Corin Levels Research Articles

Circulating corin concentration is associated with risk of mortality and acute kidney injury in critically ill patients

Elevated serum corin concentrations in patients with cardiac diseases have been associated with adverse cardiovascular events and progressive renal dysfunction. This study aimed to determine the role of serum corin levels in predicting the incidence of acute kidney injury (AKI) and mortality in critically ill patients admitted to intensive care units (ICUs). We screened 323 patients admitted to the ICU in our institution from May 2018 through December 2019. After excluding patients receiving renal replacement therapy, 288 subjects were enrolled. Cases were divided equally into high (n = 144) and low (n = 144) corin groups according to median serum corin levels, using 910 pg/mL as the cut-off point. Patient characteristics and comorbidities were collected from medical records. The primary outcome was AKI within 48 h after ICU admission, while the secondary outcome was all-cause of mortality within 1 year. Compared with the low corin group, patients in the high corin group had higher prevalence rates of diabetes, cirrhosis, and nephrotoxic agent exposure; higher Sequential Organ Failure Assessment scores, white blood cell counts, proteinuria, and serum N-terminal pro-brain natriuretic peptide levels; but had lower initial estimated glomerular filtration rates. Furthermore, elevated serum corin was associated with higher risks of AKI within 48h of ICU admission (43.1% vs. 18.1%, p < 0.001) and all-cause mortality within one year (63.9% vs. 50.0%, p = 0.024). High corin level showed strongly positive results as an independent predictor of AKI (OR 2.15, 95% CI 1.11–4.19, p = 0.024) but not for the all-cause mortality after adjusting for confounding factors in multivariate analyses. Elevated circulating corin predicted AKI in critically ill patients, but did not predict all-cause mortality within 1 year. As a key enzyme in renin–angiotensin–aldosterone system, corin expression may be regulated through a feedback loop following natriuretic peptide resistance and desensitization of natriuretic peptide receptors in different critically ill status.

Plasma Corin: A New Biochemical Marker for Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder. Atrial natriuretic peptide (ANP) is a risk factor for PCOS. Corin protein has an essential role in ANP synthesis. This study aimed to evaluate corin as a sensitive biomarker for PCOS. A case-control study was conducted with 70 PCOS patients and 70 healthy females. Plasma Corin levels were quantified using enzyme-linked immunosorbent assay. The median plasma corin levels in PCOS patients and controls were 1785 and 822.5 pg/mL, respectively. Plasma corin levels were significantly elevated in PCOS patients than in the controls (p < 0.001). The optimal cut-off value was set at 1186 pg/mL. The sensitivity and specificity of Corin were 100% and 97.1%, respectively. Plasma corin levels were surrogate predictors for infertility in women with PCOS. It had an odds ratio of 5.9 (95% confidence interval: 1.1-32.7) (p = 0.04). Plasma corin levels were more highly detected in patients with PCOS than in the controls. Plasma corin level has reasonable diagnostic interpretation for PCOS. Corin appears as a worthy distinct predictor of infertility in PCOS women. Therefore, Corin may be a substantial biomarker for PCOS.

Corin and Left Atrial Cardiomyopathy, Hypertension, Arrhythmia, and Fibrosis

SummaryTwo siblings presented with cardiomyopathy, hypertension, arrhythmia, and fibrosis of the left atrium. Each had a homozygous null variant in CORIN, the gene encoding atrial natriuretic peptide (ANP)–converting enzyme. A plasma sample obtained from one of the siblings had no detectable levels of corin or N-terminal pro-ANP but had elevated levels of B-type natriuretic peptide (BNP) and one of the two protein markers of fibrosis that we tested. These and other findings support the hypothesis that BNP cannot fully compensate for a lack of activation of the ANP pathway and that corin is critical to normal ANP activity, left atrial function, and cardiovascular homeostasis.

Corin-The Early Marker of Preeclampsia in Pregestational Diabetes Mellitus.

Preeclampsia (PE) is one of the leading causes of mortality and morbidity in pregnant women. Pregestational diabetes (PGDM) patients are prone to vascular complications and preeclampsia, whereas vascular exposure to hyperglycemia induces inflammation, vascular remodeling, and arterial stiffness. Corin is a serine protease, converting inactive pro-atrial natriuretic peptide (pro-ANP) into an active form. It also promotes salt and water excretion by activating atrial natriuretic peptide (ANP), and significantly increases trophoblast invasion. The study aimed to determine whether corin may be a predictor of PE in a high-risk group-women with long-term PGDM. The nested case-control prospective study involved 63 patients with long-term pregestational type 1 diabetes (PGDM). In total, 17 patients developed preeclampsia (the study group), whereas 43 patients without PE constituted the control group. To assess corin concentration, blood samples were collected at two time points: between 18th-22nd week of gestation and 28th-32nd week of gestation. PE patients presented significantly higher mid-gestation corin levels, urine protein loss in each trimester, serum creatinine in the third trimester, and lower creatinine clearance in the third trimester. The results of our study indicate that serum corin assessment may play a role in predicting preeclampsia. Thus, it may be included in the PE risk calculator, initially in high-risk groups, such as patients with PGDM.

Corin is regulated by circ-0012397/miR-200a-3p and inhibits the oxygen-glucose deprivation-induced apoptosis of SHSY5Y neuroblastoma cells

As a type II transmembrane serine protease, corin plays a role in several important physiological and pathological processes. We conducted a bioinformatics analysis to explore the roles of both corin and circ-0012397/miR-200a-3p in ischemic stroke. We established an in vitro model using oxygen-glucose deprivation (OGD)-induced SHSY5Y cells. The proliferation and apoptosis of SHSY5Y cells was determined using Cell Counting Kit-8 (CCK-8) and flow cytometry/Hoechst 33258 staining, respectively. The RNA and protein level was tested using Real Time Quantitative Polymerase Chain Reaction (RT-qPCR) and western blot, respectively. The regulatory relationship of corin and circ-0012397/miR-200a-3p were detected by dual-luciferase reporter assays. We found that OGD downregulated the expression of corin in a time-dependent manner; this change was inversely proportional to the rate of apoptosis of the SHSY5Y cells. Further, high expression levels of corin enhanced the proliferation of SHSY5Y cells and inhibited the apoptosis of SHSY5Y cells by downregulating the expression of cleaved caspase-3, B-cell lymphoma 2 (BCL-2)-associated death promoter, extracellular-regulated protein kinase (ERK), and protein 38 (p38), and upregulated the expression of Bcl-2. Further, the dual-luciferase reporter assays and RT-qPCR showed that corin expression was regulated by circ-0012397/miR-200a-3p. Corin expression was affected by changes in circ-0012397 and miR-200a-3p expression, which were overexpressed or inhibited. Further, corin exerted different regulatory effects on apoptosis signaling-related proteins, including AD Bcl-2, cleaved caspase-3, ERK, and p38, under different expression levels of circ-0012397 and miR-200a-3p. Corin promotes the cell proliferation and inhibits OGD-induced apoptosis of SHSY5Y cells, and that its expression is regulated by circ-0012397/miR-200a-3p. Thus, corin may be a potential target for ischemic stroke patients.

Association between CORIN methylation and hypertension in Chinese adults

BackgroundCorin, a physical activator of atrial natriuretic peptide, has been associated with hypertension with unclear mechanisms. Here, we aimed to examine whether CORIN gene methylation was involved in the underlying...

Chronic Kidney Disease Is Associated With Increased Cardiac Corin Expression But Decreased Proatrial Natriuretic Peptide Conversion Activity.

Background Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease. Corin converts proatrial natriuretic peptide into its active form after being activated by PCSK6 (proprotein convertase subtilisin/kexin type 6) protease. It remains unknown whether the PCSK6/corin/atrial natriuretic peptide pathway plays a role in CKD-induced cardiomyopathy. Methods and Results Serum corin, left ventricular mass index, and corin-left ventricular mass index correlation were compared between outpatients with versus without CKD. Cardiac corin expression and activity as well as serum corin were compared between 5/6 nephrectomy CKD animal models and sham controls. The effects of indoxyl sulfate, a uremic toxin, on cardiomyocytes were examined in vitro in H9c2 cells. A total of 543 patients were enrolled in this study. Serum corin levels were elevated in patients with CKD compared with levels in patients without CKD. Serum corin levels correlated negatively with left ventricular mass index in participants without CKD, but not in patients with CKD. Compared with sham controls, CKD mice had higher serum corin levels and increased cardiac expression of corin but reduced cardiac corin conversion activity. Indoxyl sulfate stimulated corin expression while suppressing serine protease activity in H9c2 cardiomyoblasts. Lower PCSK6 expression in CKD mouse hearts and indoxyl sulfate-treated H9c2 cardiomyoblasts may explain, at least partly, the observed CKD-associated reduction in corin activity. Conclusions In CKD, cardiac and serum levels of corin are increased, yet corin activity is suppressed. The latter may be attributable to reduced PCSK6 expression. These findings suggest that corin dysfunction may play a significant role in the pathogenesis of CKD-associated cardiomyopathy.

Low serum corin levels predict end-organ damage in patients with hypertensive crisis

The study aimed to investigate the predictive power of serum corin levels for distinguishing between hypertensive urgency (HU) and hypertensive emergency (HE) in patients with hypertensive crisis (HC) admitted to the emergency department. A total of 120 consecutive consenting adult patients diagnosed with HC and 55 age- and sex-matched healthy controls were enrolled. Blood pressure measurements [(systolic, diastolic, and mean arterial pressure (MAP)] and the evidence of end-organ damage at the first admission were recorded. Patients with HC were classified as patients with HE or HU according to the presence or absence of acute end-organ damage. Serum corin levels were compared between the 2 groups. The mean serum corin level was significantly lower in the HC group than in the control group; it was also lower in the HE group than in the HU group (p<0.001 for all). In the HE group, clinical features associated with end-organ damage included ST-elevation myocardial infarction (n=28, 46.7%), hemorrhagic stroke (n=11, 18.3%), ischemic stroke (n=11, 18.3%), and non-ST-elevation myocardial infarction (n=10, 16.7%). The receiving operator characteristic (ROC) analysis identified a serum corin cutoff value of 45 pg/mL for distinguishing patients with HE from patients with HU with 98.3% sensitivity and 95% specificity. Our findings suggest that serum corin levels play an important role in regulating blood pressure and are involved in the pathogenesis of HC. Low serum corin levels may predict end-organ damage and serve as a guide for diagnostic decision making in patients with HC.

RESECTION OF THE ATRIAL APPENDAGES AND ITS IMPACT IN THE NATRIURETIC HOMEOSTASIS: DEVELOPMENT AND VALIDATION OF AN ANIMAL MODEL IN AN ACADEMIC MEDICAL CENTER.

The left atrial appendage (LAAp) resection is an effective treatment approach to reduce the risk of thromboembolism in patients with atrial fibrillation. To study was to study the impact of removing atrial appendages in the production of natriuretic peptides (NPs) in conditions of volume overload and to develop an experimental model of LAAp resection. In a swine model of ischemic heart failure (HF), serum NP levels were measured before (Basal-1A) and after (Basal-1B) a fluid overload. Animals were grouped as follows: (0) preserved appendages, (1) resected LAAp, and (2) both atrial appendages resected. Levels of NP were measured before (2A) and after a fluid overload (2B). Furin levels were higher in Group 0-2A than in Group 2-2A, and a significant increase was found in Group 0-2B compared to Groups 1-2B and 2-2B. Corin levels increased in Basal-1B versus Basal-1A. Atrial NP (ANP) decreased in Basal-1B compared to Basal-1A. After HF induction, ANP increased in Groups 2-2A and 2-2B. Resection of atrial appendages drastically modifies the natriuretic mechanisms of cardiac homeostasis, especially after a fluid overload challenge. Herein, we describe the face and predictive validation of an animal model of atrial appendage resection useful to investigations in translational medicine.

Placental Overexpression of Soluble CORIN in Preeclampsia

Preeclampsia (PE) is a hypertensive disease of pregnancy associated with substantial maternal and fetal morbidity and mortality. CORIN is a transmembrane type II serine protease expressed in cardiomyocytes that converts pro-atrial natriuretic peptide into atrial natriuretic peptide, a cardiac hormone that regulates blood pressure. High levels of soluble CORIN have been reported in PE and are supposed to be cardiac in origin. We hypothesized that during pregnancy soluble CORIN is released by the syncytiotrophoblast and that increased levels of soluble CORIN in preeclampsia originate from placenta. A total of 375 patients (181 PE patients and 194 controls) were analyzed. High levels of soluble CORIN were confirmed in maternal blood from preeclamptic pregnancies compared with controls. Differentiated primary villous cytotrophoblasts showed that CORIN was expressed (mRNA and protein levels) and secreted by trophoblastic cells, mostly by the syncytiotrophoblast. Finally, placental explants showed a significant increase in CORIN production and secretion in PE cases compared with controls. This study showed that CORIN is secreted by trophoblastic cells and that high levels of soluble CORIN in preeclampsia have a placental origin.

Effect of pulmonary vein catheter ablation on kidney function in patients with atrial fibrillation. A prospective cohort study.

Several studies have linked the presence of atrial fibrillation (AF) with reduced estimated glomerular filtration rate (eGFR). Our objective was to compare changes in eGFR in patients with AF after pulmonary vein (PV) ablation depending on the success of the technique, as well as to examine the relationship between eGFR and several biomarkers. Prospective cohort of patients with AF referred to our center for PV ablation with a 1-year follow-up. We estimated eGFR using the Chronic Kidney Disease Epidemiology Collaboration formula at baseline and at 3 and 12 months. Biomarkers (B-type natriuretic peptide, corin, and galectin-3) were measured before ablation and at 12 months. We studied 124 patients (age 55±10 years, 69.4% men). Seventy-five had paroxysmal AF (60.5%). The mean baseline eGFR was 90.8 [77.8-100.0] mL/min/1.73 m2. The eGFR increased at the end of follow-up, with a statistically significant difference between patients with recurrence at 12 months and those without (-1.1 [-6.0 to 8.8] mL/min/1.73 m2 vs 7.1 [-0.6 to 14.2] mL/min/1.73 m2, P=.017). The improvement in eGFR at 12 months was inversely proportional to baseline eGFR. B-type natriuretic peptide and corin levels improved at 12 months, while galectin-3 levels worsened, which was unrelated to eGFR. In patients with AF treated with PV ablation, an overall improvement in eGFR was observed, which was more marked in the subgroup without recurrences, although without significant differences on multivariate analysis.

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

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.

Serum PCSK6 and corin levels are not associated with cardiovascular outcomes in patients undergoing coronary angiography.

IntroductionProprotein convertase subtilisin/kexin-6 (PCSK6) is a secretory protein that activates corin in the heart. Higher circulating levels of corin are associated with improved cardiovascular outcomes in patients with acute myocardial infarction. This study aimed to determine the role of serum PCSK6 and corin levels in predicting cardiovascular outcomes in patients with suspected coronary artery disease (CAD).Materials and methodsIn total, 565 patients who had undergone coronary angiography were enrolled. Serum PCSK6 and corin levels were determined before the administration of contrast media. In this study, coronary revascularization, acute myocardial infarction, acute stroke, and death were defined as cardiovascular outcomes. All patients were followed up for at least one year after coronary angiography or until the occurrence of death.ResultsDuring a median follow-up of 691 days, 67 patients (15.7%) developed composite cardiovascular outcomes after coronary angiography, including 51 incidents of coronary revascularization, 7 instances of acute myocardial infarction, 2 acute strokes, and 15 deaths. After adjustment for demographic characteristics and all significant variables in the univariate analysis, serum levels of neither PCSK6 nor corin were associated with increased risk for cardiovascular outcomes. This correlation remained insignificant in patients with underlying hypertension, diabetes mellitus, CAD, heart failure, or chronic kidney disease (CKD). However, in patients without CKD, higher serum PCSK6 levels were associated with increased risk for cardiovascular outcomes (hazard ratio 1.380; 95% confidence interval 1.023–1.862).ConclusionsWe found no association between cardiovascular outcomes and pre-procedural serum levels of PCSK6 or corin in patients undergoing coronary angiography. However, an increased risk was seen in non-CKD patients with higher PCSK6 levels. Further studies are needed to verify these results.

Associations between potentially functional CORIN SNPs and serum corin levels in the Chinese Han population

BackgroundCorin is an important convertase involved in the natriuretic peptide system and may indirectly regulate blood pressure. Genetic factors relate to corin remain unclear. The purpose of the current study was to comprehensively examine the associations among CORIN SNPs, methylations, serum corin levels and hypertension.ResultsWe genotyped 9 tag-SNPs in the CORIN gene and measured serum corin levels in 731 new-onset hypertensive cases and 731 age- and sex-matched controls. DNA methylations were tested in 43 individuals. Mendelian randomization was used to investigate the causal associations. Under additive models, we observed associations of rs2289433 (p.Cys13Tyr), rs6823184, rs10517195, rs2271037 and rs12509275 with serum corin levels after adjustment for covariates (P = 0.0399, 0.0238, 0.0016, 0.0148 and 0.0038, respectively). The tag-SNP rs6823184 and SNPs that are in strong linkage disequilibrium with it, i.e., rs10049713, rs6823698 and rs1866689, were associated with CORIN gene expression (P = 2.38 × 10− 24, 5.94 × 10− 27, 6.31 × 10− 27 and 6.30 × 10− 27, respectively). Neither SNPs nor corin levels was found to be associated with hypertension. SNP rs6823184, which is located in a DNase hypersensitivity cluster, a CpG island and transcription factor binding sites, was significantly associated with cg02955940 methylation levels (P = 1.54 × 10− 7). A putative causal association between cg02955940 methylation and corin levels was detected (P = 0.0011).ConclusionThis study identified potentially functional CORIN SNPs that were associated with serum corin level in the Chinese Han population. The effect of CORIN SNPs on corin level may be mediated by DNA methylation.

Efecto de la ablación con catéter de venas pulmonares en la función renal de pacientes con fibrilación auricular. Estudio de cohortes prospectivo

Introduction and objectivesSeveral studies have linked the presence of atrial fibrillation (AF) with reduced estimated glomerular filtration rate (eGFR). Our objective was to compare changes in eGFR in patients with AF after pulmonary vein (PV) ablation depending on the success of the technique, as well as to examine the relationship between eGFR and several biomarkers. MethodsProspective cohort of patients with AF referred to our center for PV ablation with a 1-year follow-up. We estimated eGFR using the Chronic Kidney Disease Epidemiology Collaboration formula at baseline and at 3 and 12 months. Biomarkers (B-type natriuretic peptide, corin, and galectin-3) were measured before ablation and at 12 months. ResultsWe studied 124 patients (age 55±10 years, 69.4% men). Seventy-five had paroxysmal AF (60.5%). The mean baseline eGFR was 90.8 [77.8-100.0] mL/min/1.73 m2. The eGFR increased at the end of follow-up, with a statistically significant difference between patients with recurrence at 12 months and those without (−1.1 [-6.0 to 8.8] mL/min/1.73 m2 vs 7.1 [−0.6 to 14.2] mL/min/1.73 m2, P=.017). The improvement in eGFR at 12 months was inversely proportional to baseline eGFR. B-type natriuretic peptide and corin levels improved at 12 months, while galectin-3 levels worsened, which was unrelated to eGFR. ConclusionsIn patients with AF treated with PV ablation, an overall improvement in eGFR was observed, which was more marked in the subgroup without recurrences, although without significant differences on multivariate analysis.

Normalizing Plasma Renin Activity in Experimental Dilated Cardiomyopathy: Effects on Edema, Cachexia, and Survival.

Heart failure (HF) patients frequently have elevated plasma renin activity. We examined the significance of elevated plasma renin activity in a translationally-relevant model of dilated cardiomyopathy (DCM), which replicates the progressive stages (A–D) of human HF. Female mice with DCM and elevated plasma renin activity concentrations were treated with a direct renin inhibitor (aliskiren) in a randomized, blinded fashion beginning at Stage B HF. By comparison to controls, aliskiren treatment normalized pathologically elevated plasma renin activity (p < 0.001) and neprilysin levels (p < 0.001), but did not significantly alter pathological changes in plasma aldosterone, angiotensin II, atrial natriuretic peptide, or corin levels. Aliskiren improved cardiac systolic function (ejection fraction, p < 0.05; cardiac output, p < 0.01) and significantly reduced the longitudinal development of edema (extracellular water, p < 0.0001), retarding the transition from Stage B to Stage C HF. The normalization of elevated plasma renin activity reduced the loss of body fat and lean mass (cachexia/sarcopenia), p < 0.001) and prolonged survival (p < 0.05). In summary, the normalization of plasma renin activity retards the progression of experimental HF by improving cardiac systolic function, reducing the development of systemic edema, cachexia/sarcopenia, and mortality. These data suggest that targeting pathologically elevated plasma renin activity may be beneficial in appropriately selected HF patients.

The role of G protein-associated estrogen receptor (GPER) 1, corin, raftlin, and estrogen in etiopathogenesis of intrauterine growth retardation

Objective: The aim of the present study was to detect the role of G protein-associated estrogen receptor (GPER) 1, corin, raftlin and estrogen in etiopathogenesis of intrauterine growth retardation (IUGR).Materials and methods: The present study was designed prospectively between January 2017 and May 2018. The study group included 32 patients with unexplained IUGR and 32 healthy pregnant women who gave birth at term among the patients who referred to obstetrics clinic of a tertiary reference hospital. Intrauterine growth retardation (IUGR) was accepted as birth weight below 10th percentile according to the estimated fetal weight. Exclusion criteria were as follows: the patients with renal or hepatic dysfunction, presence of any chronic disease, smoker patients, preeclampsia, acute or chronic inflammatory diseases, body mass index as <18 kg/m2 and >25 kg/m2, structural or chromosomal abnormality in fetus Estradiol (E2), estriol (E3), GPER, corin, and raftlin levels were analyzed in maternal serum and placental tissue homogenate through ELISA method.Results: Serum levels of GPER-1, raftlin, and E3 were significantly lower in IUGR group when compared with the control group (p < .05 for all). Serum corin and E2 levels were similar between two groups. GPER-1, E2, E3, raftlin, and corin levels in placental homogenate were found significantly higher in the control group (p < .05 for all).Conclusion: Although maternal, fetal, and placental causes take place in etiopathogenesis of IUGR, exact etiological factor is not revealed in majority of the IUGR cases. The present study serves as the first study revealing the role of the decrease in GPER-1 and raftlin in maternal serum and placental levels on the etiopathogenesis of IUGR. Furthermore, the decrease in placental corin expression of the cases with IUGR was detected first in the literature. The present study reveals a potential therapeutic use of GPER-1, corin, and raftlin for IUGR.

Circulating NT-proBNP but not soluble corin levels were associated with preeclampsia in pregnancy-associated hypertension

BackgroundCorin is a serine protease known to convert B-type natriuretic peptide (BNP) prohormone into BNP and its amino-terminal fragment (NT-proBNP). In mice lacking corin, high blood pressure and proteinuria were found at late gestational stages, with associated delayed trophoblast invasion and impaired spiral artery remodeling in the uterus. We hypothesize that both NT-proBNP and soluble corin elevation predict the presence of preeclampsia in pregnant patients with hypertension. MethodsWe prospectively enrolled 149 pregnant women with a history of chronic hypertension or gestational hypertension presenting at a tertiary-care hospital. We compared plasma NT-proBNP and soluble corin concentrations based on their preeclamptic status. ResultsIn our study cohort, 62 patients with preeclampsia had lower gestational age than 87 patients without preeclampsia (33.3 ± 3 versus 36.6 ± 3 weeks; P < .001), otherwise the baseline characteristics were similar. We observed higher NT-proBNP concentrations in patients with preeclampsia compared to those without preeclampsia (304.3 [96.34, 570.4] vs. 60.8 [35.61, 136.8] ng/L, P < .001), with no differences between chronic and gestational hypertension. However, the concentration of corin was not statistically different between the two groups (1756 [1214, 2133] vs. 1571 [1171, 1961] ng/L, P = .1087). ROC curve analysis demonstrated stronger predictive value of NT-proBNP compared to soluble corin in predicting the presence of preeclampsia in our study population (AUC 0.7406 vs. 0.5789, P < .0001). ConclusionWhile corin may contribute to mechanistic underpinnings of the development of preeclampsia in animal models, soluble corin likely has no diagnostic role in human pregnancies for preeclampsia beyond natriuretic peptide levels.

Corin Is Downregulated in Renal Ischemia/Reperfusion Injury and Is Associated with Delayed Graft Function after Kidney Transplantation.

Renal ischemia/reperfusion (IR) injury is one of the most important risk factors for the occurrence of delayed graft function (DGF) after kidney transplantation; however, its mechanism remains not fully understood. In the present study, we screened differentially expressed genes in a murine model of renal IR injury by using high-throughput assays. We identified Corin as one of the most significantly downregulated genes among 2218 differentially expressed genes (≥2-fold, P < 0.05). By using a real-time qPCR assay, we observed that the expression of renal Corin in IR-injured mice was reduced to 11.5% of the sham-operated mice and that the protein level of renal Corin in IR-injured mice was also downregulated. Interestingly, renal IR injury in mice induced the downregulation of Corin in heart tissues, suggesting that the overall synthesis of Corin may be suppressed. We recruited 11 recipients complicated with DGF and 16 without DGF, and plasma Corin concentrations were determined by ELISA. We observed that the plasma Corin levels were indeed reduced in recipients complicated with DGF (0.98 vs. 1.95 ng/ml, P < 0.05). These findings demonstrate that Corin may be a potential biomarker of DGF after kidney transplantation and may participate in the regulation of renal IR injury.

Maternal Serum Concentrations of Corin, Endoglin, PP13, and sFlt-1 and their Changes with Advancement of Pregnancy and Correlation with Doppler of Uterine Arteries.

Pre-eclampsia (PE) affects 2% to 5% of all pregnancies and is a major cause of maternal and perinatal morbidity and mortality worldwide. Since PE has complex pathogenesis and treatment is still not found, effective methods for prediction and prevention of PE are still actively searched. The aim of this study was to find the mean maternal serum concentration of four proteins in Bulgarian pregnant women and to investigate the correlation with uterine artery pulsatility index in the first and second trimester of pregnancy. In this prospective case-control study, maternal serum concentrations of corin, sEndoglin, PP13, and sFlt-1 were measured, pulsatility index of uterine artery (PI-UA) was assessed in 40 women with Doppler, twice during pregnancy - at the 11th - 13th weeks of gestation and the 20th gestational week. They were randomized in two groups: an experimental group: with increased PIUA at gestational week 13 and a control group: with normal PI-UA. All pregnancies were followed up until the day of delivery and outcomes were recorded. There was no significant difference in the APGAR score and birth weight of the newborns between groups. We found no significant difference in the mean concentration of sEnd, sFlt-1 and PP13 between 11-13 weeks of gestation and 20 week of gestation in the control and experimental groups. Statistically significant difference was found only in the mean concentrations of corin between weeks 11-13 and week 20 in both control (t=3.27; p=0.004) and experimental group (t=3.22; p=0.005). Corin levels and the mean PI of uterine arteries tended to decrease with progression of pregnancy in both groups. Further prospective studies of larger populations are required to develop a panel of multiple predictors for PE.