Remodelling of Cardiac Extracellular Matrix duringβ-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 continuousβ-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] andα1(III) [COL-III] procollagens, TGF-β1and TGF-β3mRNA 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±8μm2in vehicle-treated animals to 247±4 and 296±9μm2after 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-β1and TGF-β3increased 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±0.20v9.23±0.50% of tissue area for vehicle and ISO 7 days groups,P<0.05) and around coronary arteries (1.04±0.11v4.47±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