Dissecting the role of the extracellular matrix in heart disease: Lessons from the Drosophila genetic model

19Citations
Citations of this article
74Readers
Mendeley users who have this article in their library.

Abstract

The extracellular matrix (ECM) is a dynamic scaffold within organs and tissues that enables cell morphogenesis and provides structural support. Changes in the composition and organisation of the cardiac ECM are required for normal development. Congenital and age-related cardiac diseases can arise from mis-regulation of structural ECM proteins (Collagen, Laminin) or their receptors (Integrin). Key regulators of ECM turnover include matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of matrix metalloproteinases (TIMPs). MMP expression is increased in mice, pigs, and dogs with cardiomyopathy. The complexity and longevity of vertebrate animals makes a short-lived, genetically tractable model organism, such as Drosophila melanogaster, an attractive candidate for study. We survey ECM macromolecules and their role in heart development and growth, which are conserved between Drosophila and vertebrates, with focus upon the consequences of altered expression or distribution. The Drosophila heart resembles that of vertebrates during early development, and is amenable to in vivo analysis. Experimental manipulation of gene function in a tissue- or temporally-regulated manner can reveal the function of adhesion or ECM genes in the heart. Perturbation of the function of ECM proteins, or of the MMPs that facilitate ECM remodelling, induces cardiomyopathies in Drosophila, including cardiodilation, arrhythmia, and cardia bifida, that provide mechanistic insight into cardiac disease in mammals.

Cite

CITATION STYLE

APA

Hughes, C. J. R., & Jacobs, J. R. (2017, June 1). Dissecting the role of the extracellular matrix in heart disease: Lessons from the Drosophila genetic model. Veterinary Sciences. MDPI Multidisciplinary Digital Publishing Institute. https://doi.org/10.3390/vetsci4020024

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free