CARDIAC HYPERTROPHY AT THE CELLULAR LEVEL: LITERATURE REVIEW

Cardiac hypertrophy (CH) is an adaptive increase in myocardial mass that initially serves to normalize wall stress and preserve cardiac output in response to chronic hemodynamic overload. However, persistent stimulation transforms this compensatory process into pathological remodeling, characterized by cardiomyocyte dysfunction, fibrosis, and eventual heart failure. This comprehensive review explores CH at the cellular and molecular levels, emphasizing distinctions between physiological and pathological hypertrophy, as well as the microstructural, metabolic, and signaling alterations underlying disease progression.Physiological hypertrophy—observed in athletes and pregnancy—is reversible, maintains capillary density, and preserves function. In contrast, pathological hypertrophy (pressure- or volume-induced) involves unbalanced sarcomere addition, altered calcium handling, extracellular matrix expansion, and irreversible fibrosis. Recent advances in imaging, such as diffusion tensor MRI (DTI), enable in vivo visualization of myofiber disarray and extracellular remodeling, improving differentiation from conditions like hypertrophic cardiomyopathy (HCM). At the molecular level, maladaptive CH is driven by activation of Calcineurin/NFAT and MAPK pathways, neurohumoral signaling (AngII/GPCR), redox imbalance, and epigenetic dysregulation involving HDACs and non-coding RNAs. Mitochondrial dysfunction and metabolic reprogramming toward glycolysis precede contractile failure, linking energetic impairment to structural decline. Genetic insights reveal that sarcomeric mutations, particularly in MYBPC3 and β-myosin heavy chain, alter contractility and energy utilization, fueling debates over mechanisms like haploinsufficiency and hypercontractility.Ultimately, CH represents a convergence of biomechanical stress, molecular signaling, and metabolic disturbance. Future directions should focus on integrative omics, genotype-specific therapies, and earlier imaging-based detection of irreversible fibrosis. These approaches may enable precision interventions that halt or reverse pathological remodeling before the onset of heart failure.