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[Changes in heart genome expression in hypertensive diseases]
Insights
Severe hypertension re-expresses cellular fibronectin (c-FN) and beta-myosin heavy chain (beta-MHC) in adult rat hearts. These changes in cardiac gene expression are linked to cardiac hypertrophy and adaptation to hemodynamic overload.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Cardiac Remodeling
Context:
- Chronic increases in hemodynamic load alter cardiac gene expression, leading to cardiac hypertrophy and altered phenotypes.
- Changes in contractile protein gene expression, like isomyosin heavy chains, affect cardiac muscle physiology.
- The precise cellular and molecular mechanisms driving these genomic changes are not fully understood.
Purpose:
- To investigate the cellular and molecular mechanisms underlying cardiac genomic expression changes in response to hemodynamic overload.
- To examine the reexpression of cellular fibronectin (c-FN) and beta-heavy chain of myosin (beta-MHC) in adult rat hearts under severe hypertension.
- To explore the role of beta-adrenergic stimulation in the differential expression of myosin heavy chain (MHC) isoforms in cultured adult rat cardiocytes.
Summary:
- Severe hypertension in adult rats reexpresses mRNAs for cellular fibronectin (c-FN) in coronary arteries and beta-heavy chain of myosin (beta-MHC) in myocytes near these arteries, mirroring fetal gene expression.
- These findings suggest that elevated arterial pressure may trigger factors that modulate the phenotype of both smooth muscle cells and cardiocytes.
- In cultured adult rat cardiocytes, differential MHC isoform expression is linked to beta-adrenergic stimulation, with regulation varying by cell development stage and MHC isoform (alpha vs. beta).
Impact:
- Provides insights into the molecular mechanisms controlling cardiac muscle growth and adaptation to hemodynamic overload, such as in arterial hypertension and heart failure.
- Identifies potential molecular pathways involved in cardiac remodeling, offering targets for therapeutic interventions.
- Enhances understanding of how mechanical stress influences cardiac gene expression and cellular phenotype.
Abstract:
Chronic increases in haemodynamic load modify the expression of cardiac genes, leading to cardiac hypertrophy and a new phenotype. As an example, changes in the expression of the genes encoding the main contractile proteins, the isomyosin heavy chains, have been associated with modifications of the physiological properties of cardiac muscle. The cellular and molecular mechanisms which either do or do not initiate and maintain these changes in cardiac genomic expression remain to be elucidated. Using in situ hybridization we show that mRNAs encoding a cellular form of fibronectin (c-FN), a protein of the basal membrane which is not or poorly expressed in adult rat heart, are reexpressed as a result of severe hypertension with a similar time course than the beta-heavy chain of myosin (beta-MHC), also mostly expressed in fetal heart. The accumulation of the c-FN mRNAs was found in the wall of coronary arteries whilst that of the beta-MHC mRNAs occurred in the myocytes at the border zone of these arteries. Thus a high pressure in the arteries could be the trigger inducing the synthesis of factors which could, through a gradient, modulate the phenotype of both the smooth muscle cells of the media and the cardiocytes. Besides, using a model of cultured adult rat cardiocytes, we show that the differential expression of the MHC isoforms is dependent on the beta-adrenergic stimulation but that the regulation depends on the stage of development of the cells and differs for the alpha and beta MHC. These 2 complementary approaches for identifying the molecular mechanisms that control cardiac muscle growth should help for understanding cardiac adaptation triggered by haemodynamic overload, such as arterial hypertension as well as cardiac failure.