A 52-year-old man with long-standing hypertension presents with dyspnea and is found to have left ventricular hypertrophy on echocardiography. Regarding the cellular and molecular basis of cardiac hypertrophy in this condition, all of the following are true EXCEPT:

Question

Accepted Answer

A. Hypertrophic cardiomyocytes show decreased mitochondrial density and reduced oxidative phosphorylation capacity, which is an adaptive response that improves cardiac efficiency. ## Cardiac Hypertrophy: Cellular and Molecular Mechanisms ### Key Point: **Hypertrophic cardiomyocytes develop mitochondrial dysfunction and reduced oxidative capacity — this is MALADAPTIVE, not adaptive.** ### Correct Answer Explanation Option 3 is **FALSE** because: 1. **Mitochondrial dysfunction in cardiac hypertrophy is pathologic**, not beneficial 2. Hypertrophic cardiomyocytes show: - Decreased mitochondrial density relative to myofibril volume - Reduced ATP production capacity - Increased reactive oxygen species (ROS) generation - Impaired calcium handling 3. This mitochondrial dysfunction contributes to **diastolic dysfunction** and eventual **heart failure progression** 4. It is NOT an adaptive response that improves efficiency — it is a maladaptive consequence that worsens cardiac function ### Signaling Pathways in Cardiac Hypertrophy ```mermaid flowchart TD A[Increased Mechanical Stretch
Hypertension, Aortic Stenosis]:::outcome --> B[Integrin-FAK-ILK Activation]:::action A --> C[Angiotensin II-AT1R Signaling]:::action B --> D[MAPK Pathway
ERK1/2, p38, JNK]:::action C --> E[Calcineurin-NFAT Pathway
Calcium-dependent]:::action D --> F[Increased Protein Synthesis
mTOR activation]:::action E --> F F --> G[Fetal Gene Re-expression
ANP, β-MHC, α-SMA]:::outcome F --> H[Cardiomyocyte Enlargement]:::outcome H --> I[Mitochondrial Dysfunction
↓ ATP, ↑ ROS]:::urgent I --> J[Diastolic Dysfunction
Heart Failure]:::urgent ``` ### High-Yield: **Mnemonic for cardiac hypertrophy triggers: STRESS** - **S**tretch (mechanical) - **T**ransgenic (genetic factors) - **R**enin-angiotensin system (Ang II) - **E**ndothelin - **S**ympathetic activation (catecholamines) - **S**ystemic hypertension ### Why the Other Options Are Correct | Statement | Mechanism | Evidence | |---|---|---| | **Integrin-FAK-ILK activation** | Mechanotransduction → MAPK/ERK signaling → protein synthesis | Well-established stretch-sensing pathway | | **AT1R-calcineurin-NFAT** | Ang II → IP3/DAG → Ca²⁺ → calcineurin dephosphorylates NFAT → hypertrophic gene expression | Central to pathologic hypertrophy | | **Fetal gene re-expression** | ANP, β-MHC, α-SMA upregulation in hypertrophy | Marker of pathologic remodeling | ### Clinical Pearl: The transition from **compensatory hypertrophy** (early, maintains function) to **pathologic hypertrophy** (late, causes dysfunction) is marked by: - Loss of mitochondrial integrity - Increased oxidative stress - Activation of apoptotic pathways - Development of diastolic dysfunction - Eventually systolic dysfunction and heart failure

Answer

B. Increased expression of fetal genes such as atrial natriuretic peptide (ANP) and β-myosin heavy chain occurs as part of the hypertrophic response

Answer

C. Activation of angiotensin II type 1 (AT1) receptor signaling leads to increased intracellular calcium and activation of calcineurin-NFAT pathway, promoting hypertrophic gene expression

Answer

D. Increased mechanical stretch of cardiomyocytes activates integrin-linked kinase (ILK) and focal adhesion kinase (FAK), which transduce signals to promote protein synthesis

A 52-year-old man with long-standing hypertension presents with dyspnea and is found to have left ventricular hypertrophy on echocardiography. Regarding the cellular and molecular basis of cardiac hypertrophy in this condition, all of the following are true EXCEPT:

Explanation

Cardiac Hypertrophy: Cellular and Molecular Mechanisms

Key Point:

Correct Answer Explanation

Signaling Pathways in Cardiac Hypertrophy

High-Yield:

Why the Other Options Are Correct

Clinical Pearl:

Practice similar questions

Join our NEET PG community

Statement	Mechanism	Evidence
Integrin-FAK-ILK activation	Mechanotransduction → MAPK/ERK signaling → protein synthesis	Well-established stretch-sensing pathway
AT1R-calcineurin-NFAT	Ang II → IP3/DAG → Ca²⁺ → calcineurin dephosphorylates NFAT → hypertrophic gene expression	Central to pathologic hypertrophy
Fetal gene re-expression	ANP, β-MHC, α-SMA upregulation in hypertrophy	Marker of pathologic remodeling