The Sydney Heart Bank: improving translational research while eliminating or reducing the use of animal models of human heart disease

Abstract

The Sydney Heart Bank (SHB) is one of the largest human heart tissue banks in existence. Its mission is to provide high-quality human heart tissue for research into the molecular basis of human heart failure by working collaboratively with experts in this field. We argue that, by comparing tissues from failing human hearts with age-matched non-failing healthy donor hearts, the results will be more relevant than research using animal models, particularly if their physiology is very different from humans. Tissue from heart surgery must generally be used soon after collection or it significantly deteriorates. Freezing is an option but it raises concerns that freezing causes substantial damage at the cellular and molecular level. The SHB contains failing samples from heart transplant patients and others who provided informed consent for the use of their tissue for research. All samples are cryopreserved in liquid nitrogen within 40 min of their removal from the patient, and in less than 5-10 min in the case of coronary arteries and left ventricle samples. To date, the SHB has collected tissue from about 450 failing hearts (>15,000 samples) from patients with a wide range of etiologies as well as increasing numbers of cardiomyectomy samples from patients with hypertrophic cardiomyopathy. The Bank also has hearts from over 120 healthy This article is part of a Special Issue on 'IUPAB Edinburgh Congress' edited by Damien Hall.Electronic supplementary material The online version of this article

Protein phosphatase 5 regulates titin phosphorylation and function at a sarcomere-associated mechanosensor complex in cardiomyocytes

“…Conversely, one can test spermidine for possible inhibitory effects on PP5. These novel approaches targeting PP5 should complement other efforts in HFpEF research directed at promoting the PKs (such as PKG 54 ) that phosphorylate N2Bus and reduce cardiomyocyte passive stiffness.…”

“…Informed consent was obtained from the next of kin of all organ donors. It is a requirement of the University of Sydney Human Research Ethics Committee that the consents not only must be sighted before the heart can be included in the Sydney Heart Bank 54 , but any identifying details be redacted. Healthy dog heart tissue was obtained from adult mongrels (8–12 years) and failing heart samples from adult mongrel dogs made hypertensive by bilateral renal wrapping 55 .…”

Differences in microRNA-29 and Pro-fibrotic Gene Expression in Mouse and Human Hypertrophic Cardiomyopathy

“…Gene expression data from publicly available microarray datasets, GSE36961 (mRNA) and GSE36946 (miRNA) was downloaded from the NCBI GEO database, and analyzed for differential gene expression. The microarray datasets were obtained from ventricular septal tissue of HCM patients undergoing myectomy at the Mayo Clinic (Rochester, MN), and from age/sex-matched donor hearts (control subjects) from the Sydney Heart Bank (24,25). Information on HCM patient genotype/phenotype and control subjects was obtained from the publicly available Master's Thesis by Hebl (24).…”

Donor hearts in the Sydney Heart Bank: reliable control but is it ‘normal’ heart?

“…Cris' generosity in sharing his samples is outstanding, such that his samples have become a sort of de facto standard against which others can be measured. This has been well documented in recent publications (dos Remedios et al 2017;Lal et al 2015;Li et al 2019) Crucially, his heart bank contains a lot of donor heart material: for most researchers, this is the hardest to obtain and yet is necessary since we can only study the pathological human heart in comparison with a control, preferably a normal heart sample. Cris' donor hearts are such a control, and this review will be devoted to the studies on donor heart samples since it is not generally realised how important the control is for human heart studies.…”