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Published on: March 22, 2017
Transcriptomic analysis of PPARalpha-dependent alterations during cardiac hypertrophy.
Pascal J H Smeets1, Heleen M de Vogel-van den Bosch, Peter H M Willemsen
1Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
Physiological Genomics
|September 25, 2008
Summary
Peroxisome proliferator-activated receptor alpha (PPARalpha) influences cardiac hypertrophy by modulating lipid metabolism and inflammatory pathways. Its absence exacerbates pressure overload effects, highlighting its role beyond lipid regulation.
Area of Science:
- Cardiovascular Biology
- Molecular Metabolism
- Gene Expression Analysis
Background:
- Peroxisome proliferator-activated receptor alpha (PPARalpha) is a key regulator of lipid metabolism and gene expression.
- While PPARalpha is known to mitigate cardiac hypertrophy, its precise mechanisms and signaling pathways remain incompletely understood.
- Understanding PPARalpha's role is crucial for developing targeted therapies for cardiac conditions.
Purpose of the Study:
- To investigate the processes and signaling pathways governed by PPARalpha in the heart under chronic pressure overload.
- To identify novel functions of PPARalpha in cardiac adaptation and maladaptation.
- To utilize whole-genome transcriptomic analysis for a comprehensive understanding.
Main Methods:
- Utilized a mouse model subjected to transverse aortic constriction (TAC) for 28 days.
- Compared gene expression profiles of PPARalpha knockout (PPARalpha-/-) mice with wild-type (WT) littermates using Affymetrix GeneChip Mouse Genome 430 2.0 arrays.
- Analyzed left ventricular gene expression to identify differentially expressed genes and enriched pathways.
Main Results:
- Lack of PPARalpha in unchallenged hearts altered 821 genes, notably those in lipid metabolism and immune response.
- PPARalpha-/- mice exhibited more severe cardiac hypertrophy and greater gene expression changes post-TAC compared to WT mice.
- Hypertrophied PPARalpha-/- hearts showed enrichment in gene clusters associated with extracellular matrix remodeling, immune response, oxidative stress, and inflammation.
Conclusions:
- PPARalpha plays a significant role in regulating cardiac response to pressure overload, extending beyond its known function in lipid metabolism.
- PPARalpha is a critical modulator of immune and inflammatory responses within cardiac muscle.
- These findings reveal PPARalpha as a potential therapeutic target for managing cardiac hypertrophy and associated inflammatory processes.
