Key result
Immunization with M2AChR plasmid induced left ventricle cavity enlargement and decreased exercise tolerance in both wild type and P2x7 knockout mice, despite the knockout mice showing attenuated autoantibody production.
p-value: p=<0.05
P2X7 receptors modulate the immune response and cytokine profile in autoimmune dilated cardiomyopathy, though their deficiency does not prevent cardiac dilation and exercise intolerance.
P2X7 knockout attenuates autoantibodies but not M2AChR-induced LV dilation or exercise intolerance in mice; leaves open its value as a therapeutic target.
Autoantibodies against the M2 receptors (M2AChR) 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 M2AChR cDNA sequence, WT mice produced anti-M2AChR 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 M2AChR 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. M2AChR WT immunized mice showed an increase in IL-1β, IFNγ 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. These results pointed to previously unnoticed roles of P2×7 in cardiovascular and immune systems, and underscored the participation of IL-17 and IFNγ in the progress of autoimmune DCM.
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Martinez et al. (2015) studied Dilated cardiomyopathy (n=40). Immunization with pcDNA3-hM2 plasmid vs. Immunization with empty pcDNA3 plasmid was evaluated on Left ventricle cavity enlargement and exercise tolerance (p=<0.05). Immunization with M2AChR plasmid induced left ventricle cavity enlargement and decreased exercise tolerance in both wild type and P2x7 knockout mice, despite the knockout mice showing attenuated autoantibody production.
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