Takemura G, Takatsu Y, Doyama K, Itoh H, Saito Y, Koshiji M, Ando F, Fujiwara T, Nakao K, Fujiwara H
Department of Internal Medicine, Hyogo Prefectural Amagasaki Hospital, Japan.
J Am Coll Cardiol. 1998 Mar 15;31(4):754-65. doi: 10.1016/s0735-1097(98)00045-x.
We investigated the expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and their genes in the hearts of patients with cardiac amyloidosis and those with isolated atrial amyloidosis.
The expression of ANP and BNP is augmented in the ventricles of failing or hypertrophied hearts, or both. The expression of ANP and BNP in the ventricles of hearts with cardiac amyloidosis, which is hemodynamically similar to restrictive cardiomyopathy, is not yet known. ANP is the precursor protein of isolated atrial amyloid.
We analyzed the immunohistocytochemical localizations of ANP and BNP as well as the expression of their mRNAs by in situ hybridization in the myocardium and measured the plasma levels of ANP and BNP in patients with cardiac amyloidosis.
Four of the five right and all six left ventricular endomyocardial biopsy specimens obtained from six patients with cardiac amyloidosis were immunohistochemically positive for both ANP and BNP; none of the biopsy specimens from eight normal subjects were positive for ANP or BNP. All four of the right atria obtained at operation showed positive immunoreactions for both peptides. Electron microscopy identified specific secretory granules in ventricular myocytes of the patients with cardiac amyloidosis, but not in ventricular myocytes from the normal control subjects. Double immunocytochemical analysis revealed the co-localization of ANP and BNP in the same granules and that isolated atrial amyloid fibrils were immunoreactive for ANP and BNP, whereas ventricular amyloid fibrils were negative for both peptides. Both ANP mRNA and BNP mRNA were expressed in the ventricles of the patients with cardiac amyloidosis but not in the normal ventricles. The autopsy study of four patients with cardiac amyloidosis revealed an almost transmural distribution of ANP and BNP, with predominance in the endocardial side. Plasma BNP levels in the patients were markedly elevated ([mean +/- SD] 1,165.1+/-561.2 pg/ml) compared with those in the control subjects (8.9+/-6.0 pg/ml, p < 0.05).
Expression of ANP and BNP and their genes was augmented in the ventricular myocytes of the patients with cardiac amyloidosis. Both regional mechanical stress by amyloid deposits and hemodynamic stress by diastolic dysfunction may be responsible for the expression of the peptides in patients with cardiac amyloidosis.
我们研究了心脏淀粉样变性患者和孤立性心房淀粉样变性患者心脏中利钠肽（ANP）和脑利钠肽（BNP）及其基因的表达情况。
在衰竭或肥厚的心脏心室中，或两者兼有的情况下，ANP和BNP的表达会增加。心脏淀粉样变性患者的心室中ANP和BNP的表达情况尚不清楚，心脏淀粉样变性在血流动力学上与限制型心肌病相似。ANP是孤立性心房淀粉样蛋白的前体蛋白。
我们通过免疫组织化学分析了心肌中ANP和BNP的定位，以及通过原位杂交分析了它们mRNA的表达，并测量了心脏淀粉样变性患者血浆中ANP和BNP的水平。
从6例心脏淀粉样变性患者获得的5个右心室和所有6个左心室心内膜活检标本中，有4个标本的ANP和BNP免疫组织化学染色均为阳性；8例正常受试者的活检标本中，没有一个标本的ANP或BNP呈阳性。手术中获取的所有4个右心房对这两种肽均显示阳性免疫反应。电子显微镜检查发现心脏淀粉样变性患者的心室肌细胞中有特异性分泌颗粒，而正常对照受试者的心室肌细胞中没有。双重免疫细胞化学分析显示ANP和BNP在同一颗粒中共定位，孤立的心房淀粉样纤维对ANP和BNP具有免疫反应性，而心室淀粉样纤维对这两种肽均为阴性。心脏淀粉样变性患者的心室中表达了ANP mRNA和BNP mRNA，而正常心室中未表达。对4例心脏淀粉样变性患者的尸检研究显示，ANP和BNP几乎呈透壁性分布，以内膜侧为主。与对照受试者（8.9±6.0 pg/ml，p<0.05）相比，患者的血浆BNP水平显著升高（[平均值±标准差]1,165.1±561.2 pg/ml）。
心脏淀粉样变性患者的心室肌细胞中ANP和BNP及其基因的表达增加。淀粉样沉积物引起的局部机械应力和舒张功能障碍引起的血流动力学应力可能是心脏淀粉样变性患者中这些肽表达的原因。
