利钠肽家族是一组由心肌细胞分泌的激素, 主要包括A型、B型和C型利钠肽, 具有相似的基因结构和生理学效应, 可对心血管系统产生血压调节、抗心肌肥厚、抗心肌纤维化和抗心肌弛缓等保护作用。利钠肽受体A、B和C亦介导多种生理活性, 调节心血管稳态。利钠肽受体A选择性结合A型、B型利钠肽。利钠肽受体B结合C型利钠肽。利钠肽受体C结合各型利钠肽, 通过受体介导的内化和退化作用清除血液循环中利钠肽。对利钠肽家族及其受体基因单核甘酸多态性及功能研究显示, 其与多种心血管疾病(房颤、高血压、心力衰竭等)的易感性相关。利钠肽家族及其受体基因缺失的转基因小鼠表现为心肌肥厚、心肌纤维化, 与高血压、心肌病及心力衰竭的发生发展相关。各种导致心肌肥厚和缺血性损伤的刺激均参与利钠肽及其受体基因的表达调控。临床将脑钠肽作为左室功能障碍和心力衰竭失代偿的一个预测指标。静脉注射重组脑钠肽已经成为治疗急性心力衰竭的有效手段。深入了解利钠肽家族基因变异及其信号调控有助于探索心血管疾病的病理生理机制, 为临床诊疗开辟新思路。
Natriuretic peptide family consists of several hormones produced by cardiomyocyte, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP). They possess similar gene structures and protective effects of cardiovascular physiology, such as anti-hypertrophy, anti-fibrosis, myocardial relaxation and blood pressure regulation. The corresponding natriuretic peptide receptor A, B and C mediate multiple effects of natriuretic peptides to maintain cardiovascular homeostasis. Specially, natriuretic peptide receptor-A preferentially binds ANP and BNP, while natriuretic peptide receptor-B is more selective for C-type natriuretic peptides. Natriuretic peptide recep-tor-C(NPR-C), binding all kinds of natriuretic peptides, clears natriuretic peptides from the circulation through recep-tor-mediated internalization and degradation. BNP levels were reported to be a good predictor of left ventricular dysfunc-tion and decompensated heart failure from a clinical standpoint. BNP infusion is an effective treatment for acute heart fail-ure. Investigations on natriuretic peptides’ single nucleotide polymorphisms and biological function suggested that they could be associated with several cardiovascular diseases, such as atrial fibrillation, cardiomyopathy, heart failure and so on. Transgenic mice with natriuretic peptides and their receptors gene deletion display myocardial hypertrophy and fibrosis, which are associated with the development of hypertension, cardiomyopathy and heart failure. Certain stimuli triggering cardiac hypertrophy and ischemic injuries may be involved in regulating gene expression of natriuretic peptides and their receptors. Therefore, advances in understanding of natriuretic peptide family genes and their regulatory mechanisms will lead to greater insight into the pathogenesis of cardiovascular diseases and blaze a new trail in clinical treatment.
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