A PHP Error was encountered

Severity: Warning

Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests

Filename: helpers/my_audit_helper.php

Line Number: 143

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3098
Function: getPubMedXML

File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global

File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Attempt to read property "Count" on bool

Filename: helpers/my_audit_helper.php

Line Number: 3100

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3100
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global

File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword

File: /var/www/html/index.php
Line: 316
Function: require_once

Sacubitril/Valsartan Improves Left Ventricular Function in Chronic Pressure Overload Independent of Intact Cyclic Guanosine Monophosphate-dependent Protein Kinase I Alpha Signaling. | LitMetric

AI Article Synopsis

  • Sacubitril/valsartan (Sac/Val) is a treatment for heart failure that works by preventing the breakdown of natriuretic peptides, potentially enhancing cGMP-PKG signaling.
  • Researchers studied the impact of Sac/Val on mice with a specific mutation affecting PKG to see if it was necessary for the drug's effectiveness.
  • Despite the mutation, Sac/Val still improved heart structure and function in mice, indicating that other signaling pathways aside from the natriuretic peptide-cGMP-PKG pathway may also contribute to its benefits in heart failure.

Article Abstract

Background: Combined angiotensin receptor/neprilysin inhibition with sacubitril/valsartan (Sac/Val) has emerged as a therapy for heart failure. The presumed mechanism of benefit is through prevention of natriuretic peptide degradation, leading to increased cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) signaling. However, the specific requirement of PKG for Sac/Val effects remains untested.

Methods And Results: We examined Sac/Val treatment in mice with mutation of the cGMP-dependent protein kinase I (PKGI)α leucine zipper domain, which is required for cGMP-PKGIα antiremodeling actions in vivo. Wild-type (WT) or PKG leucine zipper mutant (LZM) mice were exposed to 56-day left ventricular (LV) pressure overload by moderate (26G) transaortic constriction (TAC). At day 14 after TAC, mice were randomized to vehicle or Sac/Val by oral gavage. TAC induced the same degree of LV pressure overload in WT and LZM mice, which was not affected by Sac/Val. Although LZM mice, but not WT, developed LV dilation after TAC, Sac/Val improved cardiac hypertrophy and LV fractional shortening to the same degree in both the WT and LZM TAC mice.

Conclusion: These findings indicate the beneficial effects of Sac/Val on LV structure and function in moderate pressure overload. The unexpected finding that PKGIα mutation does not abolish the Sac/Val effects on cardiac hypertrophy and on LV function suggests that signaling other than natriuretic peptide- cGMP-PKG mediates the therapeutic benefits of neprilysin inhibition in heart failure.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529795PMC
http://dx.doi.org/10.1016/j.cardfail.2020.04.011DOI Listing

Publication Analysis

Top Keywords

pressure overload
16
protein kinase
12
lzm mice
12
left ventricular
8
cyclic guanosine
8
sac/val
8
heart failure
8
cgmp-dependent protein
8
sac/val effects
8
leucine zipper
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!