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

Yang, Shang‐Feng; Chou, Ruey‐Hsing; Lin, Shing Jong; Li, Szu Yuan; Huang, Po Hsun

doi:10.1371/journal.pone.0226129

Cited by 9 publications

(8 citation statements)

References 28 publications

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“…High levels of BNP-precociously highlighting a volume overload-reflect a high venous return and diastolic dysfunction which (associated with renal failure) increase pulmonary venous and arterial pressures, representing the hemodynamic prelude of PH [31]. Consequently, the progressive increase of BNP and the decrease in renal function are necessarily associated with pulmonary involvement, amplifying the progression of both cardiac and kidney failure, leading to ESRD and chronic heart failure [32].…”

Section: Discussionmentioning

confidence: 99%

Left Ventricular Mass Index Predicts Renal Function Decline in Patients with Chronic Kidney Disease

Lacquaniti,

Ceresa,

Campo

et al. 2024

Medicina

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Background and Objectives: Several studies revealed a relation between abnormal cardiac remodeling and glomerular filtration rate (GFR) decline, but there are limited data regarding echocardiographic changes in chronic kidney disease (CKD). This study evaluated the abnormal cardiac structures characterizing patients with CKD, assessing the independent association between echocardiographic parameters and the risk of decline in renal function. Materials and Methods: In total, 160 patients with CKD were studied. All patients underwent an echocardiographic exam and 99mTc-DTPA renal scintigraphy to measure the GFR. After the baseline assessments, patients were followed prospectively for 12 months, or until the endpoint achievement, defined as a worsening in renal function (doubling of baseline serum creatinine, GFR decline ≥25%, the start of dialysis). Results: Patients with GFR values of 34.8 ± 15 mL/min, identifying stages III–IV of CKD, were associated with high levels of left ventricular mass index (LVMi) (101.9 ± 12.2 g/m2), which was related to proteinuria, systolic blood pressure, and pulmonary artery systolic pressure in a multiple regression model. During the observational period, 26% of patients reached the endpoint. Regression analysis revealed LVMi as a predictor of change in renal function after adjusting for kidney and cardiac risk factors. Multiple Cox regression indicated that an increase in LVMi was associated with a 12% increased risk of kidney disease progression (HR: 1.12; 95% CI: 1.04–1.16; p = 0.001). Conclusions: In patients with CKD, high LVMi represents an independent predictor of the progressive decline of the renal function, until the start of renal replacement therapy. Echocardiography can help identify patients at high risk for renal disease worsening in patients with CKD independently of clinical cardiac involvement.

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Section: Discussionmentioning

confidence: 99%

Left Ventricular Mass Index Predicts Renal Function Decline in Patients with Chronic Kidney Disease

Lacquaniti,

Ceresa,

Campo

et al. 2024

Medicina

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“…It was published that PACE4 (PCSK6) is very sensitive to even moderately high temperatures such as 37 °C ( 61 ). And finally, we and others have shown that PCSK6 is present in the blood as a soluble protein ( 55 , 56 ), whereas PCSK5 (PC5A) is not, or at least no one could detect it. Taken together, PCSK6 (PACE4) emerges as possibly the sole, or at least the major activator of MASP-3 in human blood.…”

Section: Complement Proteins Processes By Proprotein Convertases and ...mentioning

confidence: 93%

“…Blocking PCSK6 secretion by monensin and subsequent immunostaining indicated that corin and PCSK6 were secreted via different intracellular pathways, which may explain the lack of corin activation inside the cell. The detection of secreted PCSK6 in the human blood indicated that PCSK6 may process other proteins in the circulation thereby modulating the effect of the proteolytic cascade systems ( 56 ).…”

Section: Complement Proteins Processes By Proprotein Convertases and ...mentioning

confidence: 99%

“…PCSK9 is also included, as a well-known example of a PC present at high levels in the blood, despite being in a proteolytically inactive (inhibited) state. PACE4 has been also detected in the blood ( 55 , 56 ), while so far no one reported the presence of PC5A in the blood, however it could be present in other extracellular fluids.…”

Section: Brief Introduction To Mammalian Proprotein Convertasesmentioning

confidence: 99%

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Proprotein Convertases and the Complement System

et al. 2022

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Proteins destined for secretion - after removal of the signal sequence - often undergo further proteolytic processing by proprotein convertases (PCs). Prohormones are typically processed in the regulated secretory pathway, while most plasma proteins travel though the constitutive pathway. The complement system is a major proteolytic cascade in the blood, serving as a first line of defense against microbes and also contributing to the immune homeostasis. Several complement components, namely C3, C4, C5 and factor I (FI), are multi-chain proteins that are apparently processed by PCs intracellularly. Cleavage occurs at consecutive basic residues and probably also involves the action of carboxypeptidases. The most likely candidate for the intracellular processing of complement proteins is furin, however, because of the overlapping specificities of basic amino acid residue-specific proprotein convertases, other PCs might be involved. To our surprise, we have recently discovered that processing of another complement protein, mannan-binding lectin-associated serine protease-3 (MASP-3) occurs in the blood by PCSK6 (PACE4). A similar mechanism had been described for the membrane protease corin, which is also activated extracellularly by PCSK6. In this review we intend to point out that the proper functioning of the complement system intimately depends on the action of proprotein convertases. In addition to the non-enzymatic components (C3, C4, C5), two constitutively active complement proteases are directly activated by PCs either intracellularly (FI), or extracellularly (MASP-3), moreover indirectly, through the constitutive activation of pro-factor D by MASP-3, the activity of the alternative pathway also depends on a PC present in the blood.

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“…These data support a role of PCSK6 in a paracrine mechanism, underlying cardiac remodeling after MI. In another study [ 138 ], serum PCSK6 levels were associated with cardiovascular events in a subset of patients undergoing coronary angiography. Further studies will be important to evaluate if serum PCSK6 can be used as a biomarker to predict cardiac remodeling and function in patients with heart disease.…”

Section: Pcsk6 and Cardiovascular Pathophysiologymentioning

confidence: 99%

Proprotein Convertase Subtilisin/Kexin 6 in Cardiovascular Biology and Disease

Chen

2022

IJMS

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Proprotein convertase subtilisin/kexin 6 (PCSK6) is a secreted serine protease expressed in most major organs, where it cleaves a wide range of growth factors, signaling molecules, peptide hormones, proteolytic enzymes, and adhesion proteins. Studies in Pcsk6-deficient mice have demonstrated the importance of Pcsk6 in embryonic development, body axis specification, ovarian function, and extracellular matrix remodeling in articular cartilage. In the cardiovascular system, PCSK6 acts as a key modulator in heart formation, lipoprotein metabolism, body fluid homeostasis, cardiac repair, and vascular remodeling. To date, dysregulated PCSK6 expression or function has been implicated in major cardiovascular diseases, including atrial septal defects, hypertension, atherosclerosis, myocardial infarction, and cardiac aging. In this review, we describe biochemical characteristics and posttranslational modifications of PCSK6. Moreover, we discuss the role of PCSK6 and related molecular mechanisms in cardiovascular biology and disease.

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

Cited by 9 publications

References 28 publications

Left Ventricular Mass Index Predicts Renal Function Decline in Patients with Chronic Kidney Disease

Left Ventricular Mass Index Predicts Renal Function Decline in Patients with Chronic Kidney Disease

Proprotein Convertases and the Complement System

Proprotein Convertase Subtilisin/Kexin 6 in Cardiovascular Biology and Disease

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