Cardiac 

Mechanics

"Understanding how heart
cells respond to increased
workloads is critical to
preventing heart failure,"

- Professor Michael Feneley

Professor Michael Feneley 

Head, Cardiac Mechanics Laboratory 

Research Overview

Key Research Areas

  • Cardiomyopathy
  • Congenital Heart disease 
  • Ischemic heart disease

Research Overview 

For over a decade researchers in the Cardiac Mechanics Laboratory directed by Prof Michael Feneley have studied how heart cells grow in disease and how effectively the heart contracts and relaxes under these conditions. The team is trying to understand the genetic and biochemical processes of cardiac hypertrophy. Cardiac hypertrophy happens naturally in pregnancy and with exercise, but untreated abnormal enlargement of the heart muscle often leads to heart failure. Chronic high blood pressure is the most common factor leading to cardiac hypertrophy and is due to lifestyle, diet, genetics or interplay between these. In 2018 Professor Chris Hayward will take on the leadership of the laboratory and although the current focus will continue additional research into heart assist devices will be undertaken. Heart failure often results in heart transplantation and assist devices maybe used in that setting. Heart failure has an enormous social cost and the economic burden on our healthcare system is substantial as patients often suffer an increasing number of illnesses and need rising rates of hospital care. 

research projects

The Cardiovascular Mechanics Program includes a small animal physiology core laboratory, and a clinical research program. There are 5 key projects underway in the Cardiac Mechanics Laboratory, led by Professor Michael Feneley; 

1. Chronicling the patterns of cell growth and population increases in early development in mice that are either normal or model congenital human heart disease known to manifest only after the adolescent growth spurt.

2. Demonstration that calcineurin activation plays a role in the induction of left ventricular hypertrophy in response to increased afterload only when the systemic renin-angiotensin system is activate.

3. With Diane Fatkin on a collaborative study of zebrafish hearts as models of human heart disease caused by mutations in Titin, a very large protein that is integral to the contractile apparatus of heart cells. This work is made possible following the establishment of methods for the use of high frequency ultrasound in zebrafish by PhD student Dr Louis Wang.

4. Determining the existence and role of an adrenergic receptor (AR), the 1D-AR receptor in the muscle cells of the heart previously thought not to be present. Whole heart work so far indicates its existence and an interaction with another AR the 2, which is targeted by many hypertension drugs due to its dominant role in controlling blood pressure.

5. With Prof Boris Martinac several studies are being undertaken examining the connection between mechanical stretch receptors found on the surface of heart cells and the triggering of the biochemical and genetic cascade leading to hypertrophy. Several candidate receptors including TRPC’s, TRPM’s and most recently Peizo are being characterised in various models of human condition which lead to hypertrophy.

Laboratory members

Laboratory Members

Jane Yu, Senior Staff Scientist 

Yang Guo, Research Assistant 

Scott Kesteven, Senior Research Officer 

publication highlights

1. Standardized echocardiographic assessment of cardiac function in normal adult zebrafish and heart disease models. Wang LW, Huttner IG, Santiago CF, Kesteven SH, Yu ZY, Feneley MP, Fatkin D. Dis Model Mech. 2017 Jan 1;10(1):63-76. 

2. Pressure Overload by Transverse Aortic Constriction Induces Maladaptive Hypertrophy in a Titin-Truncated Mouse Model. Zhou Q, Kesteven S, Wu J, Aidery P, Gawaz M, Gramlich M, Feneley MP, Harvey RP. Biomed Res Int. 2015;2015:163564. 

3. Snowflakes in the heart: an ultrasonic marker of severe hypercoagulability. Wang LW, Grygiel JJ, O'Neill JH, Fatkin D, Feneley MP. Lancet. 2015 Jan 17;385(9964):302. 

4. Irreversible triggers for hypertrophic cardiomyopathy are established in the early postnatal period. Cannon L, Yu ZY, Marciniec T, Waardenberg AJ, Iismaa SE, Nikolova-Krstevski V, Neist E, Ohanian M, Qiu MR, Rainer S, Harvey RP, Feneley MP, Graham RM, Fatkin D.J Am Coll Cardiol. 2015 Feb 17;65(6):560-9.

5. RhoA/ROCK signaling and pleiotropic α1A-adrenergic receptor regulation of cardiac contractility. Yu ZY, Tan JC, McMahon AC, Iismaa SE, Xiao XH, Kesteven SH, Reichelt ME, Mohl MC, Smith NJ, Fatkin D, Allen D, Head SI, Graham RM, Feneley MP. PLoS One. 2014 Jun 11;9(6):e99024. 

6. Granulocyte colony stimulating factor in chronic angina to stimulate neovascularisation: a placebo controlled crossover trial. Chih S, Macdonald PS, McCrohon JA, Ma D, Moore J, Feneley MP, Law M, Kovacic JC, Graham RM. Heart. 2012 Feb;98(4):282-90. 

7. Liew GY, Feneley MP, Worthley SG. Appropriate indications for computed tomography coronary angiography. Med J Aust. 2012 Mar 5;196(4):246-9. Review.

8. Chih S, Macdonald PS, McCrohon JA, Ma D, Moore J, Feneley MP, Law M, Kovacic JC, Graham RM. Granulocyte colony stimulating factor in chronic angina to stimulate neovascularisation: a placebo controlled crossover trial. Heart. 2012 Feb;98(4):282-90.

9. Granados-Riveron JT, Pope M, Bu’lock FA, Thornborough C, Eason J, Setchfield K, Ketley A, Kirk EP, Fatkin D, Feneley MP, Harvey RP, Brook JD. Combined mutation screening of NKX2-5, GATA4, and TBX5 in congenital heart disease: multiple heterozygosity and novel mutations. Congenit Heart Dis. 2012 Mar-Apr;7(2):151-9. doi: 10.1111/j.1747-0803.2011.00573.x.

10. Yeoh T, Hayward C, Benson V, Sheu A, Richmond Z, Feneley MP, Keogh AM, Macdonald P, Fatkin D. A randomised, placebo-controlled trial of carvedilol in early familial dilated cardiomyopathy. Heart Lung Circ. 2011 Sep;20(9):566-73.

11. Moradi Marjaneh M, Kirk EP, Posch MG, Ozcelik C, Berger F, Hetzer R, Otway R,  Butler TL, Blue GM, Griffiths LR, Fatkin D, Martinson JJ, Winlaw DS, Feneley MP,  Harvey RP. Investigation of association between PFO complicated by cryptogenic stroke and a common variant of the cardiac transcription factor GATA4. PLoS One.  2011;6(6):e20711.

12. Fatkin D, Yeoh T, Hayward CS, Benson V, Sheu A, Richmond Z, Feneley MP, Keogh  AM, Macdonald PS. Evaluation of left ventricular enlargement as a marker of early disease in familial dilated cardiomyopathy. Circ Cardiovasc Genet. 2011 Aug 1;4(4):342-8.

13. Nikolova-Krstevski V, Leimena C, Xiao XH, Kesteven S, Tan JC, Yeo LS, Yu ZY, Zhang Q, Carlton A, Head S, Shanahan C, Feneley MP, Fatkin D. Nesprin-1 and actin contribute to nuclear and cytoskeletal defects in lamin A/C-deficient cardiomyopathy. J Mol Cell Cardiol. 2011 Mar;50(3):479-86.

14. Chih S, Macdonald PS, Feneley MP, Law M, Graham RM, McCrohon JA. Reproducibility of adenosine stress cardiovascular magnetic resonance in multi-vessel symptomatic coronary artery disease. J Cardiovasc Magn Reson. 2010 Jul 21;12:42.

15. Granados-Riveron JT, Ghosh TK, Pope M, Bu’Lock F, Thornborough C, Eason J, Kirk EP, Fatkin D, Feneley MP, Harvey RP, Armour JA, David Brook J. Alpha-cardiac myosin heavy chain (MYH6) mutations affecting myofibril formation are associated  with congenital heart defects. Hum Mol Genet. 2010 Oct 15;19(20):4007-16.

16. Lai D, Liu X, Forrai A, Wolstein O, Michalicek J, Ahmed I, Garratt AN, Birchmeier C, Zhou M, Hartley L, Robb L, Feneley MP, Fatkin D, Harvey RP. Neuregulin 1 sustains the gene regulatory network in both trabecular and nontrabecular myocardium. Circ Res. 2010 Sep 17;107(6):715-27.

17. Chandar S, Yeo LS, Leimena C, Tan JC, Xiao XH, Nikolova-Krstevski V, Yasuoka  Y, Gardiner-Garden M, Wu J, Kesteven S, Karlsdotter L, Natarajan S, Carlton A, Rainer S, Feneley MP, Fatkin D. Effects of mechanical stress and carvedilol in lamin A/C-deficient dilated cardiomyopathy. Circ Res. 2010 Feb 19;106(3):573-82.

18. Hing AJ, Watson A, Hicks M, Gao L, Faddy SC, McMahon AC, Kesteven SH, Wilson  MK, Jansz P, Feneley MP, Macdonald PS. Combining cariporide with glyceryl trinitrate optimizes cardiac preservation during porcine heart transplantation. Am J Transplant. 2009 Sep;9(9):2048-56.

19. Kovacic JC, Macdonald P, Feneley MP, Graham RM. Granulocyte-colony stimulating factor in refractory ischemic heart disease: throwing stones from glass houses. Am Heart J. 2009 May;157(5):e39; author reply e41.

20. Kovacic JC, Macdonald P, Feneley MP, Muller DW, Freund J, Dodds A, Milliken S, Tao H, Itescu S, Moore J, Ma D, Graham RM. Safety and efficacy of consecutive  cycles of granulocyte-colony stimulating factor, and an intracoronary CD133+ cell infusion in patients with chronic refractory ischemic heart disease: the G-CSF in angina patients with IHD to stimulate neovascularization (GAIN I) trial. Am Heart J. 2008 Nov;156(5):954-63. 

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