positive regulation of cardiac muscle hypertrophy

Definition

Target type: biologicalprocess

Any process that increases the rate, frequency or extent of the enlargement or overgrowth of all or part of the heart due to an increase in size (not length) of individual cardiac muscle fibers, without cell division. [GOC:BHF, GOC:dph, GOC:tb]

Positive regulation of cardiac muscle hypertrophy is a complex biological process involving a coordinated interplay of signaling pathways, transcription factors, and gene expression. This process is essential for the heart's ability to adapt to increased workload, such as during exercise or in response to pathological conditions like hypertension.

**Key Molecular Players and Mechanisms:**

* **Hypertrophic Stimuli:** Cardiac muscle hypertrophy can be triggered by a variety of stimuli, including mechanical stretch (increased workload), neurohormonal factors (e.g., angiotensin II, catecholamines), and growth factors (e.g., insulin-like growth factor 1, fibroblast growth factor).
* **Signal Transduction Pathways:** These stimuli activate signaling pathways that converge on a series of downstream targets, ultimately leading to gene expression changes. Some critical pathways include:
* **MAPK Pathway:** Mitogen-activated protein kinase (MAPK) pathways, such as the ERK1/2, JNK, and p38 pathways, are crucial for initiating hypertrophic signaling.
* **PI3K/Akt Pathway:** Phosphatidylinositol 3-kinase (PI3K)/Akt pathway is involved in cell survival, growth, and protein synthesis.
* **Calcineurin/NFAT Pathway:** Calcineurin, a calcium-dependent phosphatase, activates nuclear factor of activated T-cells (NFAT), a transcription factor that promotes hypertrophy.
* **Ca2+/Calmodulin Kinase Pathway:** Increased intracellular calcium levels activate calcium/calmodulin-dependent kinases (CaMKs) that contribute to hypertrophy signaling.
* **Transcription Factors:** These proteins bind to specific DNA sequences and regulate gene expression. Key transcription factors involved in cardiac hypertrophy include:
* **GATA4, MEF2:** These transcription factors are involved in the expression of genes essential for cardiac muscle development and function.
* **NFAT:** As mentioned earlier, NFAT plays a critical role in promoting hypertrophy.
* **SRF:** Serum response factor (SRF) is a transcription factor that is activated by mechanical stretch and promotes expression of genes involved in hypertrophy.
* **Gene Expression Changes:** Ultimately, the signaling pathways converge on the regulation of gene expression, leading to changes in protein synthesis and the overall growth of cardiac muscle cells.

**Key Genes Regulated During Hypertrophy:**

* **Cardiac Myosin Heavy Chain (MHC):** MHC isoforms are switched from the slow, beta-MHC to the fast, alpha-MHC, reflecting the increased contractility needed for hypertrophy.
* **Sarcomeric Proteins:** Other sarcomeric proteins involved in muscle contraction, such as actin, troponin, and tropomyosin, are upregulated.
* **Cardiac Hypertrophy-Specific Genes:** Several genes, including ANP, BNP, and skeletal alpha-actin, are specifically induced during hypertrophy and contribute to the pathological remodeling of the heart.

**Regulation and Consequences:**

* **Positive and Negative Regulators:** The process of cardiac hypertrophy is tightly regulated by both positive and negative regulators. Negative regulators, such as the transcription factor KLF15, can dampen the hypertrophic response and protect against excessive growth.
* **Beneficial and Pathological Hypertrophy:** While hypertrophy can be an adaptive response to increased workload, excessive or prolonged hypertrophy can lead to pathological changes, including heart failure.

The complex nature of positive regulation of cardiac muscle hypertrophy makes it an important area of research with the potential to develop therapies for heart failure and other cardiovascular diseases.'
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Proteins (14)

Compounds (599)