Understand the source comparison
Myostatin and Cardiomyocyte Hypertrophy: Physiological vs Pathological Contexts
The distinction between physiological and pathological cardiac hypertrophy is mechanistically critical for interpreting ACE-031’s cardiac biology. Physiological hypertrophy (exercise-induced, pregnancy-associated) is driven by PI3K-Akt-mTORC1 — cardiomyocytes
No winner is assigned.
This page preserves a source comparison for education. It does not add a rating, recommendation or clinical judgment.
- The distinction between physiological and pathological cardiac hypertrophy is mechanistically critical for interpreting ACE-031’s cardiac biology. Physiological hypertrophy (exercise-induced, pregnancy-associated) is driven by PI3K-Akt-mTORC1 — cardiomyocytes enlarge proportionally with preserved wall geometry (eccentric: chamber volume increases proportionally with wall thickness, maintaining normal wall stress), normal or improved systolic function, no fibrosis, and normalisation upon stimulus removal. Pathological hypertrophy (pressure overload, neurohumoral activation) is driven by calcineurin-NFAT, NF-κB, and β-adrenergic/Gαq pathways — concentric (wall thickness disproportionate to chamber volume), associated with interstitial fibrosis, β-MHC isoform switch, and progressive systolic failure.
- Myostatin restrains both forms: in physiological hypertrophy (voluntary wheel running, swim training), Mstn⁻/⁻ mice develop exaggerated cardiac hypertrophy (higher HW:BW, larger cardiomyocyte CSA) that is functional — demonstrating that myostatin normally limits physiological hypertrophic reserve. In pathological overload (TAC), Mstn⁻/⁻ mice show a more complex phenotype: initial preservation of cardiac function but accelerated decompensation at later timepoints in some studies, possibly because the enhanced hypertrophic growth without proportional fibrosis attenuation eventually exceeds coronary perfusion capacity. ACE-031 in TAC must be evaluated across multiple timepoints (4, 6, 8, 12 weeks) with both echocardiographic and pressure-volume loop endpoints to capture this temporal dynamic.