Key result
MK2 deficiency in endothelial microparticles reduced E-selectin and ICAM-1 expression, leading to reduced monocyte attachment and attenuated cardiac hypertrophy in mice.
Why the study?
This study investigated the functional significance of mitochondria in endothelial microparticles and how MAPKAPK2 governs their production and physiological effect on cardiac hypertrophy.
Does MK2 deficiency reduce EMP-mediated inflammation and cardiac hypertrophy in preclinical models?
Does MK2 deficiency reduce EMP-mediated inflammation and cardiac hypertrophy in preclinical models?
MK2 promotes the proinflammatory effect of endothelial microparticles mediated through dysfunctional mitochondria, and its deficiency attenuates cardiac hypertrophy in mice.
Should not guide clinical use of MK2 inhibition; hypothesis-generating for endothelial microparticle targeting in cardiac hypertrophy.
Objective- This study investigates the functional significance of mitochondria present in endothelial microparticles (EMP) and how MK2 (MAPKAPK2 [MAPK-activated protein kinase 2]) governs EMP production and its physiological effect on cardiac hypertrophy. Approach and Results- Flow cytometric analysis, confocal imaging, oxygen consumption rate measurement through Seahorse were used to confirm the presence of functionally active mitochondria in nontreated EMP (EMP derived from untreated control cells), lipopolysaccharide, and oligomycin treatment increased mitochondrial reactive oxygen species activity in EMP (EMP derived from cells treated with lipopolysaccharide and EMP derived from cells treated with oligomycin, respectively). The dysfunctional mitochondria contained in EMP derived from cells treated with lipopolysaccharide and EMP derived from cells treated with oligomycin induced the expression of proinflammatory mediators in the target endothelial cells leading to the augmented adhesion of human monocytic cell line on EA.hy926 cells. Multiphoton real-time imaging detected the increased adherence of EMP derived from cells treated with oligomycin at the site of carotid artery injury as compared to EMP derived from untreated control cells. MK2 regulates EMP generation during inflammation by reducing E-selectin expression and regulating the cytoskeleton rearrangement through ROCK-2 (Rho-associated coiled-coil containing protein kinase 2) pathway. MK2-deficient EMP reduced the E-selectin and ICAM-1 (intracellular adhesion molecule-1) expression on target endothelial cells leading to reduced monocyte attachment and reduced cardiac hypertrophy in mice. Conclusions- MK2 promotes the proinflammatory effect of EMP mediated through dysfunctional mitochondria. MK2 modulates the inflammatory effect induced during cardiac hypertrophy through EMP.
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Tripathi et al. (2019) studied Cardiac hypertrophy. MK2 deficiency vs. Wild-type / untreated control was evaluated on Proinflammatory effect and cardiac hypertrophy. MK2 deficiency in endothelial microparticles reduced E-selectin and ICAM-1 expression, leading to reduced monocyte attachment and attenuated cardiac hypertrophy in mice.
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