School of Medical Sciences

Molecular Cardiology

Principal investigators


Our major research focus is on the molecular genetic bases of cardiovascular diseases. This includes familial hypertrophic cardiomyopathy, dilated cardiomyopathy and thrombotic factors associated with coronary heart disease. A genetic mutation occurs in the majority of cases of familial hypertrophic cardiomyopathy, whereas 20% of dilated cardiomyopathy is familial. While coronary heart disease is usually associated with abnormalities in lipid metabolism, in conjunction with smoking and or hypertension, a positive family history in the absence of these risk factors is also associated with the disorder. Thrombotic factors as possible causes of myocardial infarction are being further investigated. Also, investigations into the role of the EF-hand calcium-binding protein grancalcin in phagocytes, cells pivotal in the atherosclerotic process, are being performed.

Research Focus

Familial hypertrophic cardiomyopathy - a disorder of the sarcomere?

Hypertrophic cardiomyopathy is a disorder of myocytes characterised by unexplained cardiac hypertrophy in the absence of valvular or hypertensive heart disease. It is the major cause of sudden unexpected cardiac death in young people, and occurs between 0.1 and 1% of the population. Since 1990 six gene loci encoding sarcomere proteins involved in the contractile apparatus have been identified: á-myosin heavy changing; troponin T; …-tropomyosin; myosin binding protein C and essential and regulating myosin light chains. However these gene loci do not explain all of the familial cases. We had previously clinically characterised a large cohort of families with hypertrophic cardiomyopathy and current investigations aim to identify the molecular genetic basis of the disorder in these pedigrees.


Familial Dilated Cardiomyopathy

Dilated cardiomyopathy represents a heterogeneous disorder most commonly caused by coronary heart disease in western countries. However approximately 20% of dilated cardiomyopathy is familial, and the mode of inheritance in some families is X-linked. We have identified 2 families in which with characteristic clinical features of X-linked dilated cardiomyopathy with the disorder occurring in adolescent males with a progressive clinical deterioration over the following few years to either death or cardiac transplantation. Dystrophin has been reported as being the candidate gene in 2 families and we excluded the candidate gene, by sequencing, in one of the two families identified.


Molecular genetics and arterial thrombosis. (In collaboration with the molecular haematology group)

The major causes of coronary heart disease are lipid disorders although the event precipitating acute coronary syndromes is the development of intra-coronary thrombus. So far investigations to attempt to identify a role for genetic mutations resulting in a pro-thrombotic tendency in the pathogenesis of acute coronary syndromes, have been disappointing. We have postulated that this may be because the major risk factor for coronary heart disease is dyslipidaemia and most patients have extensive atherosclerosis. We are therefore determining whether Factor V Leiden, a mutation associated with idiopathic venus thrombosis, is present in increased frequency in young patients with coronary heart disease who on subsequent arteriography do not have evidence of severe coronary disease (i.e. there is no coronary stenosis greater than 50%).


The function of grancalcin and phagocytes

Phagocytes in particular macrophages play a major role in the pathogenesis of atherosclerosis. We have identified grancalcin, an EF-hand calcium-binding protein which becomes granule associated on cell activation. We are investigating the role of this protein in phagocyte activation. Such studies will help provide the conceptual basis for the possible development of future therapies.


Selected publications

  1. Boyhan, A., Casimir, C.M., French, J.K., Teahan, C.G., Segal, A.W. (1992). Molecular cloning and characterization of grancalcin, a novel EF-hand calcium-binding protein abundant in neutrophils and monocytes. J. Biol. Chem. 267: 2928-33.
  2. French, J.K., Cockcroft, S., Boyhan, A., Teahan, C.G., Segal, A.W. (1993). Grancalcin inhibits secretion of hexosaminidase in streptolysin-O permeabilised HL60 cells. Eur. J. Haematol. 51:330.
  3. French, J.K. Molecular cardiology: potential for diagnosis and treatment. National Heart Foundation of New Zealand, Newmarket, Auckland, New Zealand Technical Report No. 64. Auckland: October 1994.
  4. French, J.K., Van de Water, N.S., Kaye, S.D., Lander, J., Hyde, T.A., Lund, M., White, H.D., Browett, P.J. (1998). Factor V Leiden and prothrombin variant G20210A in patients <50 years with recent acute myocardial infarction and no angiographic stenosis>50%. Circulation (in press).