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Published on: October 25, 2024
Role of p38 MAPK in Atherosclerosis and Aortic Valve Sclerosis
Anna Reustle1,2, Michael Torzewski3
1Dr. Margarete-Fischer-Bosch-Institute of Clinical Pharmacology, 70376 Stuttgart, Germany. anna.reustle@ikp-stuttgart.de.
Insights
Inflammation drives atherosclerosis and aortic valve sclerosis. The p38 mitogen-activated protein kinase (MAPK) pathway is implicated in these cardiovascular diseases, suggesting it as a potential therapeutic target.
Area of Science:
- Cardiovascular Medicine
- Molecular Biology
- Immunology
Background:
- Atherosclerosis and aortic valve sclerosis are prevalent cardiovascular diseases.
- Current treatments for atherosclerosis (statins) are ineffective for aortic valve sclerosis, leaving surgery as the only option for severe cases.
- Both conditions are inflammatory diseases linked to lipid deposition, not merely degenerative processes.
Purpose of the Study:
- To review experimental findings on p38 mitogen-activated protein kinase (MAPK) in atherosclerosis and aortic valve sclerosis.
- To discuss the potential roles of p38 MAPK in disease progression.
- To evaluate p38 MAPK as a potential pharmacological target.
Main Methods:
- Literature review of experimental studies on p38 MAPK in atherosclerosis and aortic valve sclerosis.
- Analysis of the involvement of p38 MAPK signaling in inflammatory processes within vascular and valvular lesions.
Main Results:
- p38 MAPK is activated by stimuli abundant in atherosclerotic and aortic valve sclerotic lesions, such as oxidative stress and cytokines.
- p38 MAPK signaling elicits diverse responses in different cell types within these lesions.
- These diverse responses may contribute to the progression of atherosclerosis and aortic valve sclerosis.
Conclusions:
- The p38 MAPK pathway is significantly involved in the inflammatory mechanisms underlying atherosclerosis and aortic valve sclerosis.
- Understanding the specific roles of p38 MAPK in different cell types is crucial.
- p38 MAPK represents a promising pharmacological target for treating these cardiovascular diseases.
Abstract:
Atherosclerosis and aortic valve sclerosis are cardiovascular diseases with an increasing prevalence in western societies. Statins are widely applied in atherosclerosis therapy, whereas no pharmacological interventions are available for the treatment of aortic valve sclerosis. Therefore, valve replacement surgery to prevent acute heart failure is the only option for patients with severe aortic stenosis. Both atherosclerosis and aortic valve sclerosis are not simply the consequence of degenerative processes, but rather diseases driven by inflammatory processes in response to lipid-deposition in the blood vessel wall and the aortic valve, respectively. The p38 mitogen-activated protein kinase (MAPK) is involved in inflammatory signaling and activated in response to various intracellular and extracellular stimuli, including oxidative stress, cytokines, and growth factors, all of which are abundantly present in atherosclerotic and aortic valve sclerotic lesions. The responses generated by p38 MAPK signaling in different cell types present in the lesions are diverse and might support the progression of the diseases. This review summarizes experimental findings relating to p38 MAPK in atherosclerosis and aortic valve sclerosis and discusses potential functions of p38 MAPK in the diseases with the aim of clarifying its eligibility as a pharmacological target.
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