The impact of SPARC on age-related cardiac dysfunction and fibrosis in Drosophila.

Vaughan, L., Marley, R., Miellet, S. and Hartley, P., 2017. The impact of SPARC on age-related cardiac dysfunction and fibrosis in Drosophila. Experimental gerontology. (In Press)

Full text available as:

[img] PDF
SPARC paper_PROOF.pdf - Accepted Version
Restricted to Repository staff only
Available under License Creative Commons Attribution Non-commercial No Derivatives.

4MB

Abstract

Tissue fibrosis, an accumulation of extracellular matrix proteins such as collagen, accompanies cardiac ageing in humans and this is linked to an increased risk of cardiac failure. The mechanisms driving age-related tissue fibrosis and cardiac dysfunction are unclear, yet clinically important. Drosophila is amenable to the study of cardiac ageing as well as collagen deposition; however it is unclear whether collagen accumulates in the ageing Drosophila heart. This work examined collagen deposition and cardiac function in ageing Drosophila, in the context of reduced expression of collagen-interacting protein SPARC (Secreted Protein Acidic and Rich in Cysteine) an evolutionarily conserved protein linked with fibrosis. Heart function was measured using high frame rate videomicroscopy. Collagen deposition was monitored using a fluorescently-tagged collagen IV reporter (encoded by the Viking gene) and staining of the cardiac collagen, Pericardin. The Drosophila heart accumulated collagen IV and Pericardin as flies aged. Associated with this was a decline in cardiac function. SPARC heterozygous flies lived longer than controls and showed little to no age-related cardiac dysfunction. As flies of both genotypes aged, cardiac levels of collagen IV (Viking) and Pericardin increased similarly. Over-expression of SPARC caused cardiomyopathy and increased Pericardin deposition. The findings demonstrate that, like humans, the Drosophila heart develops a fibrosis-like phenotype as it ages. Although having no gross impact on collagen accumulation, reduced SPARC expression extended Drosophila lifespan and cardiac health span. It is proposed that cardiac fibrosis in humans may develop due to the activation of conserved mechanisms and that SPARC may mediate cardiac ageing by mechanisms more subtle than gross accumulation of collagen.

Item Type:Article
ISSN:0531-5565
Uncontrolled Keywords:Ageing; Collagen; Fibrosis; Heart; Drosophila; SPARC
Group:Faculty of Science & Technology
ID Code:29866
Deposited By: Unnamed user with email symplectic@symplectic
Deposited On:12 Oct 2017 15:58
Last Modified:12 Oct 2017 16:05

Downloads

Downloads per month over past year

More statistics for this item...
Repository Staff Only -