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T
he prevalence of Metabolic Syndrome (MS) in Mexico has increased in the last 10 years. MS is a serious health problem due
to its related cardiovascular disorders, such as hypertension and heart failure. The latter is among the major causes of death
in Mexico; however, the molecular mechanisms responsible for cardiac dysfunction in MS patients are unclear and could be
related to anomalies in the cardiac excitation-contraction coupling (E-C coupling). The cardiac Ryanodine Receptor (RyR2) is
a macromolecular complex that participates in releasing Ca
2+
from internal stores and is involved in E-C coupling. Our aim has
been to examine alterations at the expression level, phosphorylation status, Ca
2+
sensitivity and
in situ
function (Ca
2+
sparks and
Ca
2+
transients) of RyR2 that could explain the cardiac dysfunction associated with MS.
In an experimental model of MS we found that cardiomyocytes displayed diminished intracellular Ca
2+
transients with
impaired cell contractility and decrease in Ca
2+
spark frequency. [3H] Ryanodine binding showed that functional RyR2
are decreased in MS hearts with no changes of its Ca
2+
sensitivity. However MS did not alter the phosphorylation of RyR2
at serine-2809 linked to the development of heart failure due to leaky RyR2. Then, the impaired RyR2 functionality could be
attributable to additional stress-induced RyR2 modifications but not to changes at RyR2 phosphorylation status. RyR2 alterations
may account for the poor overall cardiac outcome found in MS patients and could be targeting for future therapies.
Biography
Angelica Rueda is Professor at the Department of Biochemistry, Cinvestav-IPN, Mexico, since 2008. She was a fellow of the AHA during her
postdoctoral stay at the Department of Physiology, Medical School, University of Wisconsin-Madison. In 2006 she moved to Ana Maria Gomez
Laboratory (Montpellier France) to study calcium handling alterations in vascular smooth muscle cells from the diabetic db/db mice. She has 17
publications, one book chapter, and is part of the National System of Researchers in Mexico. In 2010, she was awarded with Dr. Jorge Rosenkranz
prize from Roche of Mexico, in the area of diabetes.
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