Corin

Armaly, Zaher; Assady, Suheir; Abassi, Zaid

doi:10.1097/01.mnh.0000435609.35789.32

Cited by 43 publications

(21 citation statements)

References 77 publications

(101 reference statements)

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“…Genetic variants and mutations in the genes coding for ANP or its receptor have been found in patients with hypertension and heart disease 35 36 37 38 39 40 41 . Corin acts as the pro-ANP convertase at the top of the ANP pathway 7 24 42 43 . Here we report a novel CORIN variant allele that is present preferentially in hypertensive patients.…”

Section: Discussionmentioning

confidence: 99%

A Corin Variant Identified in Hypertensive Patients That Alters Cytoplasmic Tail and Reduces Cell Surface Expression and Activity

Zhang

Zhou

et al. 2014

Sci Rep

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Corin is a membrane-bound protease that regulates blood pressure by activating the natriuretic peptides. CORIN variants have been associated with hypertension and heart disease in African Americans. In this study, we conducted targeted exome sequencing and identified an insertion variant, c.102_103insA, in exon 1 of the CORIN gene. Analysis of two independent cohorts showed that the variant was preferentially present in hypertensive patients (38/795 or 4.78% vs. 4/632 or 0.63% in normal individuals, p = 4.14E-6). The insertion shifted the reading frame, resulting in a corin variant with a truncated cytoplasmic tail. In cell-based studies, the corin variant exhibited poor trafficking in the Golgi, reduced cell surface expression and zymogen activation, and low natriuretic peptide processing activity. Compared with normal individuals with the wild-type allele, individuals with the variant allele had lower levels of plasma corin [0.59 ± 0.07 ng/mL (n = 25) vs. 0.91 ± 0.02 ng/mL (n = 215), p<0.001] and higher levels of plasma N-terminal pro-atrial natriuretic peptide (NT-pro-ANP) [2.39 ± 3.6 nmol/L (n = 21) vs. 0.87 ± 0.6 nmol/L (n = 48), p = 0.005]. These results indicate that the variant altered corin structure and impaired the natriuretic peptide processing activity in vivo. The results highlight corin defects as an important underlying mechanism in hypertension.

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Section: Discussionmentioning

confidence: 99%

A Corin Variant Identified in Hypertensive Patients That Alters Cytoplasmic Tail and Reduces Cell Surface Expression and Activity

Zhang

Zhou

et al. 2014

Sci Rep

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“…The catalytic or proteolytic activity of corin is attributed to its C-terminal trypsin-like serine protease domain. Biologically active ANP is released in circulation and binds to the natriuretic peptide-A receptor in kidneys and vasculature [27]. This binding leads to receptor activation and generation of 3 -5 -cyclic guanosine monophosphate (cGMP) and directly inhibits renin release from the kidneys promoting natriuresis, diuresis, and vasodilation [28][29][30].…”

Section: Introductionmentioning

confidence: 99%

Cardiac-Specific Overexpression of Catalytically Inactive Corin Reduces Edema, Contractile Dysfunction, and Death in Mice with Dilated Cardiomyopathy

Tripathi

Sullivan

Fan

et al. 2019

IJMS

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Humans with dilated cardiomyopathy (DCM) and heart failure (HF) develop low levels of corin, a multi-domain, cardiac-selective serine protease involved in natriuretic peptide cleavage and sodium and water regulation. However, experimental restoration of corin levels markedly attenuates HF progression. To determine whether the beneficial effects of corin in HF require catalytic activity, we engineered cardiac overexpression of an enzymatically inactive corin transgene (corin-Tg(i)). On a wild-type (WT) background, corin-Tg(i) had no evident phenotypic effects. However, in a well-established genetic model of DCM, corin-Tg(i)/DCM mice had increased survival (p < 0.01 to 0.001) vs. littermate corin-WT/DCM controls. Pleural effusion (p < 0.01), lung edema (p < 0.05), systemic extracellular free water (p < 0.01), and heart weight were decreased (p < 0.01) in corin-Tg(i)/DCM vs. corin-WT/DCM mice. Cardiac ejection fraction and fractional shortening improved (p < 0.01), while ventricular dilation decreased (p < 0.0001) in corin-Tg(i)/DCM mice. Plasma atrial natriuretic peptide, cyclic guanosine monophosphate, and neprilysin were significantly decreased. Cardiac phosphorylated glycogen synthase kinase-3β (pSer9-GSK3β) levels were increased in corin(i)-Tg/DCM mice (p < 0.01). In summary, catalytically inactive corin-Tg(i) decreased fluid retention, improved contractile function, decreased HF biomarkers, and diminished cardiac GSK3β activity. Thus, the protective effects of cardiac corin on HF progression and survival in experimental DCM do not require the serine protease activity of the molecule.

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“…In mice, PCSK6 deficiency leads to salt-sensitive hypertension [18]. These data indicate that the corin-ANP pathway is critical for sodium homeostasis and normal blood pressure [19–22]. …”

Section: Introductionmentioning

confidence: 99%

Localization of corin and atrial natriuretic peptide expression in human renal segments

et al. 2016

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Atrial natriuretic peptide (ANP)-mediated natriuretic response is a well-established cardiac endocrine function. Corin is a transmembrane protease that activates ANP in the heart. Corin expression has been detected in non-cardiac tissues including the kidney. Here we examined corin, pro-ANP/ANP and natriuretic peptide receptor-A (NPR-A) expression in human renal segments. By immunostaining and in situ hybridization, we found similar corin, pro-ANP/ANP and NPR-A protein and mRNA expression in human renal segments. The expression was most abundant in the proximal convoluted tubules and the medullary connecting ducts. In the proximal tubules, corin protein was present in the apical membrane region underneath the brush border where the ANP-degrading protease neprilysin was abundant. These results suggest that corin-mediated pro-ANP activation may occur in renal segments and that locally produced ANP may act in an autocrine manner to regulate sodium and water reabsorption in situ. Our results also point to the proximal convoluted tubules as a major site for local ANP action. Such a renal corin/ANP autocrine mechanism may differ from the cardiac corin/ANP endocrine mechanism in regulating sodium homeostasis under physiological and pathological conditions.

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Corin

Cited by 43 publications

References 77 publications

A Corin Variant Identified in Hypertensive Patients That Alters Cytoplasmic Tail and Reduces Cell Surface Expression and Activity

A Corin Variant Identified in Hypertensive Patients That Alters Cytoplasmic Tail and Reduces Cell Surface Expression and Activity

Cardiac-Specific Overexpression of Catalytically Inactive Corin Reduces Edema, Contractile Dysfunction, and Death in Mice with Dilated Cardiomyopathy

Localization of corin and atrial natriuretic peptide expression in human renal segments

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