cardiac muscle hypertrophy in response to stress

Definition

Target type: biologicalprocess

The physiological enlargement or overgrowth of all or part of the heart muscle due to an increase in size (not length) of individual cardiac muscle fibers, without cell division, as a result of a disturbance in organismal or cellular homeostasis. [GOC:BHF, GOC:mtg_cardiac_conduct_nov11, GOC:mtg_muscle]

Cardiac muscle hypertrophy is a complex process that involves an increase in the size of individual cardiomyocytes (heart muscle cells) in response to various stressors. This adaptive response is essential for maintaining heart function under conditions of increased workload or injury. However, excessive hypertrophy can lead to heart failure.

The process of cardiac hypertrophy is driven by a multitude of signaling pathways, including the calcineurin-NFAT, MAPK, and PI3K/Akt pathways. These pathways are activated by mechanical stress, such as increased blood pressure or volume, and by neurohormonal factors like angiotensin II and endothelin-1.

**Here's a detailed breakdown of the major steps involved in cardiac hypertrophy:**

**1. Stress Recognition and Signal Transduction:**
- Mechanical stress (increased blood pressure or volume) triggers the activation of stretch-activated ion channels and integrins on the cardiomyocyte membrane.
- Neurohormonal factors, such as angiotensin II and endothelin-1, bind to their specific receptors on the cardiomyocyte membrane, initiating intracellular signaling cascades.

**2. Activation of Transcription Factors:**
- The activated signaling pathways converge on various transcription factors, including NFAT, GATA4, MEF2, and others. These transcription factors regulate the expression of genes involved in cardiac hypertrophy.

**3. Gene Expression and Protein Synthesis:**
- Transcription factors activate the transcription of target genes, leading to the synthesis of proteins that contribute to hypertrophy. These proteins include:
- **Structural proteins:** Actin, myosin, titin, and other proteins that increase the size and strength of the cardiomyocyte.
- **Sarcomere proteins:** Proteins that enhance the contractile apparatus of the cardiomyocyte.
- **Growth factors:** Factors like IGF-1 and TGF-beta, which promote cell growth and survival.
- **Cytokines:** Inflammatory mediators like TNF-alpha and IL-6, which can contribute to the hypertrophic process.

**4. Cardiomyocyte Growth and Remodeling:**
- The synthesis of new proteins leads to an increase in the size and volume of the cardiomyocyte.
- The sarcomere, the basic contractile unit of the heart, is reorganized and expanded, enhancing contractility.
- The cardiomyocyte also undergoes changes in its metabolism and energy production to meet the increased demands of the hypertrophied heart.

**5. Compensatory Hypertrophy and Pathological Hypertrophy:**
- **Compensatory hypertrophy** is a beneficial adaptive response to stress. It allows the heart to maintain its function in the face of increased workload or injury.
- **Pathological hypertrophy** occurs when hypertrophy is excessive and leads to adverse changes in heart function. This can occur due to prolonged or severe stress, genetic predispositions, or other factors. Pathological hypertrophy can result in:
- **Heart failure:** The heart muscle is unable to pump blood effectively.
- **Arrhythmias:** Irregular heartbeat.
- **Increased risk of sudden cardiac death:** Due to electrical instability in the heart.

**In summary, cardiac muscle hypertrophy is a complex process with both adaptive and pathological aspects. It involves the activation of signaling pathways, the regulation of gene expression, and the synthesis of proteins that contribute to cardiomyocyte growth and remodeling. While compensatory hypertrophy can be beneficial, pathological hypertrophy can have serious consequences for heart health.**
'"

Proteins (6)

Compounds (116)