Oliviéro P, Chassagne C, Salichon N, Corbier A, Hamon G, Marotte F, Charlemagne D, Rappaport L, Samuel J L
U127 INSERM, IFR-Circulation Paris VII, Hopital Lariboisière, 41 Bd Chapelle, Université D. Diderot, 75475, Paris, France.
Cardiovasc Res. 2000 May;46(2):346-55. doi: 10.1016/s0008-6363(00)00034-1.
Fibrosis is a classical feature of cardiac hypertrophy. To date changes within the basal lamina during normal and pathological cardiac growth have been poorly investigated. The goal of the present study was to determine if the expression of the muscle specific subunit of merosin (laminin alpha2 chain) together with that of fibronectin (FN) is modified in the diseased human heart. Laminin alpha2 chain expression was also investigated during physiological and pathological cardiac growth in the rat.
In ten normal human hearts and ten hearts with idiopathic dilated cardiomyopathy (IDCM), the laminin-alpha2 and FN mRNA levels were quantified by slot-blot using total RNA and the protein distribution was analysed using an immunofluorescence approach. In Wistar rats, laminin alpha2 and FN mRNA expression was analyzed using RNase protection assay (RPA) and slot-blot assays.
The amount of laminin alpha2 mRNA did not vary in normal and pathological human hearts whereas it was significantly decreased in renovascular hypertensive rats (-20%) P<0.05 versus normal tissue). The amount of fibronectin mRNA increased in IDMC patients (x2, P<0.05 versus normal tissue), but was unchanged in hypertensive rats. A negative correlation was found between the cardiac laminin-alpha2 level and the age of the patients whatever the cardiac status. During postnatal development in the rat, a similar decrease in cardiac laminin-alpha2 level was observed between 3 and 30 weeks of age. Finally, the immunofluorescent approach failed to detect any alteration in laminin alpha2 distribution within the human myocardium.
These data indicate that an imbalance between myocyte hypertrophy and the level of laminin-alpha2 might contribute to alterations in sarcolemmal properties, which occur during the development of cardiac hypertrophy and its transition to cardiac failure.
纤维化是心脏肥大的一个典型特征。迄今为止，正常和病理性心脏生长过程中基膜内的变化尚未得到充分研究。本研究的目的是确定在患病的人类心脏中，肌纤连蛋白（层粘连蛋白α2链）与纤连蛋白（FN）的肌肉特异性亚基的表达是否发生改变。还对大鼠生理和病理性心脏生长过程中层粘连蛋白α2链的表达进行了研究。
在10个正常人类心脏和10个特发性扩张型心肌病（IDCM）心脏中，使用总RNA通过狭缝印迹法定量层粘连蛋白α2和FN的mRNA水平，并使用免疫荧光方法分析蛋白质分布。在Wistar大鼠中，使用核糖核酸酶保护分析（RPA）和狭缝印迹分析法分析层粘连蛋白α2和FN的mRNA表达。
正常和病理性人类心脏中层粘连蛋白α2 mRNA的量没有变化，而在肾血管性高血压大鼠中显著降低（-20%，与正常组织相比P<0.05）。IDMC患者中纤连蛋白mRNA的量增加（x2，与正常组织相比P<0.05），但在高血压大鼠中没有变化。无论心脏状态如何，心脏层粘连蛋白α2水平与患者年龄之间均呈负相关。在大鼠出生后的发育过程中，在3至30周龄之间观察到心脏层粘连蛋白α2水平有类似的下降。最后，免疫荧光方法未能检测到人心肌内层粘连蛋白α2分布有任何改变。
这些数据表明，心肌细胞肥大与层粘连蛋白α2水平之间的失衡可能导致肌膜特性的改变，这发生在心脏肥大发展及其向心力衰竭转变的过程中。
