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10.1038/srep33678 http://scihub22266oqcxt.onion/10.1038/srep33678 C5030486!5030486 !27649628     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\27649628 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Sci+Rep 2016 ; 6 (ä): 33678 Nephropedia Template TP {{tp|p=27649628 |t=2016. Neprilysin is a Mediator of Alternative Renin-Angiotensin-System Activation in the Murine and Human Kidney |pdf=|usr=}}{{27649628 }} gab.com Text Neprilysin is a Mediator of Alternative Renin-Angiotensin-System Activation in the Murine and Human Kidney JO: Sci Rep http://www.kidney.de/pget.php?&tw=1&pmid=27649628 #FOAvip Cardiovascular and renal pathologies are frequently associated with an activated renin-angiotensin-system (RAS) and increased levels of its main effector and vasoconstrictor hormone angiotensin II (Ang II). Angiotensin-converting-enzyme-2 (ACE2) has been described as a crucial enzymatic player in shifting the RAS towards its so-called alternative vasodilative and reno-protective axis by enzymatically converting Ang II to angiotensin-(1-7) (Ang-(1-7)). Yet, the relative contribution of ACE2 to Ang-(1-7) formation in vivo has not been elucidated. Mass spectrometry based quantification of angiotensin metabolites in the kidney and plasma of ACE2 KO mice surprisingly revealed an increase in Ang-(1-7), suggesting additional pathways to be responsible for alternative RAS activation in vivo. Following assessment of angiotensin metabolism in kidney homogenates, we identified neprilysin (NEP) to be a major source of renal Ang-(1-7) in mice and humans. These findings were supported by MALDI imaging, showing NEP mediated Ang-(1-7) formation in whole kidney cryo-sections in mice. Finally, pharmacologic inhibition of NEP resulted in strongly decreased Ang-(1-7) levels in murine kidneys. This unexpected new role of NEP may have implications for the combination therapy with NEP-inhibitors and angiotensin-receptor-blockade, which has been shown being a promising therapeutic approach for heart failure therapy. Twit Text FOAVip Neprilysin is a Mediator of Alternative Renin-Angiotensin-System Activation in the Murine and Human Kidney ????Sci Rep http://www.kidney.de/pget.php?&tw=1&pmid=27649628 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27649628 #FOAvip English Wikipedia <ref>{{Cite pmid|27649628 }}</ref> Neprilysin is a Mediator of Alternative Renin-Angiotensin-System Activation in the Murine and Human Kidney #MMPMID27649628 Domenig O ; Manzel A ; Grobe N ; Königshausen E ; Kaltenecker CC ; Kovarik JJ ; Stegbauer J ; Gurley SB ; van Oyen D ; Antlanger M ; Bader M ; Motta-Santos D ; Santos RA ; Elased KM ; Säemann MD ; Linker RA ; Poglitsch M Sci Rep 2016[Sep]; 6 (ä): 33678 PMID27649628 show ga Cardiovascular and renal pathologies are frequently associated with an activated renin-angiotensin-system (RAS) and increased levels of its main effector and vasoconstrictor hormone angiotensin II (Ang II). Angiotensin-converting-enzyme-2 (ACE2) has been described as a crucial enzymatic player in shifting the RAS towards its so-called alternative vasodilative and reno-protective axis by enzymatically converting Ang II to angiotensin-(1-7) (Ang-(1-7)). Yet, the relative contribution of ACE2 to Ang-(1-7) formation in vivo has not been elucidated. Mass spectrometry based quantification of angiotensin metabolites in the kidney and plasma of ACE2 KO mice surprisingly revealed an increase in Ang-(1-7), suggesting additional pathways to be responsible for alternative RAS activation in vivo. Following assessment of angiotensin metabolism in kidney homogenates, we identified neprilysin (NEP) to be a major source of renal Ang-(1-7) in mice and humans. These findings were supported by MALDI imaging, showing NEP mediated Ang-(1-7) formation in whole kidney cryo-sections in mice. Finally, pharmacologic inhibition of NEP resulted in strongly decreased Ang-(1-7) levels in murine kidneys. This unexpected new role of NEP may have implications for the combination therapy with NEP-inhibitors and angiotensin-receptor-blockade, which has been shown being a promising therapeutic approach for heart failure therapy. |Aminobutyrates/pharmacology [MESH] |Angiotensin I/metabolism [MESH] |Angiotensin II/genetics/metabolism [MESH] |Angiotensin-Converting Enzyme 2 [MESH] |Animals [MESH] |Biomarkers [MESH] |Biopsy [MESH] |Biphenyl Compounds/pharmacology [MESH] |Female [MESH] |Gene Expression [MESH] |Humans [MESH] |Immunohistochemistry [MESH] |Kidney Cortex/physiology [MESH] |Kidney/*physiology [MESH] |Mice [MESH] |Mice, Knockout [MESH] |Neprilysin/antagonists & inhibitors/*metabolism [MESH] |Peptide Fragments/metabolism [MESH] |Peptidyl-Dipeptidase A/genetics/metabolism [MESH] |Renin-Angiotensin System/*physiology [MESH]Neprilysin is a Mediator of Alternative Renin-Angiotensin-System Activ(epmc).pdf DeepDyve Pubget Overpricing