SPARC mediates cardiac ageing

Authors: Hartley, P.S.

Start date: 28 April 2015

Collagen deposition is crucial for normal development but also contributes to tissue fibrosis and promotes pathological organ dysfunction in ageing and disease. SPARC (Secreted Protein Acidic and Rich in Cysteine) is a collagen binding matricellular protein and attractive anti-fibrotic target. Studying SPARC in mammalian models is challenging and limited by ethical, technical and financial constraints. Here we examined whether SPARC may play a role in cardiac ageing using the fruit fly Drosophila. Collagen deposition was assessed using Picrosirius red and fluorescently tagged collagen IV. Collagen was most pronounced around the heart, especially at the valves and distal heart region. Collagen deposition increased significantly as flies aged, despite reduced expression of two collagen-IV genes and SPARC. These changes correlated with the well-documented age-related decline of cardiac function, characterised by a slower heart rate, longer diastolic and systolic intervals and increased arrhythmia. Importantly, flies heterozygous for a loss-of-function SPARC allele, exhibited normal cardiac development but reduced collagen deposition in ageing and no age-related decline in cardiac function. These findings parallel those from mammalian models and highlight Drosophila as a novel system with which to study the impact of SPARC on age-related collagen deposition and cardiac dysfunction.

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