Use my Search Websuite to scan PubMed, PMCentral, Journal Hosts and Journal Archives, FullText. Kick-your-searchterm to multiple Engines kick-your-query now !>

A dictionary by aggregated review articles of nephrology, medicine and the life sciences Your one-stop-run pathway from word to the immediate pdf of peer-reviewed on-topic knowledge.

10.1371/journal.pone.0003742 http://scihub22266oqcxt.onion/10.1371/journal.pone.0003742 19011682!2580028!19011682     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       PLoS+One 2008 ; 3 (11): e3742 Nephropedia Template TP {{tp|p=19011682|t=2008. Potential relevance of alpha(1)-adrenergic receptor autoantibodies in refractory hypertension |pdf=|usr=}}{{19011682}} gab.com Text Potential relevance of alpha(1)-adrenergic receptor autoantibodies in refractory hypertension JO: PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=19011682 #FOAvip BACKGROUND: Agonistic autoantibodies directed at the alpha(1)-adrenergic receptor (alpha(1)-AAB) have been described in patients with hypertension. We implied earlier that alpha(1)-AAB might have a mechanistic role and could represent a therapeutic target. METHODOLOGY/PRINCIPAL FINDINGS: To pursue the issue, we performed clinical and basic studies. We observed that 41 of 81 patients with refractory hypertension had alpha(1)-AAB; after immunoadsorption blood pressure was significantly reduced in these patients. Rabbits were immunized to generate alpha(1)-adrenergic receptor antibodies (alpha(1)-AB). Patient alpha(1)-AAB and rabbit alpha(1)-AB were purified using affinity chromatography and characterized both by epitope mapping and surface plasmon resonance measurements. Neonatal rat cardiomyocytes, rat vascular smooth muscle cells (VSMC), and Chinese hamster ovary cells transfected with the human alpha(1A)-adrenergic receptor were incubated with patient alpha(1)-AAB and rabbit alpha(1)-AB and the activation of signal transduction pathways was investigated by Western blot, confocal laser scanning microscopy, and gene expression. We found that phospholipase A2 group IIA (PLA2-IIA) and L-type calcium channel (Cacna1c) genes were upregulated in cardiomyocytes and VSMC after stimulation with both purified antibodies. We showed that patient alpha(1)-AAB and rabbit alpha(1)-AB result in protein kinase C alpha activation and transient extracellular-related kinase (EKR1/2) phosphorylation. Finally, we showed that the antibodies exert acute effects on intracellular Ca(2+) in cardiomyocytes and induce mesentery artery segment contraction. CONCLUSIONS/SIGNIFICANCE: Patient alpha(1)-AAB and rabbit alpha(1)-AB can induce signaling pathways important for hypertension and cardiac remodeling. Our data provide evidence for a potential clinical relevance for alpha(1)-AAB in hypertensive patients, and the notion of immunity as a possible cause of hypertension. Twit Text FOAVip Potential relevance of alpha(1)-adrenergic receptor autoantibodies in refractory hypertension ????PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=19011682 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=19011682 #FOAvip English Wikipedia <ref>{{Cite pmid|19011682}}</ref> Potential relevance of alpha(1)-adrenergic receptor autoantibodies in refractory hypertension #MMPMID19011682 Wenzel K; Haase H; Wallukat G; Derer W; Bartel S; Homuth V; Herse F; Hubner N; Schulz H; Janczikowski M; Lindschau C; Schroeder C; Verlohren S; Morano I; Muller DN; Luft FC; Dietz R; Dechend R; Karczewski P PLoS One 2008[]; 3 (11): e3742 PMID19011682show ga BACKGROUND: Agonistic autoantibodies directed at the alpha(1)-adrenergic receptor (alpha(1)-AAB) have been described in patients with hypertension. We implied earlier that alpha(1)-AAB might have a mechanistic role and could represent a therapeutic target. METHODOLOGY/PRINCIPAL FINDINGS: To pursue the issue, we performed clinical and basic studies. We observed that 41 of 81 patients with refractory hypertension had alpha(1)-AAB; after immunoadsorption blood pressure was significantly reduced in these patients. Rabbits were immunized to generate alpha(1)-adrenergic receptor antibodies (alpha(1)-AB). Patient alpha(1)-AAB and rabbit alpha(1)-AB were purified using affinity chromatography and characterized both by epitope mapping and surface plasmon resonance measurements. Neonatal rat cardiomyocytes, rat vascular smooth muscle cells (VSMC), and Chinese hamster ovary cells transfected with the human alpha(1A)-adrenergic receptor were incubated with patient alpha(1)-AAB and rabbit alpha(1)-AB and the activation of signal transduction pathways was investigated by Western blot, confocal laser scanning microscopy, and gene expression. We found that phospholipase A2 group IIA (PLA2-IIA) and L-type calcium channel (Cacna1c) genes were upregulated in cardiomyocytes and VSMC after stimulation with both purified antibodies. We showed that patient alpha(1)-AAB and rabbit alpha(1)-AB result in protein kinase C alpha activation and transient extracellular-related kinase (EKR1/2) phosphorylation. Finally, we showed that the antibodies exert acute effects on intracellular Ca(2+) in cardiomyocytes and induce mesentery artery segment contraction. CONCLUSIONS/SIGNIFICANCE: Patient alpha(1)-AAB and rabbit alpha(1)-AB can induce signaling pathways important for hypertension and cardiac remodeling. Our data provide evidence for a potential clinical relevance for alpha(1)-AAB in hypertensive patients, and the notion of immunity as a possible cause of hypertension. |Adsorption/drug effects[MESH] |Aged[MESH] |Aged, 80 and over[MESH] |Animals[MESH] |Autoantibodies/*immunology/isolation & purification/pharmacology[MESH] |Blood Pressure/drug effects[MESH] |Calcium Channels, L-Type/metabolism[MESH] |Calcium/metabolism[MESH] |Enzyme Activation/drug effects[MESH] |Epitope Mapping[MESH] |Extracellular Signal-Regulated MAP Kinases/metabolism[MESH] |Female[MESH] |Humans[MESH] |Hypertension/*immunology/physiopathology[MESH] |Intracellular Space/drug effects/metabolism[MESH] |Male[MESH] |Middle Aged[MESH] |Muscle, Smooth, Vascular/cytology[MESH] |Myocytes, Cardiac/drug effects/enzymology[MESH] |Myocytes, Smooth Muscle/drug effects/enzymology[MESH] |Phospholipases A2/metabolism[MESH] |Protein Kinase C/metabolism[MESH] |Protein Structure, Secondary[MESH] |Rats[MESH]Potential relevance of alpha(1)-adrenergic receptor autoantibodies in (epmc).pdf DeepDyve Pubget Overpricing