Mitogen-activated protein kinase signaling in the heart: angels versus demons in a heart-breaking tale
Beth A Rose1, Thomas Force, Yibin Wang
1Departments of Anesthesiology, Physiology, and Medicine, David Geffen School of Medicine, Molecular Biology, Institute, University of California at Los Angeles, Los Angeles, CA 90095, USA.
Abstract:
Among the myriad of intracellular signaling networks that govern the cardiac development and pathogenesis, mitogen-activated protein kinases (MAPKs) are prominent players that have been the focus of extensive investigations in the past decades. The four best characterized MAPK subfamilies, ERK1/2, JNK, p38, and ERK5, are the targets of pharmacological and genetic manipulations to uncover their roles in cardiac development, function, and diseases. However, information reported in the literature from these efforts has not yet resulted in a clear view about the roles of specific MAPK pathways in heart. Rather, controversies from contradictive results have led to a perception that MAPKs are ambiguous characters in heart with both protective and detrimental effects. The primary object of this review is to provide a comprehensive overview of the current progress, in an effort to highlight the areas where consensus is established verses the ones where controversy remains. MAPKs in cardiac development, cardiac hypertrophy, ischemia/reperfusion injury, and pathological remodeling are the main focuses of this review as these represent the most critical issues for evaluating MAPKs as viable targets of therapeutic development. The studies presented in this review will help to reveal the major challenges in the field and the limitations of current approaches and point to a critical need in future studies to gain better understanding of the fundamental mechanisms of MAPK function and regulation in the heart.
Insights
Mitogen-activated protein kinases (MAPKs) have complex roles in heart development and disease, with research showing both protective and harmful effects. Further study is needed to clarify their mechanisms and therapeutic potential.
Area of Science:
- Cardiovascular Biology
- Molecular Signaling
- Cellular Pathophysiology
Background:
- Mitogen-activated protein kinases (MAPKs) are crucial intracellular signaling molecules involved in cardiac development and disease.
- Key MAPK pathways (ERK1/2, JNK, p38, ERK5) have been extensively studied but yield conflicting results regarding their cardiac functions.
- The dual protective and detrimental roles of MAPKs in the heart create ambiguity in their therapeutic targeting.
Purpose of the Study:
- To provide a comprehensive review of current research on MAPK roles in the heart.
- To distinguish established consensus from ongoing controversies regarding MAPK functions.
- To evaluate MAPKs as potential therapeutic targets for cardiac conditions.
Main Methods:
- Literature review and synthesis of existing research findings.
- Analysis of studies investigating MAPKs in cardiac development, hypertrophy, ischemia/reperfusion injury, and pathological remodeling.
- Identification of challenges and limitations in current MAPK research approaches.
Main Results:
- Significant controversies exist regarding the specific roles of MAPK pathways in cardiac function and disease.
- MAPK pathways exhibit both beneficial and detrimental effects, complicating therapeutic strategies.
- Current research highlights the need for a deeper understanding of MAPK mechanisms in the heart.
Conclusions:
- Consensus on MAPK functions in the heart remains elusive due to contradictory findings.
- Understanding MAPK regulation is critical for developing effective cardiac therapies.
- Future research should focus on elucidating fundamental MAPK mechanisms in cardiac pathophysiology.
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