Biochem Soc Trans. 2016 Oct 15;44(5):1549-1560.

Can the Drosophila model help in paving the way for translational medicine in heart failure?

Lisha Ma (lishamaw@gmail.com)

Bournemouth University, Bournemouth, U.K.

 

Abstract

Chronic heart failure is a common consequence of various heart diseases. Mechanical force is known to play a key role in heart failure development through regulating cardiomyocyte hypertrophy. In order to understand the complex disease mechanism, this article discussed a multi-disciplinary approach that may aid the illustration of heart failure molecular process.

PubMed

 

Summary

In my review paper (1) as title above, I discussed the limitations on gaining understanding about the complex molecular mechanisms of heart disease development, in particular heart failure, by using mammalian research systems alone. Based on comparisons between the mammalian and the simple fruit fly (Drosophila melanogaster) systems, I described in the paper how the fly system may help to circumvent current difficulties in mammalian heart studies towards better understanding of the health problems of the heart. Relevant references in the following paragraphs may be sourced in my review paper.

 

A healthy heart can comfortably support various body activities in our daily life regardless of their oxygen consumption rate, so that our body may effectively rest or when needed, sprint to catch a bus for example. The heart wall may even be strengthened by increasing its thickness through physical training, as seen in athletes. The increase in thickness of the heart wall as a result from these types of physical training is known as cardiac adaptation. However, the adaptability of the heart is apparently not unlimited. Failing to adapt its capacity to suit one’s particular life activities may trigger heart disease and eventually (chronic) heart failure.

 

The structural basis of a failing heart is associated with its progressively increased areas of myofibers becoming damaged or disappearing. Integrin adhesomes, multi-protein structures at the cell membrane, can sense the change in mechanical forces in the heart and recruit muscle filaments. Therefore, learning how forces regulate the function of integrin adhesomes is important for understanding how the heart adapts and why it can become diseased. In studies with mammalian hearts, there are practical difficulties in gaining accurate dynamical details on the functions of individual genes or molecules in heart disease development. This is because mammalian systems generally have low accessibility in their living conditions.

Reduction of cardiac expression of the integrin gene in failing hearts with myofiber losses is seen in both mammalian and fly hearts, indicating a conserved function of integrins and adhesomes in the fruit fly. With its high accessibility through the body surface at certain fly development stages and the structural associated simple force pattern (see the Diagram), the fly heart presents an attractive in vivo model to study the force regulation of cardiac adaptation. Based on the aspects of differences and similarities between the two species (see the Table), it is feasible to use fly heart data as reference to correlate ex vivo mammalian heart cell studies with specific health states of the heart.

 

Table: differences and similarities between mammalian and fruit fly hearts.

 

In my paper (1), I, therefore, proposed a three-part approach to study heart failure: 1) Establish (semi-)quantitative knowledge of the fruit fly heart; 2) Use fruit fly data to aid the correlation of ex vivoin vivo mammalian studies; 3) Computationally analyze multiple genes of the fly heart to aid translational studies of heart disease processes.

 

Reference: 

  1. Ma L. (2016) Can the Drosophila model help in paving the way for translational medicine in heart failure? Biochemical Society Transactions 44:1549-1560.