Metabolomics of cardiac adaptation to hemodynamic conditions at early embryonic stages
EMSL Project ID
47777
Abstract
Cardiovascular development is the result of intrinsic genetic programs modulated by hemodynamic conditions. Using animal models of heart development, it has been shown that hemodynamic conditions are essential for proper heart development, and that altered blood flow conditions lead to congenital heart malformation. While mechanotransduction effects are likely responsible for the adaptations of the developing heart to altered hemodynamic conditions, the exact mechanisms by which this occurs, and the early adaptation events that take place, are less well understood. In this project we propose to study metabolic embryonic cardiac tissue adaptations to hemodynamic conditions using a chick model of cardiac development. In particular we will focus on early metabolic adaptations (within 48hrs) in the early chick tubular heart that will later lead to cardiac malformations. Our previous studies showed that after hemodynamic interventions that increase intracardiac pressure, and locally alter mechanical stimuli (stresses and strains), collagen and proteoglycan constituents in the developing heart increase in a localized manner. These findings suggest that the heart tissue remodels in response to local mechanical cues, giving rise to localized adaptations. It is therefore likely that the abundance of smaller metabolite molecules in the cardiac wall also changes in response to altered hemodynamic conditions. This adaptation, however, has not been studied before. We propose using mass-spectrometry techniques available at EMSL, together with the expertise of Dr. Pasa-Tolic and Dr. Laskin, to unravel early metabolic adaptations to altered hemodynamic conditions during embryonic development. More specifically, we will use nano-DESI and MALDI-FTMS to image the metabolic adaptations of normal (control) developing hearts versus hearts in which hemodynamic conditions have been altered (n=3 each). We request rapid access, because we would like to gather preliminary data to submit a proposal to the recent FOA “Collaborative Activities to Promote Metabolomics Research (Admin Supp)”, PA-13-041, with a due date of March 15, 2013.
Project Details
Project type
Limited Scope
Start Date
2013-02-20
End Date
2013-04-22
Status
Closed
Released Data Link
Team
Principal Investigator