TY - JOUR
T1 - Measuring passive myocardial stiffness in Drosophila melanogaster to investigate diastolic dysfunction
AU - Kaushik, Gaurav
AU - Zambon, Alexander C.
AU - Fuhrmann, Alexander
AU - Bernstein, Sanford I.
AU - Bodmer, Rolf
AU - Engler, Adam J.
AU - Cammarato, Anthony
PY - 2012/8
Y1 - 2012/8
N2 - Aging is marked by a decline in LV diastolic function, which encompasses abnormalities in diastolic relaxation, chamber filling and/or passive myocardial stiffness. Genetic tractability and short life span make Drosophila melanogaster an ideal organism to study the effects of aging on heart function, including senescent-associated changes in gene expression and in passive myocardial stiffness. However, use of the Drosophila heart tube to probe deterioration of diastolic performance is subject to at least two challenges: the extent of genetic homology to mammals and the ability to resolve mechanical properties of the bilayered fly heart, which consists of a ventral muscle layer that covers the contractile cardiomyocytes. Here, we argue for widespread use of Drosophila as a novel myocardial aging model by (1) describing diastolic dysfunction in flies, (2) discussing how critical pathways involved in dysfunction are conserved across species and (3) demonstrating the advantage of an atomic force microscopy-based analysis method to measure stiffness of the multilayered Drosophila heart tube versus isolated myocytes from other model systems. By using powerful Drosophila genetic tools, we aim to efficiently alter changes observed in factors that contribute to diastolic dysfunction to understand how one might improve diastolic performance at advanced ages in humans.
AB - Aging is marked by a decline in LV diastolic function, which encompasses abnormalities in diastolic relaxation, chamber filling and/or passive myocardial stiffness. Genetic tractability and short life span make Drosophila melanogaster an ideal organism to study the effects of aging on heart function, including senescent-associated changes in gene expression and in passive myocardial stiffness. However, use of the Drosophila heart tube to probe deterioration of diastolic performance is subject to at least two challenges: the extent of genetic homology to mammals and the ability to resolve mechanical properties of the bilayered fly heart, which consists of a ventral muscle layer that covers the contractile cardiomyocytes. Here, we argue for widespread use of Drosophila as a novel myocardial aging model by (1) describing diastolic dysfunction in flies, (2) discussing how critical pathways involved in dysfunction are conserved across species and (3) demonstrating the advantage of an atomic force microscopy-based analysis method to measure stiffness of the multilayered Drosophila heart tube versus isolated myocytes from other model systems. By using powerful Drosophila genetic tools, we aim to efficiently alter changes observed in factors that contribute to diastolic dysfunction to understand how one might improve diastolic performance at advanced ages in humans.
KW - Aging
KW - Atomic force microscopy
KW - Diastolic dysfunction
KW - Drosophila
KW - Heart
KW - Myocardial stiffness
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U2 - 10.1111/j.1582-4934.2011.01517.x
DO - 10.1111/j.1582-4934.2011.01517.x
M3 - Article
C2 - 22225769
AN - SCOPUS:84864378848
SN - 1582-1838
VL - 16
SP - 1656
EP - 1662
JO - Journal of Cellular and Molecular Medicine
JF - Journal of Cellular and Molecular Medicine
IS - 8
ER -