Abstract 13030: Increased Interstitial Collagen in Chronic Pressure Overload Hypertrophy is Associated with a Change in Cardiac Fibroblast Phenotype and An Increase in SPARC Expression
Background: Pressure overload (PO) causes adverse structural and functional remodeling, in particular, an increased collagen (COLL) accumulation associated with the progression to heart failure. While the pathways of COLL synthesis and degradation have been examined in PO, little is known about the critical post-synthetic processing of proCOLL to insoluble COLL. Accordingly, this study tested the hypothesis that proCOLL processing is uniquely altered in PO, and thereby is a molecular pathway that contributes to increased COLL content.
Methods and Results: A feline model of right ventricular (RV) PO was created by banding of the pulmonary artery (PAB). Total COLL was measured by hydroxyproline analysis (Hyp); collagen volume fraction (CVF) was determined histologically using picrosirius red. PAB for 2 weeks caused a significant increase in total COLL; but no increase in CVF and therefore, no increase in insoluble fibrillar COLL (Table). SPARC (secreted protein acidic and rich in cysteine) a matricellular protein vital to efficient proCOLL processing and insoluble COLL deposition was not increased 2 weeks PAB. PAB for 4 weeks caused a significant increase in total COLL, CVF and SPARC. To address cellular mechanisms of COLL deposition, quantification of COLL production by cardiac fibroblasts from normal and 4 week PAB cats was performed. RV PO fibroblasts had increased insoluble COLL, decreased soluble COLL and increased SPARC vs. normal fibroblasts. Hence, there was a phenotypic conversion in 4 week PAB fibroblasts characterized by an increased efficiency of proCOLL processing and increased insoluble COLL deposition.
Conclusions: Initial increases in COLL synthesis do not result in increased insoluble ventricular COLL until >2 weeks following initiation of PO. Increases in insoluble COLL content coincide with increased SPARC expression and a change in fibroblast phenotype. AU: Arbitrary Units, Hyp: Hydroxyproline. Data=Mean SEM; *=P<0.05 vs. control
- © 2010 by American Heart Association, Inc.