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Cardiac growth factors
1Department of Medicine, Baylor College of Medicine, Houston, TX 77030.
Insights
Polypeptide growth factors are crucial for heart development and function. Research shows these factors, like transforming growth factor beta 1 and fibroblast growth factors (FGFs), regulate specific genes in cardiac muscle.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Developmental Biology
Background:
- The role of polypeptide growth factors in cardiovascular development, function, and disease is not well understood.
- The myocardium produces various growth factors, including novel ones, which are regulated during cardiac development and disease.
- Growth factor signaling in the heart has unique aspects not observed in simpler biological systems.
Purpose of the Study:
- To investigate the role of polypeptide growth factors in cardiovascular ontogeny and function.
- To explore how specific growth factors, such as transforming growth factor beta 1 and fibroblast growth factors (FGFs), influence cardiac gene expression.
- To understand the distinct mechanisms of growth factor action within the cardiac muscle lineage.
Main Methods:
- Analysis of growth factor production and regulation in the myocardium during development and disease.
- Investigating the effects of transforming growth factor beta 1 and fibroblast growth factors (FGFs) on cardiac-specific gene expression.
- Examining the selective induction of gene elements, like the serum response element for alpha-actin, by different FGF isoforms in cardiac myocytes.
Main Results:
- Transforming growth factor beta 1 and fibroblast growth factors (FGFs) were found to selectively up-regulate genes specific to the fetal myocardium.
- Basic FGF activated the gene encoding the skeletal muscle isoform of alpha-actin, while acidic FGF inhibited it.
- Basic FGF, but not acidic FGF, selectively induced a serum response element in cardiac myocytes.
Conclusions:
- Cardiac muscle serves as a valuable model for studying growth factor signaling pathways that control differentiated gene transcription.
- Specific growth factors play distinct roles in directing cardiac organogenesis and adaptation.
- Understanding these signaling pathways is critical for comprehending cardiovascular development and disease.
Abstract:
The role of polypeptide growth factors in cardiovascular ontogeny, function, and pathologic states is poorly understood. Recent investigations demonstrate that the myocardium produces both known and novel growth factors, which are highly regulated during development and disease, and have suggested that peptide growth factors may direct cardiac organogenesis and adaptation. Aspects of growth factor production, transduction, and action in myocardium are distinct to the cardiac muscle lineage and were not foreseen from results in simpler systems. Transforming growth factor beta 1 and fibroblast growth factors (FGFs) selectively up-regulate an ensemble of tissue-specific genes associated with the fetal myocardium. One of these, encoding the skeletal muscle isoform of alpha-actin, is activated by basic FGF yet is inhibited by acidic FGF. A serum response element of this gene is selectively induced, in cardiac myocytes, by basic FGF but not acidic FGF. Thus, cardiac muscle is an especially intriguing model for the analysis of growth factor signalling pathways that control differentiated gene transcription.