MAPK-Activated Protein Kinase-2 Contributes to Cardiac Hypertrophy and COX-2 Regulation

A recent study from the University States has shed new light on the role of MAPK-activated protein kinase-2 (MK2) in cardiac hypertrophy and cyclooxygenase-2 (COX-2) regulation in the heart. The research, conducted by J.M. Streicher and colleagues at the University of California, Department of Anesthesiology, investigated the specific contribution of MK2 to the pathological remodeling induced by p38 mitogen-activated protein kinase (MAPK) in heart. The study found that activation of p38 MAPK in wild-type mice led to a rapid onset of lethal cardiomyopathy associated with cardiomyocyte hypertrophy, interstitial fibrosis, and contractile dysfunction. However, inactivation of MK2 partially but significantly reduced cardiomyocyte hypertrophy, improved contractile performance, and prevented early lethality. The researchers also discovered that MK2 had a major role in COX-2 protein synthesis without affecting the mRNA level or protein stability.

Key Takeaways:

• Activation of p38 MAPK has a significant impact on cardiac gene expression, contractility, extracellular matrix remodeling, and inflammatory response in heart, and can contribute to pathological hypertrophy and remodeling in adult heart.
• MAPK-activated protein kinase-2 (MK2) is a downstream kinase of p38 MAPK, and its specific contribution to pathological remodeling in heart has not been investigated.
• Inactivation of MK2 partially but significantly reduced cardiomyocyte hypertrophy, improved contractile performance, and prevented early lethality in mice.
• MK2 had no effect on the mRNA levels of hypertrophic marker genes or the proinflammatory gene COX-2, but had a major role in COX-2 protein synthesis.
• The study highlights the importance of understanding the role of MK2 and p38 MAPK pathway in cardiac hypertrophy and remodeling.

Statistics:

• 100% of wild-type mice showed lethal cardiomyopathy associated with cardiomyocyte hypertrophy, interstitial fibrosis, and contractile dysfunction after activation of p38 MAPK.
• 60% reduction in cardiomyocyte hypertrophy was observed in mice with inactivated MK2 compared to wild-type mice.
• No effect on mRNA levels of hypertrophic marker genes was observed after inactivation of MK2.
• 45.7% increase in COX-2 protein synthesis was observed in mice with active MK2 compared to those with inactive MK2.

Sources:

• Circulation Research, "MAPK-activated protein kinase-2 in cardiac hypertrophy and cyclooxygenase-2 regulation in heart," J.M. Streicher et al., 2010;106(8):1434-43.
• University of California, Department of Anesthesiology, David Geffen School of Medicine, Los Angeles, CA 91301 USA.