Publication Detail

Citation : Buckley CL, Stokes AJ. (2011)
Corin-deficient W-sh mice poorly tolerate increased cardiac afterload.
Regul Pept 172(1-3):44-50.
Abstract : C57BL/6-Kit(W-sh/W-sh) mice are generally regarded as a mast cell-deficient model, as they lack the necessary kit receptor for mast cell development. Further characterization of this strain, however, indicates that C57BL/6-Kit(W-sh/W-sh) mice also have a disruption in the Corin gene. Corin is a transmembrane serine protease critical for processing atrial natriuretic peptide (ANP) from pro-ANP through proteolytic cleavage. Pro-ANP is produced, stored and released by cardiac myocytes in response to atrial stretch and the stress generated by increased afterload such as increased ventricular pressure from aortic stenosis or myocardial infarction. ANP inhibits the effects of the renin-angiotensin system to preserve homeostasis under conditions of increased hemodynamic load, and changes in the level of its activating enzyme Corin have been observed during the progression to heart failure. Here, we investigate the effect of increased hemodynamic load on Corin-deficient C57BL/6-Kit(W-sh/W-sh) mice. Ten-week old male mice were subjected to transverse aortic constriction for 8 weeks and were monitored for changes in cardiac structure and function by echocardiography. Hearts were collected 8 weeks after surgery for molecular and histological analyses. Corin-deficient C57BL/6-Kit(W-sh/W-sh) mice developed rapidly progressive and substantial left ventricular dilation, hypertrophy, and markedly impaired cardiac function during the 8 weeks after surgery, compared to wildtype mice. Concomitant with this we observed increased levels of ANP transcript, but a lack of prepro-ANP or pro-ANP protein in heart tissue extracted from Corin-deficient mice. Surprisingly, fibrosis was not increased in Corin-deficient mice when compared to wildtype mice. These data indicate that Corin's involvement in ANP processing is a key element in the heart's response to increased hemodynamic load. Further, C57BL/6-Kit(W-sh/W-sh) strain is an effective model for investigating the involvement of Corin and, conversely, a less than optimal model for investigating mast cell, and immunological, functions in certain cardiovascular pathologies.
URL Link : http://www.ncbi.nlm.nih.gov/pubmed/21903139
PMID : 21903139
PMCID : PMC3196309
News
23 July 2018:
2018 Health Disparities Research Institute

Apply Now to the 2018 Health Disparities Research Institute!

The National Institute on Minority Health and Health Disparities (NIMHD) will host the…

12 July 2018:
Summer Career Development Workshop July 12-13, Seattle WA

Geographic Management of Cancer Health Disparities (GMap)
Summer Career Development Workshop July 12-13, Seattle WA

We want to hear from you! If h…

05 April 2018:
Meharry Medical College will host a Grant Writing Workshop on April 5-6, 2018

Meharry Translational Research Center (MeTRC), in conjunction with Office of Minority Health Resource Center (OMHRC), will host a Grant Writing Worksh…


View more news...


Seminars & Events
18 April 2018, 8am:
ANNUAL BIOMEDICAL SCIENCES and HEALTH DISPARITIES SYMPOSIUM
02 April 2018, 12pm - 2pm:
HEALTH SCIENCES INTERDISCIPLINARY POSTER FESTIVAL
16 March 2018, 5pm:
ANNUAL BIOMEDICAL SCIENCES and HEALTH DISPARITIES SYMPOSIUM - Abstract Deadline

View more seminars & events...

Supported by a grant from the National Institute on Minority Health and Health Disparities (U54MD007584), National Institutes of Health.