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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Inhibition of calcium/calmodulin (Ca2+/CaM)-Calcium/calmodulin-dependent protein kinase II (CaMKII) axis reduces in vitro and ex vivo arrhythmias in experimental Chagas disease

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Author(s):
Santos-Miranda, Artur [1] ; Costa, Alexandre D. [2] ; Joviano-Santos, V, Julliane ; Rhana, Paula [3] ; Bruno, Alexandre Santos [4] ; Rocha, Peter [3] ; Cau, Stefany Bruno [4] ; Vieira, Leda Q. [3] ; Cruz, Jader S. [3] ; Roman-Campos, Danilo [5]
Total Authors: 10
Affiliation:
[1] Univ Fed Sao Paulo, Dept Biophys, Sao Paulo - Brazil
[2] Univ Fed Minas Gerais, Dept Physiol & Biophys, Belo Horizonte, MG - Brazil
[3] Univ Fed Minas Gerais, Dept Biochem & Immunol, Belo Horizonte, MG - Brazil
[4] Univ Fed Minas Gerais, Dept Pharmacol, Belo Horizonte, MG - Brazil
[5] Joviano-Santos, Julliane, V, Univ Fed Sao Paulo, Dept Biophys, Sao Paulo - Brazil
Total Affiliations: 5
Document type: Journal article
Source: FASEB JOURNAL; v. 35, n. 10 OCT 2021.
Web of Science Citations: 0
Abstract

Chagasic cardiomyopathy (CCC) is one of the main causes of heart failure and sudden death in Latin America. To date, there is no available medication to prevent or reverse the onset of cardiac symptoms. CCC occurs in a scenario of disrupted calcium dynamics and enhanced oxidative stress, which combined, may favor the hyper activation of calcium/calmodulin (Ca2+/CaM)-calcium/calmodulin-dependent protein kinase II (CaMKII) (Ca2+/CaM-CaMKII) pathway, which is fundamental for heart physiology and it is implicated in other cardiac diseases. Here, we evaluated the association between Ca2+/CaM-CaMKII in the electro-mechanical (dys)function of the heart in the early stage of chronic experimental Trypanosoma cruzi infection. We observed that in vitro and ex vivo inhibition of Ca2+/CaM-CaMKII reversed the arrhythmic profile of isolated hearts and isolated left-ventricles cardiomyocytes. The benefits of the limited Ca2+/CaM-CaMKII activation to cardiomyocytes' electrical properties are partially related to the restoration of Ca2+ dynamics in a damaged cellular environment created after T. cruzi infection. Moreover, Ca2+/CaM-CaMKII inhibition prevented the onset of arrhythmic contractions on isolated heart preparations of chagasic mice and restored the responsiveness to the increase in the left-ventricle pre-load. Taken together, our data provide the first experimental evidence for the potential of targeting Ca2+/CaM-CaMKII pathway as a novel therapeutic target to treat CCC. (AU)

FAPESP's process: 19/21304-4 - Arrhythmogenic mechanisms in right heart diseases
Grantee:Danilo Roman Campos
Support type: Regular Research Grants
FAPESP's process: 18/20777-3 - Genetic variants of the Nav 1.5 sodium channel and its therapeutic implications.
Grantee:Julliane Vasconcelos Joviano dos Santos
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 18/22830-9 - Involvement of the Ca2+/ Calmodulin/CAMKII signaling axis in the electrical and contractile dysfunctions of the heart in the chronic phase of Chagas Disease
Grantee:Artur Santos Miranda
Support type: Scholarships in Brazil - Post-Doctorate