anatomical changes of the mitral valve apparatus after percutaneous repair with the MitraClip®... 相似文献
8.
Gonadotropes are crucial in the control of reproduction but difficult to isolate for functional analysis due to their scattered distribution in the anterior pituitary gland. We devised a binary genetic approach, and describe a new mouse model that allows visualization and manipulation of gonadotrope cells. Using gene targeting in embryonic stem cells, we generated mice in which Cre recombinase is coexpressed with the GnRH receptor, which is expressed in gonadotrope cells. We show that we can direct Cre-mediated recombination of a yellow fluorescent protein reporter allele specifically in gonadotropes within the anterior pituitary of these knock-in mice. More than 99% of gonadotropin-containing cells were labeled by yellow fluorescent protein fluorescence and readily identifiable in dissociated pituitary cell culture, allowing potentially unbiased sampling from the gonadotrope population. Using electrophysiology, calcium imaging, and the study of secretion on the single-cell level, the functional properties of gonadotropes isolated from male mice were analyzed. Our studies demonstrate a significant heterogeneity in the resting properties of gonadotropes and their responses to GnRH. About 50% of gonadotropes do not exhibit secretion of LH or FSH. Application of GnRH induced a broad range of both electrophysiological responses and increases in the intracellular calcium concentration. Our mouse model will also be able to direct expression of other Cre recombination-dependent reporter genes to gonadotropes and, therefore, represents a versatile new tool in the understanding of gonadotrope biology. 相似文献
9.
10.
Cristian Mornos Lucian Petrescu Dragos Cozma Adina Ionac 《Arquivos brasileiros de cardiologia》2014,102(1):19-29