TY - JOUR
T1 - P2×7 purinergic signaling in dilated cardiomyopathy induced by auto-immunity against muscarinic M 2 receptors
T2 - Autoantibody levels, heart functionality and cytokine expression
AU - Martinez, Camila Guerra
AU - Zamith-Miranda, Daniel
AU - Da Silva, Marcia Gracindo
AU - Ribeiro, Karla Consort
AU - Brandão, Izaíra Trincani
AU - Silva, Celio Lopes
AU - Diaz, Bruno Lourenço
AU - Bellio, Maria
AU - Persechini, Pedro Muanis
AU - Kurtenbach, Eleonora
N1 - Funding Information:
Sources of funding for this work were from the Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq/Doenças Negligenciadas, Fundação de Amparo a Pesquisa do Rio de Janeiro – FAPERJ/Doenças Negligenciadas and Instituto Nacional para Pesquisa Translacional em Saúde e Ambiente na Região Amazônica - INPETAM, Conselho Nacional de Desenvolvimento Científico e Tecnológico/MCT. We thank Mrs Thayane Laranja dos Anjos for conducting some ergometric adaptation protocols and Mrs Ana Paula Masson for help in immunization procedures.
PY - 2015/11/23
Y1 - 2015/11/23
N2 - Autoantibodies against the M 2 receptors (M 2 AChR) have been associated with Dilated Cardiomyopathy (DCM). In the heart, P2×7 receptors influence electrical conduction, coronary circulation and response to ischemia. They can also trigger pro-inflammatory responses and the development of neurological, cardiac and renal disorders. Here, P2×7 -/-' mice displayed an increased heart rate and ST segment depression, but similar exercise performance when compared to wild type (WT) animals. After immunization with plasmid containing M 2 AChR cDNA sequence, WT mice produced anti-M 2 AChR antibodies, while P2×7 -/-' mice showed an attenuated production. Despite this, WT and P2×7 -/-' showed left ventricle cavity enlargement and decreased exercise tolerance. Transfer of serum from M 2 AChR WT immunized mice to näive recipients led to an alteration in heart shape. P2×7 -/-' mice displayed a significant increase in the frequency of spleen regulatory T cells population, which is mainly composed by the FoxP3 + CD25- subset. M 2 AChR WT immunized mice showed an increase in IL-1β, IFNγ 3 and IL-17 levels in the heart, while P2×7 -/-' group produced lower amounts of IL-1β and IL-17 and higher amounts of IFNγ 3. These results pointed to previously unnoticed roles of P2×7 in cardiovascular and immune systems, and underscored the participation of IL-17 and IFNγ 3 in the progress of autoimmune DCM.
AB - Autoantibodies against the M 2 receptors (M 2 AChR) have been associated with Dilated Cardiomyopathy (DCM). In the heart, P2×7 receptors influence electrical conduction, coronary circulation and response to ischemia. They can also trigger pro-inflammatory responses and the development of neurological, cardiac and renal disorders. Here, P2×7 -/-' mice displayed an increased heart rate and ST segment depression, but similar exercise performance when compared to wild type (WT) animals. After immunization with plasmid containing M 2 AChR cDNA sequence, WT mice produced anti-M 2 AChR antibodies, while P2×7 -/-' mice showed an attenuated production. Despite this, WT and P2×7 -/-' showed left ventricle cavity enlargement and decreased exercise tolerance. Transfer of serum from M 2 AChR WT immunized mice to näive recipients led to an alteration in heart shape. P2×7 -/-' mice displayed a significant increase in the frequency of spleen regulatory T cells population, which is mainly composed by the FoxP3 + CD25- subset. M 2 AChR WT immunized mice showed an increase in IL-1β, IFNγ 3 and IL-17 levels in the heart, while P2×7 -/-' group produced lower amounts of IL-1β and IL-17 and higher amounts of IFNγ 3. These results pointed to previously unnoticed roles of P2×7 in cardiovascular and immune systems, and underscored the participation of IL-17 and IFNγ 3 in the progress of autoimmune DCM.
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U2 - 10.1038/srep16940
DO - 10.1038/srep16940
M3 - Article
C2 - 26592184
AN - SCOPUS:84948411923
SN - 2045-2322
VL - 5
JO - Scientific reports
JF - Scientific reports
M1 - 16940
ER -