Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic, MN 55905, USA.
Clin Chem. 2011 Jan;57(1):40-7. doi: 10.1373/clinchem.2010.153908. Epub 2010 Nov 12.
B-type natriuretic peptide (BNP), which is activated in heart failure (HF), is processed to an active form by corin. The corin gene is expressed in the human heart and kidney, but corin protein expression in the heart, kidney, and circulation, along with whether proBNP is processed by circulating corin, remains unknown.
We examined corin protein expression by immunostaining and Western blot in human heart and kidney, and we assessed the circulating corin concentration by ELISA. We examined histidine-tagged (His-tag) proBNP(1-108) processing in serum and plasma by immunoprecipitation and Western blot and sequenced the processed form.
Normal human heart and kidney displayed the presence of corin, especially in cells around the vasculature. Both corin and proBNP(1-108) were present in the plasma of healthy human subjects, with circulating corin significantly higher in men than women (P < 0.0001) and a positive correlation of corin to age (P = 0.0497, r = 0.27). In fresh normal plasma and serum, His-tag proBNP(1-108) was processed to a lower molecular weight form confirmed to be BNP. Processed BNP was higher in men than women (P = 0.041) and was positively correlated to plasma corin concentrations (P = 0.041, r = 0.65).
Our results support the concept that proBNP(1-108) may be processed outside of the heart in the circulation where the proprotein convertase is present. Moreover, sex may impact this process, since corin concentrations are higher in men. These findings may have important physiologic and pathophysiologic implications for the proBNP/corin system in the human.
B 型利钠肽（BNP）在心衰（HF）中被激活，被 corin 加工为活性形式。corin 基因在人体心脏和肾脏中表达，但心脏、肾脏和循环中的 corin 蛋白表达情况，以及循环 corin 是否对 proBNP 进行加工，目前尚不清楚。
我们通过免疫染色和 Western blot 检测了人心和肾中的 corin 蛋白表达情况，并通过 ELISA 检测了循环 corin 浓度。我们通过免疫沉淀和 Western blot 检测了血清和血浆中组氨酸标记的（His-tag）proBNP（1-108）的加工情况，并对加工形式进行了测序。
正常人心和肾中存在 corin，尤其是在血管周围的细胞中。健康受试者的血浆中存在 corin 和 proBNP（1-108），男性循环 corin 浓度明显高于女性（P < 0.0001），corin 与年龄呈正相关（P = 0.0497，r = 0.27）。在新鲜的正常血浆和血清中，His-tag proBNP（1-108）被加工为分子量较低的 BNP 形式。男性的加工型 BNP 高于女性（P = 0.041），且与血浆 corin 浓度呈正相关（P = 0.041，r = 0.65）。
我们的研究结果支持 proBNP（1-108）可能在循环系统中被加工为活性形式的观点，而循环系统中存在蛋白原转化酶。此外，性别可能影响这一过程，因为男性的 corin 浓度更高。这些发现可能对人体 proBNP/corin 系统具有重要的生理和病理生理意义。
