Rho-Kinase Activation in Leukocytes Plays a Pivotal Role in Myocardial Ischemia-Reperfusion InjuryReport as inadecuate

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The Rho-Rho-kinase pathway plays an important role in many cardiovascular diseases such as hypertension, atherosclerosis, heart failure, and myocardial infarction. Although previous studies have shown that Rho-kinase inhibitors reduce ischemia-reperfusion I-R injury and cytokine production, the role of Rho-kinase in leukocytes during I-R injury is not well understood. Mice were subjected to 30-min ischemia and reperfusion. Rho-kinase activity was significantly greater in leukocytes subjected to myocardial I-R compared to the sham-operated mice. Administration of fasudil, a Rho-kinase inhibitor, significantly reduced the I-R-induced expression of the proinflammatory cytokines interleukin IL-6, C-C motif chemoattractant ligand 2 CCL2, and tumor necrosis factor TNF-α, in leukocytes, compared with saline as the vehicle. Furthermore, fasudil decreased I-R-induced myocardial infarction-area at risk IA and I-R-induced leukocyte infiltration in the myocardium. Interestingly, IA in fasudil-administered mice with leukocyte depletion was similar to that in fasudil-administered mice. I-R also resulted in remarkable increases in the mRNA expression levels of the proinflammatory cytokines TNF-α, IL-6, and CCL2 in the heart. Inhibition of Rho-kinase activation in leukocytes has an important role in fasudil-induced cardioprotective effects. Hence, inhibition of Rho-kinase may be an additional therapeutic intervention for the treatment of acute coronary syndrome.

Author: Katsunori Kitano, Soichiro Usui , Hiroshi Ootsuji, Shin-ichiro Takashima, Daisuke Kobayashi, Hisayoshi Murai, Hiroshi Furusho, Ay

Source: http://plos.srce.hr/


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