Remodelling of cardiac extracellular matrix during β-adrenergic stimulation: Upregulation of SPARC in the myocardium of adult rats

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 β-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), α₂ (I) [COL-I] and α₁ (III) [COL-III] procollagens, TGF-β₁ and TGF-β₃ 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 μm² in vehicle-treated animals to 247 ± 4 and 296 ± 9 μm² 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-β₁ and TGF-β₃ 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 ± 0.20 v 9.23 ± 0.50% of tissue area for vehicle and ISO 7 days groups, P <0.05) and around coronary arteries (1.04 ± 0.11 v 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.