Masson S, Arosio B, Luvarà G, Gagliano N, Fiordaliso F, Santambrogio D, Vergani C, Latini R, Annoni G
Centre for Biomedical and Pharmaceutical Research, Mario Negri Sud, Santa Maria Imbaro, Italy.
J Mol Cell Cardiol. 1998 Aug;30(8):1505-14. doi: 10.1006/jmcc.1998.0714.
Our objectives were (i) to evaluate the expression of several genes involved in the remodelling of cardiac extracellular matrix (ECM), with a special interest on SPARC (secreted protein acidic and rich in cysteine) a glycoprotein with anti-adhesive properties, and (ii) to characterise structural changes in the left (LV) and right (RV) ventricles of rats subjected to continuous beta-adrenergic stimulation. The rats were infused for 3 or 7 days with isoproterenol (ISO, 4 mg/kg/day) or vehicle. Hybridisation analysis was done for SPARC, atrial natriuretic peptide (ANP),alpha2 (I) [COL-I] and alpha1 (III) [COL-III] procollagens, TGF-beta1 and TGF-beta3 mRNA content. Interstitial and perivascular collagen deposition in both ventricles was measured after specific staining. The mean cross-sectional area of LV cardiomyocytes was evaluated by quantitative histomorphometry. ISO provoked an increase of LV mass, and a progressive enlargement of cardiomyocytes: their cross-sectional area raised from 205+/-8 micrometer2 in vehicle-treated animals to 247+/-4 and 296+/-9 micrometer2 after 3 or 7 days of ISO infusion, respectively (P<0.001). SPARC messenger abundance increased by more than 50% in LV and RV, a first evidence of its expression in the myocardium of adult rats. Transcripts of ANP, COL-III, TGF-beta1 and TGF-beta3 increased in both ventricles. COL-I transcript increased in LV (75 and 116% on days 3 and 7), but not in RV. In LV, collagen accumulated in the interstitium (2.69+/-0.20v 9. 23+/-0.50% of tissue area for vehicle and ISO 7 days groups, P<0.05) and around coronary arteries (1.04+/-0.11v 4.47+/-0.48% of lumen area for vehicle and ISO 7 days,P<0.05). Cardiac fibrosis was less marked in RV. In conclusion, early expression of SPARC, an anti-adhesive protein, and preferential expression of COL-III, a distensible form of collagen, should increase ECM plasticity and facilitate ventricular remodelling.
（i）评估参与心脏细胞外基质（ECM）重塑的几种基因的表达，特别关注具有抗黏附特性的糖蛋白富含半胱氨酸的酸性分泌蛋白（SPARC）；（ii）描述连续β-肾上腺素能刺激的大鼠左心室（LV）和右心室（RV）的结构变化。给大鼠输注异丙肾上腺素（ISO，4mg/kg/天）或赋形剂3天或7天。对SPARC、心房利钠肽（ANP）、α2（I）[I型胶原]和α1（III）[III型胶原]前胶原、转化生长因子-β1（TGF-β1）和转化生长因子-β3（TGF-β3）的mRNA含量进行杂交分析。特异性染色后测量两个心室的间质和血管周围胶原沉积。通过定量组织形态计量学评估LV心肌细胞的平均横截面积。ISO导致LV质量增加，心肌细胞逐渐增大：其横截面积在接受赋形剂处理的动物中为205±8μm²，在输注ISO 3天或7天后分别增加到247±4和296±9μm²（P<0.001）。LV和RV中SPARC信使丰度增加超过50%，这是其在成年大鼠心肌中表达的首个证据。ANP、III型胶原、TGF-β1和TGF-β3的转录本在两个心室中均增加。I型胶原转录本在LV中增加（第3天和第7天分别增加75%和116%），但在RV中未增加。在LV中，胶原在间质中积聚（赋形剂组和ISO 7天组分别为组织面积的2.69±0.20%对9.23±0.50%，P<0.05），并在冠状动脉周围积聚（赋形剂组和ISO 7天组分别为管腔面积的1.04±0.11%对4.47±0.48%，P<0.05）。RV中的心脏纤维化不太明显。总之，抗黏附蛋白SPARC的早期表达以及可扩张形式的胶原III型胶原的优先表达应会增加ECM可塑性并促进心室重塑。
