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H2020Individual fellowship2017–2019

MICROS · Probing local ROS distributions in Calcium signaling microdomains after myocardial infarction

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2017-07-18 → 2019-07-17
EU contribution
€160,800
Participants
1
Scheme
MSCA-IF-EF-ST

Lines connect the coordinator with its partners.

Results in brief

Probing local ROS distributions in Calcium signaling microdomains after myocardial infarction

Context of the project: Heart and vessel diseases remain the major killer worldwide. Heart disease causes suffering and disability. It also has an important societal cost. The most common cause is disease of the blood supply to the heart causing a heart attack and a myocardial infarction (MI). After a MI, the injured heart adapts but is unable to maintain sufficient pump function to provide the necessary blood supply to the body. At the level of the heart muscle cells, this loss of pump function comes with deregulation of the calcium levels, which are the signal for contraction. The interplay of calcium and other signaling pathways, notably reactive oxygen species (ROS), is still unclear to the scientific and medical community. Insights into this signaling could contribute to the design of new strategies for treatment. Objectives: We proposed to develop a novel method for the study of local calcium release and its regulation through redox signaling in heart muscle cells. This highly challenging project had as a major conjoint objective to build new skills and competences for the researcher.

Data: CORDIS, © European Union

Project objective

An increasing number of people suffer cardiovascular diseases and experience myocardial infarction (MI). The subsequent heart remodeling is characterized by weaker contractility, hypertrophy and lethal arrhythmias. The poorly-understood underlying mechanism is related to calcium (Ca2+) mishandling in cardiomyocytes and oxidative stress. To date, most of the studies described global cellular processes and were unable to propose efficient therapies. This work will decipher the structural and functional local organization of reactive oxygen species (ROS) at Ca2+ signaling microdomains: at the vicinity of ryanodine receptors (RyR). Our knowledge is drastically hampered by the lack of local, quantitative and time-resolved ROS probes. We will thus combine the host laboratory competence in cardiac signaling and physiology, and the applicant expertise in ROS luminescent probes in order to quantify the RyR signaling domains remodeling through: (1) the measurement of local ROS production dynamics by NOX2 complexes, and (2) the imaging of the structural remodeling of the microdomains. This research will propose specific molecular targets to better diagnose and potentially reverse heart remodeling after infarction, contributing thus to solve a major public health issue in Europe. The experienced researcher (ER) will gain new technical and conceptual skills in physiology which will reinforce her multi-disciplinary profile and qualify her to lead, in a close future, her independent research activity.

Original text from CORDIS.

Participants

  • KATHOLIEKE UNIVERSITEIT LEUVEN · LeuvenCoordinatorBelgium

Links

Data: CORDIS, © European Union