Willems I E, Havenith M G, Smits J F, Daemen M J
Department of Pathology, Cardiovascular Research Institute, Maastricht, The Netherlands.
Lab Invest. 1994 Jul;71(1):127-33.
Heart valves are an important denominator of the function of the heart but detailed studies of structural alterations of heart valves after hemodynamic changes are lacking.
Structural alterations of heart valves, including DNA synthesis, collagen mRNA, and protein concentration were measured in heart valves of Wistar Kyoto (WKY) rats with acute left ventricular pressure overload, created by intrarenal aortic ligation (AL, N = 18) as well as in heart valves of age-matched spontaneously hypertensive rats, a model of chronic hypertension (N = 18). SHAM aortic ligation and normal WKYs (N = 17 and N = 17) served as controls. All animals received 5'bromo-2' deoxyuridine, during the last 7 days of the experiment, in a dose of 2.4 mg/kg.day.
The cumulative labeling fraction (LF) in the mitral valve of AL animals was 47.8 +/- 5.2% as compared with 9.4 +/- 2.6% in SHAM animals (mean +/- SEM, p < 0.01). The LF in the aortic valve of AL animals was 33.3 +/- 2.9% as compared with 7.7 +/- 0.7% in SHAM animals (p < 0.01). The LF in the tricuspid valve was also significantly increased: 11.3 +/- 1.4% in AL versus 5.8 +/- 0.7% in SHAM (p < 0.01). Labeling fractions of heart valves in SHR were not increased as compared with normal WKY. The total collagen concentration in the three heart valves, measured by the hydroxyproline assay, did not change. The mRNA amounts of both collagen type I and III, detected by in situ hybridization, were increased in the heart valves of AL and spontaneously hypertensive animals as compared with the two control groups (SHAM and WKY). In all 3 heart valves, interstitial cells were vimentin-positive, but desmin-negative. A fraction of interstitial cells showed alpha-smooth muscle actin positivity. This immunophenotype did not change during pressure overload.
Heart valves have the capacity to adapt to acute pressure overload, by means of DNA synthesis and increased collagen turnover. The increase in LF in the normotensive tricuspid valve suggests a role for an additional circulating factor. A constant fraction of the interstitial heart valve cells consists of myofibroblasts.
心脏瓣膜是心脏功能的一个重要组成部分，但缺乏对血流动力学变化后心脏瓣膜结构改变的详细研究。
通过肾内主动脉结扎（AL，N = 18）在急性左心室压力过载的Wistar Kyoto（WKY）大鼠心脏瓣膜中测量心脏瓣膜的结构改变，包括DNA合成、胶原蛋白mRNA和蛋白质浓度，以及在年龄匹配的自发性高血压大鼠（慢性高血压模型，N = 18）的心脏瓣膜中进行测量。假手术主动脉结扎和正常WKY大鼠（N = 17和N = 17）作为对照。在实验的最后7天，所有动物接受剂量为2.4mg/kg·天的5'-溴-2'-脱氧尿苷。
与假手术动物的9.4±2.6%相比，AL动物二尖瓣的累积标记分数（LF）为47.8±5.2%（平均值±标准误，p < 0.01）。与假手术动物的7.7±0.7%相比，AL动物主动脉瓣的LF为33.3±2.9%（p < 0.01）。三尖瓣的LF也显著增加：AL组为11.3±1.4%，假手术组为5.8±0.7%（p < 0.01）。与正常WKY大鼠相比，SHR心脏瓣膜的标记分数没有增加。通过羟脯氨酸测定法测量的三个心脏瓣膜中的总胶原蛋白浓度没有变化。与两个对照组（假手术组和WKY大鼠）相比，通过原位杂交检测到的I型和III型胶原蛋白的mRNA量在AL和自发性高血压动物的心脏瓣膜中增加。在所有三个心脏瓣膜中，间质细胞波形蛋白呈阳性，但结蛋白呈阴性。一部分间质细胞显示α-平滑肌肌动蛋白阳性。这种免疫表型在压力过载期间没有改变。
心脏瓣膜有能力通过DNA合成和增加胶原蛋白周转来适应急性压力过载。正常血压三尖瓣中LF增加提示存在一种额外的循环因子。心脏瓣膜间质细胞的恒定比例由肌成纤维细胞组成。
