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Hypertrophy
Hypertrophy
Hypertrophy
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Hypertrophy
Hypertrophy results from an increase in cell size, whereas hyperplasia stems from an increase in cell number.

Hypertrophy is the increase in the volume of an organ or tissue due to the enlargement of its component cells.[1] It is distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number.[2] Although hypertrophy and hyperplasia are two distinct processes, they frequently occur together, such as in the case of the hormonally induced proliferation and enlargement of the cells of the uterus during pregnancy.

Eccentric hypertrophy is a type of hypertrophy where the walls and chamber of a hollow organ undergo growth in which the overall size and volume are enlarged. It is applied especially to the left ventricle of heart.[3] Sarcomeres are added in series, as for example in dilated cardiomyopathy (in contrast to hypertrophic cardiomyopathy, a type of concentric hypertrophy, where sarcomeres are added in parallel).

[edit]
-plasia and -trophy
  • Abiotrophy (loss in vitality of organ or tissue)
  • Atrophy (reduced functionality of an organ, with decrease in the number or volume of cells)
  • Hypertrophy (increase in the volume of cells or tissues)
  • Hypotrophy (decrease in the volume of cells or tissues)
  • Dystrophy (any degenerative disorder resulting from improper or faulty nutrition)

See also

[edit]

References

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Hypertrophy

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from Grokipedia
Hypertrophy refers to the enlargement of an organ or tissue resulting from an increase in the size of its individual cells, rather than an increase in cell number, which is known as . This adaptive response can be physiological, occurring in response to normal demands such as exercise, , or developmental growth, leading to enhanced function without harm. For instance, hypertrophy develops through resistance training, increasing muscle fiber cross-sectional area to improve strength and performance. Similarly, during , the undergoes physiological hypertrophy to accommodate fetal growth, reverting postpartum without . In athletes, cardiac hypertrophy from endurance or enhances heart capacity while maintaining normal function. In contrast, pathological hypertrophy arises from or disease, often impairing organ function and progressing to failure if untreated. Common examples include in the heart, where high causes thickening of the ventricular wall, reducing pumping efficiency and raising risks of arrhythmias or . Other instances occur in conditions like , a leading to abnormal myocardial thickening that obstructs blood flow. Pathological forms are typically maladaptive, involving and altered gene expression, distinguishing them from beneficial physiological changes. Key mechanisms driving hypertrophy include mechanical overload, hormonal signals (e.g., insulin-like growth factor-1), and cellular pathways like the PI3K/Akt/ route, which promote protein synthesis and inhibit degradation. Understanding these processes is crucial for therapeutic interventions, such as exercise regimens to induce beneficial hypertrophy or medications to regress harmful forms.

Definition and Overview

Definition

Hypertrophy refers to the increase in the size of an organ or tissue through the enlargement of its individual cells, without a corresponding increase in cell number, distinguishing it from other growth processes like . This adaptive or maladaptive response allows tissues to meet heightened functional demands or compensate for stress, occurring in various biological contexts such as organ regeneration or chronic loading. The term "hypertrophy" derives from the Greek words hyper (meaning "excess" or "over") and trophē (meaning "nourishment"), reflecting the concept of excessive cellular growth or nourishment. It was defined in modern medical pathology by in his seminal 1858 work Cellular Pathology, where he differentiated it from related cellular changes. At its core, hypertrophy involves a net positive balance where protein synthesis outpaces protein degradation within cells, leading to expanded cellular volume and overall tissue mass. A classic example is liver hypertrophy following partial , where the remaining hepatocytes enlarge to restore organ function before full regeneration occurs. Quantitatively, hypertrophy is often assessed by relative organ weight, calculated as the ratio of organ mass to body weight, providing a standardized measure of enlargement independent of overall body size. Hypertrophy can manifest as physiological, serving adaptive purposes like enhanced workload capacity, or pathological, arising from disease states such as , though both share the fundamental cellular mechanism of size increase. Hypertrophy is fundamentally distinct from , the latter being an adaptive process involving an increase in tissue mass through proliferation and an elevated number of cells, whereas hypertrophy achieves growth via enlargement of existing cells without altering their count. Although both can coexist and contribute to organ enlargement in response to stimuli like hormonal influences or mechanical stress, their mechanisms diverge: relies on mitotic , while hypertrophy emphasizes intracellular accumulation of proteins, organelles, and myofibrils. Atrophy presents the converse of , manifesting as a decrease in cell and organ size due to accelerated protein degradation that outpaces synthesis, commonly triggered by disuse, ischemia, or . In atrophying cells, ubiquitin-proteasome pathways and dominate, leading to dismantling of structural components like myofibrils and mitochondria, in stark contrast to the anabolic, synthetic dominance in hypertrophic cells. Unlike these quantitative changes in cell size or number, metaplasia entails a qualitative shift where one differentiated is replaced by another within the same tissue, serving as an adaptive response to persistent or altered environmental cues. This transformation, often reversible, does not involve alterations in cell dimensions but rather a of cellular to better withstand stress. Hypertrophy frequently functions in an as a compensatory mechanism to accommodate heightened or functional demands, enabling tissues to sustain performance without relying on .

Types of Hypertrophy

Physiological Hypertrophy

Physiological hypertrophy represents an adaptive, non-pathological enlargement of cells or tissues in response to increased functional demands, characterized by reversible growth that enhances organ efficiency without compromising health. This process involves the expansion of individual cell size, primarily through increased protein synthesis and proliferation, allowing tissues to better meet physiological needs such as heightened workload or volume requirements. Unlike hyperplastic growth, which adds new cells, physiological hypertrophy maintains cell number while optimizing performance in healthy individuals. A prominent example occurs in , where resistance training stimulates hypertrophy, resulting in greater cross-sectional area and contractile capacity to support enhanced . In this context, mechanical overload from exercises like triggers muscle fiber enlargement, enabling athletes to generate more force and sustain prolonged efforts. Similarly, during , the experiences physiological hypertrophy driven by and mechanical stretch, expanding from approximately 70 grams to over 1,100 grams to accommodate fetal development and maintain maternal-fetal circulation. The benefits of physiological hypertrophy are evident in improved organ function tailored to specific demands; for instance, in endurance or strength athletes, growth augments power output and fatigue resistance, while cardiac hypertrophy—known as athlete's heart—increases and overall to support elevated aerobic capacity. These adaptations promote superior performance and metabolic efficiency without long-term detriment. This form of hypertrophy is typically reversible upon removal of the inducing stimulus, ensuring tissue . In , detraining leads to gradual , with muscle mass declining as training ceases, often within weeks to months depending on prior level. Likewise, postpartum uterine involution facilitates rapid regression of hypertrophy, restoring the to near pre-pregnancy dimensions through and tissue remodeling within 4-6 weeks. Cardiac adaptations in athletes also regress with prolonged detraining, as evidenced by reductions in left ventricular mass after 1 month of complete detraining.

Pathological Hypertrophy

Pathological hypertrophy is characterized by the maladaptive enlargement of cells or tissues in response to chronic disease-related stressors, potentially leading to irreversible structural changes and progressive if untreated, distinguishing it from the reversible, beneficial adaptations seen in physiological hypertrophy. This process involves excessive protein synthesis and reorganization, often triggered by sustained hemodynamic overload or hormonal imbalances, leading to a shift toward fetal patterns that impair normal cellular function. However, early treatment of the underlying cause can promote regression of pathological hypertrophy in some cases. Common causes include chronic pressure overload from conditions such as or aortic valvular stenosis, volume overload from , and endocrine disorders like , where excess and insulin-like growth factor-1 drive widespread tissue enlargement. In the renal system, unilateral can induce compensatory hypertrophy in the contralateral as an initial adaptive response that becomes pathological over time due to persistent ischemia. The consequences of pathological hypertrophy include increased tissue stiffness, reduced compliance, and heightened susceptibility to fibrosis and programmed cell death via apoptosis, which collectively contribute to organ failure, such as heart failure in cardiac cases or progressive renal insufficiency. For instance, in the heart, this manifests as concentric hypertrophy from pressure overload, promoting interstitial fibrosis and arrhythmogenic risk, whereas eccentric patterns from volume overload exacerbate chamber dilation and systolic dysfunction. In acromegaly, pathological cardiac hypertrophy often leads to diastolic impairment and increased cardiovascular mortality if untreated.

Mechanisms of Hypertrophy

Cellular and Molecular Basis

Hypertrophy at the cellular level fundamentally involves an increase in cell size through enhanced protein synthesis and reduced degradation, leading to net accumulation of cellular components. This process is driven by the upregulation of ribosomal biogenesis, which expands the protein synthetic machinery to support higher rates of . For instance, the proliferation of ribosomes allows cells to produce more myofibrillar proteins, such as and , which are essential structural elements in muscle cells. Additionally, hypertrophy is characterized by the proliferation of s, including mitochondria, to meet the increased energy demands of enlarged cells. This organelle expansion ensures that cellular can sustain the growth without compromising function. Molecular triggers for hypertrophy include mechanical stimuli like stretch and biochemical signals from hormones and growth factors. Mechanical stretch on cell membranes activates mechanosensitive ion channels, leading to calcium influx that influences downstream cellular responses. Hormones such as (IGF-1) and growth factors bind to cell surface receptors, initiating cascades that activate transcription factors like nuclear factor of activated T-cells (NFAT). NFAT translocation to the nucleus promotes the expression of genes involved in hypertrophy, such as those encoding hypertrophy-associated proteins. These triggers ensure that hypertrophy is a coordinated response to environmental cues, maintaining cellular . The balance of is central to hypertrophy, where net protein accretion is determined by the equation: net protein accretion = protein synthesis rate - protein degradation rate. During hypertrophy, this balance shifts favorably through accelerated synthesis and suppressed degradation. A key mechanism for reducing degradation involves inhibition of the ubiquitin-proteasome system (UPS), the primary pathway for protein breakdown in cells. UPS inhibition prevents the tagging and degradation of contractile proteins, allowing their accumulation and contributing to cell enlargement. This regulated is crucial for the sustained growth observed in hypertrophic responses. Hypertrophy also entails shifts in cellular energy metabolism to support biosynthetic demands. In many cases of hypertrophy, cells exhibit increased glycolytic activity (aerobic glycolysis), providing biosynthetic precursors and rapid ATP to support growth, while oxidative metabolism may also adapt to meet energy demands. This metabolic reprogramming is modulated by AMP-activated protein kinase (AMPK), which senses energy status and adjusts metabolic flux accordingly. When activated, AMPK promotes catabolic processes but can be inhibited during hypertrophy to favor anabolic pathways, ensuring sufficient energy for protein synthesis and organelle biogenesis.

Key Signaling Pathways

The mammalian target of rapamycin (mTOR) pathway functions as a central regulator of protein synthesis during hypertrophic responses across various tissues, including skeletal and cardiac muscle. Activated by anabolic stimuli such as amino acids (e.g., leucine) and mechanical loading, mTOR complex 1 (mTORC1) phosphorylates downstream targets like S6 kinase 1 (S6K1) and 4E-binding protein 1 (4E-BP1), thereby enhancing ribosomal biogenesis and translation initiation to support cellular enlargement. In growth factor signaling, insulin-like growth factor 1 (IGF-1) initiates the pathway through phosphoinositide 3-kinase (PI3K), which recruits and activates Akt (also known as protein kinase B). Akt then phosphorylates tuberous sclerosis complex 2 (TSC2) at multiple sites (e.g., Ser939, Thr1462), inhibiting its GTPase-activating protein (GAP) function toward Ras homolog enriched in brain (Rheb); this allows Rheb-GTP accumulation and subsequent mTORC1 activation on lysosomes. Genetic or pharmacological blockade of mTOR, such as with rapamycin, prevents hypertrophy induced by overload or IGF-1 in rodent models, underscoring its essential role. The calcineurin-nuclear factor of activated T-cells (NFAT) pathway represents a key calcium-sensitive cascade in hypertrophy, particularly in response to mechanical stress or neurohormonal signals. Upon elevation of intracellular calcium levels, binds and activates the , which dephosphorylates NFAT transcription factors (e.g., NFATc1, NFATc3), promoting their nuclear translocation and cooperation with other factors like GATA-2 to induce expression of hypertrophic , including the fetal gene program (e.g., atrial natriuretic factor, β-myosin heavy chain). This pathway is implicated in both physiological and pathological hypertrophy; for instance, transgenic overexpression of activated in cardiomyocytes triggers rapid hypertrophic growth reversible by cyclosporine A, a calcineurin inhibitor. In , -NFAT signaling similarly drives fiber-type switching and hypertrophy in response to chronic loading. The /extracellular signal-regulated kinase (MAPK/ERK) pathway contributes to hypertrophic gene transcription, especially under stress conditions like pressure overload or II stimulation. This cascade begins with ligand binding to receptor tyrosine kinases or G-protein-coupled receptors, activating Ras, which recruits to phosphorylate and activate (MEK1/2); MEK then dual-phosphorylates ERK1/2 (Thr202/Tyr204), enabling ERK nuclear entry and phosphorylation of targets such as Elk-1 and GATA4 to upregulate immediate-early genes (e.g., c-fos, c-jun) and sarcomeric proteins. Sustained ERK activation correlates with adaptive hypertrophy in transgenic models overexpressing MEK1, enhancing contractility without , though chronic activation can shift toward maladaptive remodeling. These pathways integrate through cross-talk to fine-tune hypertrophic responses; notably, IGF-1 stimulates both via PI3K/Akt and -NFAT signaling, as evidenced by IGF-1-induced myocyte hypertrophy requiring activity for NFAT/GATA-2-mediated transcription alongside -dependent protein synthesis. ERK can intersect with by phosphorylating TSC2, further amplifying anabolic outputs under combined growth and stress cues. This convergence allows coordinated regulation, where pathway balance determines whether hypertrophy remains physiological or progresses to .

Applications in Specific Tissues

Skeletal Muscle Hypertrophy

hypertrophy is the enlargement of fibers, primarily driven by resistance exercise, resulting in increased muscle cross-sectional area (CSA) and force production capacity. This process exemplifies physiological hypertrophy, where adaptations enhance performance without pathological consequences. It occurs mainly in type II (fast-twitch) fibers but can affect type I fibers to a lesser extent, supporting greater overall muscle mass and strength. The primary mechanism of skeletal muscle hypertrophy involves the addition of contractile myofibrils within existing muscle fibers. Myofibrils increase in number (parallel addition) to expand fiber diameter, thereby boosting CSA and strength, or in series to accommodate length changes during growth. This protein accretion outpaces degradation, driven by mechanical tension from loading, which activates mechanosensors like integrins and focal adhesion kinase to initiate signaling for protein synthesis. Satellite cell fusion contributes new myonuclei to support this expansion, particularly in sustained or high-volume training, but plays a minimal direct role in initial size gains, as hypertrophy can proceed via domain expansion of existing nuclei. Key stimuli for hypertrophy include resistance training employing , where loads are incrementally increased to challenge muscle fibers beyond their current capacity. For instance, abdominal muscles do not develop significant hypertrophy from everyday activities, as these provide insufficient resistance to elicit the necessary mechanical overload; targeted resistance exercises are required to stimulate growth. This elicits mechanical tension, metabolic stress, and minor muscle damage, all promoting hypertrophic signaling. Hormonal factors, notably testosterone, amplify these responses by binding androgen receptors in muscle cells, enhancing protein synthesis and satellite cell activity without requiring new myonuclear addition in early phases. Two distinct types of hypertrophy are recognized: myofibrillar and sarcoplasmic. Myofibrillar hypertrophy emphasizes growth in contractile proteins ( and ), leading to denser myofibrils and greater strength gains, typically from heavy-load training (e.g., 70-85% of ). In contrast, sarcoplasmic hypertrophy involves expansion of the —the fluid-filled compartment containing , mitochondria, and non-contractile proteins—potentially enhancing endurance and metabolic capacity, often observed in higher-repetition schemes. While both contribute to overall size, evidence suggests myofibrillar changes predominate in most training contexts, with sarcoplasmic adaptations being less pronounced and context-specific. Measurement of skeletal muscle hypertrophy focuses on changes in fiber or whole-muscle CSA, assessed non-invasively via (MRI) or for accuracy and reliability, or invasively through muscle biopsy to quantify individual fiber dimensions. In novice trainees, resistance can yield notable early gains, with quadriceps CSA increasing by approximately 5-10% over the first few months, reflecting rapid neural and structural adaptations before plateauing. These metrics establish the scale of adaptation, with longitudinal studies confirming progressive improvements tied to volume and intensity.

Cardiac Muscle Hypertrophy

Cardiac muscle hypertrophy, or left ventricular hypertrophy (LVH), represents an adaptive response of the heart to increased hemodynamic stress, primarily involving enlargement of cardiomyocytes to maintain cardiac output. This process is classified into two main types based on the underlying stimulus and resulting geometry: concentric and eccentric hypertrophy. Concentric hypertrophy occurs in response to pressure overload, such as in chronic hypertension or aortic stenosis, leading to thickening of the ventricular walls without significant chamber dilation; this remodeling normalizes systolic wall stress by increasing wall thickness relative to chamber radius. In contrast, eccentric hypertrophy develops under volume overload conditions, like mitral or aortic regurgitation, resulting in chamber dilation and proportional wall thickening to accommodate increased preload and reduce diastolic wall stress. These adaptations initially preserve cardiac function but can predispose the heart to maladaptive changes over time. At the pathophysiological level, cardiac hypertrophy involves the re-expression of a fetal gene program, characterized by upregulation of genes such as (ANP) and (BNP), which are markers of the hypertrophic response and help regulate and vascular tone. This molecular shift, triggered by mechanical stress and neurohormonal activation, supports initial compensatory growth but can progress to . A key mechanism in this transition to heart failure is increased cardiomyocyte , where and downregulation of survival signaling pathways lead to myocyte loss, , and ventricular dilation, ultimately impairing contractility. Studies in pressure-overload models demonstrate that apoptotic rates rise during the shift from compensated hypertrophy to failure, contributing to reduced myocyte number and systolic dysfunction. Risk factors for cardiac hypertrophy include aging, which promotes structural remodeling through cumulative hemodynamic and inflammatory changes, and , which exacerbates load via , , and direct lipotoxic effects on cardiomyocytes. Epidemiological data indicate a prevalence of LVH in 20-40% of hypertensive patients, with higher rates in those with uncontrolled or comorbidities like , underscoring the role of modifiable factors in disease progression. Long-term outcomes of untreated hypertrophy often involve initial compensation for workload through enhanced contractility, but progression to diastolic dysfunction is common, where impaired relaxation and increased stiffness limit ventricular filling, elevating risks for with preserved . This diastolic impairment correlates with adverse events like arrhythmias and sudden death.

Hypertrophy in Other Organs

Hypertrophy in the liver serves as an initial regenerative mechanism following partial or resection, where the remaining hepatic tissue undergoes transient compensatory enlargement to support subsequent restoration of organ mass and function. This process begins with hypertrophy (enlargement) of , followed primarily by (proliferation), driven by the rapid upregulation of hepatocyte growth factor (HGF), a potent produced by nonparenchymal cells such as hepatic stellate cells and endothelial cells shortly after injury. HGF binds to its receptor c-Met on hepatocytes, initiating signaling cascades that promote and , thereby facilitating the adaptive response to maintain liver . In the , hypertrophy occurs as a compensatory adaptation after unilateral , leading to enlargement of the remnant kidney's glomeruli and tubules to handle increased load. This involves and hypertrophy of tubular epithelial cells, initially preserving renal function, but can progress to pathological states like glomerular sclerosis and tubulointerstitial if sustained. In , further exacerbates renal hypertrophy through mechanisms including mesangial expansion and thickening of the , ultimately contributing to sclerosis and declining kidney function. Prostate hypertrophy is a prominent feature of (BPH), a common age-related condition characterized by the non-malignant enlargement of glandular and stromal tissues, often driven by s. signaling, particularly via , promotes the proliferation and hypertrophy of prostate epithelial and stromal cells, with evidence showing that individuals with androgen deficiencies, such as those castrated prepubertally, do not develop BPH. This androgen-dependent process underlies the progressive growth that can obstruct urinary flow, though estrogens may also play a permissive role in modulating the response. Endocrine organs also exhibit hypertrophy in response to specific stressors. In the , iodine triggers compensatory hypertrophy and of follicular cells, stimulated by elevated (TSH) levels that attempt to enhance uptake and thyroid hormone synthesis, resulting in endemic goiter. Similarly, the adrenal glands can undergo hypertrophy under acute or chronic stress, involving enlargement of the and reticularis due to (ACTH) overstimulation, which boosts production; this response is often reversible upon stress resolution and may include both hyperplastic and hypertrophic components in a region-specific manner.

Clinical and Research Aspects

Diagnosis and Measurement

Diagnosis and measurement of hypertrophy involve a combination of non-invasive imaging, biomarker analysis, functional tests, and invasive procedures to detect and quantify tissue enlargement in clinical and research contexts. In cardiac hypertrophy, echocardiography serves as a primary imaging modality, enabling the calculation of left ventricular mass index (LVMI) through 2D or M-mode measurements of wall thickness and chamber dimensions, with LVMI values exceeding 115 g/m² in men and 95 g/m² in women indicating left ventricular hypertrophy (LVH). This technique provides real-time assessment of hypertrophy patterns and is recommended by guidelines for initial evaluation due to its accessibility and ability to differentiate physiological from pathological changes. For skeletal muscle hypertrophy, magnetic resonance imaging (MRI) is considered the gold standard for quantifying muscle volume and cross-sectional area (CSA), offering precise volumetric analysis without radiation exposure and high reproducibility for tracking changes over time. Biomarkers play a supportive role in detecting and monitoring hypertrophy, particularly in cardiac cases. Elevated levels of B-type natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP) in serum indicate myocardial stress and correlate with hypertrophy severity and clinical outcomes in conditions like (HCM). Similarly, high-sensitivity or T elevations reflect myocyte injury associated with pathological cardiac hypertrophy, aiding in risk stratification alongside imaging. For cellular-level verification across tissues, muscle remains essential, involving histological analysis to measure fiber diameter or CSA, where increases in mean fiber size confirm hypertrophic remodeling; semi-automated tools enhance accuracy in quantifying these parameters from cross-sections. Functional assessments complement structural evaluations, with (ECG) providing indirect evidence of cardiac hypertrophy through voltage criteria. Common ECG indices for LVH include the Sokolow-Lyon criterion (S wave in V1 plus R wave in V5 or V6 >35 mm) and Cornell voltage criteria (S in V3 plus R in aVL >28 mm in men or >20 mm in women), which detect increased electrical forces from thickened myocardium, though sensitivity varies (around 20-50%) compared to . In settings, animal models facilitate controlled studies of hypertrophy induction and progression. The transverse aortic constriction (TAC) model in mice or rats creates pressure overload to mimic cardiac hypertrophy, allowing longitudinal assessment of via or , and is widely used to evaluate molecular mechanisms and therapeutic targets. These methods collectively enable precise diagnosis and quantification, tailored to specific tissues such as cardiac or .

Therapeutic Implications

Pharmacological interventions play a central role in managing pathological hypertrophy, particularly in the cardiac context. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have demonstrated efficacy in regressing left ventricular hypertrophy (LVH) by interrupting the renin-angiotensin-aldosterone system, which contributes to myocyte growth and fibrosis. Clinical evidence from meta-analyses shows that ACE inhibitors like ramipril not only regress ECG-detected LVH but also prevent its progression in hypertensive patients with controlled blood pressure. Similarly, ARBs such as losartan reduce left ventricular mass beyond blood pressure lowering alone, with studies indicating superior reversal of LVH compared to other antihypertensives. Beta-blockers, including propranolol and metoprolol, mitigate hypertrophy by reducing cardiac load and heart rate, thereby alleviating pressure overload and improving diastolic filling in conditions like hypertrophic cardiomyopathy. These agents also suppress endoplasmic reticulum stress and attenuate hypertrophic signaling, leading to decreased fibrosis and enhanced cardiac function. Lifestyle modifications offer non-pharmacological strategies to influence hypertrophy, emphasizing the promotion of physiological adaptations over pathological ones. Structured exercise protocols, such as aerobic , induce physiological cardiac hypertrophy characterized by improved contractility and density without , contrasting with the maladaptive remodeling in overload states. Resistance and exercises can shift hypertrophic responses toward beneficial pathways by PI3K/Akt signaling while inhibiting pathological calcineurin-NFAT , as evidenced in animal models and athletes. Emerging therapies aim to target molecular drivers of hypertrophy with greater specificity. Gene therapy approaches inhibiting mTORC1 via PRAS40 overexpression have shown promise in preclinical models, ameliorating pathological cardiac hypertrophy by reducing protein synthesis and without impairing physiological growth. Similarly, strategies modulating signaling, such as through myocyte-enriched calcineurin-interacting protein (MCIP1) delivery, block hypertrophic in response to stress signals, offering potential for targeted intervention in models. (HDAC) inhibitors, like those targeting HDAC5, are under investigation for their role in reversing vascular and cardiac hypertrophy by altering epigenetic regulation of pro-hypertrophic genes, with preclinical studies from the early demonstrating reduced myocyte size and in angiotensin II-induced models. As of 2025, recent preclinical research has highlighted HDAC6 inhibitors for preventing pathological cardiac hypertrophy and HDAC2 down-regulation for mitigating ventricular arrhythmias in pressure overload models. Clinical trials in the have explored HDAC inhibitors primarily in but are expanding to cardiovascular applications, showing anti-fibrotic effects in related inflammatory conditions. Prognosis in hypertrophy-related conditions improves markedly with early intervention, particularly through control to halt progression to . Intensive systolic lowering to below 120 mmHg reduces the incidence of new LVH by up to 25-30% and slows progression in existing cases, as demonstrated in large trials like SPRINT. In patients with malignant LVH, such strategies prevent and mortality, yielding absolute risk reductions of approximately 2-5% over standard care. Overall, timely management via antihypertensives and lifestyle changes can decrease cardiovascular event risk by 40-60% in hypertensive LVH cohorts, underscoring the value of proactive therapy.

References

  1. https://pmc.ncbi.nlm.nih.gov/articles/PMC10625844/
  2. https://pmc.ncbi.nlm.nih.gov/articles/PMC8075408/
  3. https://www.ncbi.nlm.nih.gov/books/NBK557575/
  4. https://pmc.ncbi.nlm.nih.gov/articles/PMC4575564/
  5. https://www.mayoclinic.org/diseases-conditions/left-ventricular-hypertrophy/symptoms-causes/syc-20374314
  6. https://www.mayoclinic.org/diseases-conditions/hypertrophic-cardiomyopathy/symptoms-causes/syc-20350198
  7. https://pmc.ncbi.nlm.nih.gov/articles/PMC10121965/
  8. https://pmc.ncbi.nlm.nih.gov/articles/PMC6423469/
  9. https://hekint.org/2017/01/29/rudolf-virchow-pathologist-anthropologist-and-social-thinker/
  10. https://www.nature.com/articles/s41467-020-20123-1
  11. https://pmc.ncbi.nlm.nih.gov/articles/PMC5352916/
  12. https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/organ-weight
  13. https://pmc.ncbi.nlm.nih.gov/articles/PMC7171462/
  14. https://pubmed.ncbi.nlm.nih.gov/19325873/
  15. https://pmc.ncbi.nlm.nih.gov/articles/PMC3529336/
  16. https://pmc.ncbi.nlm.nih.gov/articles/PMC5998678/
  17. https://www.ncbi.nlm.nih.gov/books/NBK559304/
  18. https://pmc.ncbi.nlm.nih.gov/articles/PMC3561756/
  19. https://pmc.ncbi.nlm.nih.gov/articles/PMC10587333/
  20. https://www.healthline.com/health/how-long-does-it-take-to-lose-muscle-mass
  21. https://pmc.ncbi.nlm.nih.gov/articles/PMC7099858/
  22. https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1179834/full
  23. https://pmc.ncbi.nlm.nih.gov/articles/PMC3458709/
  24. https://pubmed.ncbi.nlm.nih.gov/27262674/
  25. https://pmc.ncbi.nlm.nih.gov/articles/PMC6489905/
  26. https://www.ahajournals.org/doi/10.1161/circinterventions.111.962795
  27. https://jag.journalagent.com/z4/download_fulltext.asp?pdir=ejm&plng=tur&un=EJM-27247
  28. https://onlinelibrary.wiley.com/doi/full/10.1002/jcsm.13468
  29. https://www.nature.com/articles/ncb1101-1014
  30. https://pubmed.ncbi.nlm.nih.gov/23517348/
  31. https://pubmed.ncbi.nlm.nih.gov/11715023/
  32. https://pubmed.ncbi.nlm.nih.gov/9568714/
  33. https://pubmed.ncbi.nlm.nih.gov/10448862/
  34. https://pubmed.ncbi.nlm.nih.gov/11101507/
  35. https://pubmed.ncbi.nlm.nih.gov/15276472/
  36. https://pubmed.ncbi.nlm.nih.gov/20847704/
  37. https://rupress.org/jcb/article/156/4/751/32641/Different-modes-of-hypertrophy-in-skeletal-muscle
  38. https://pubmed.ncbi.nlm.nih.gov/31314585/
  39. https://journals.physiology.org/doi/full/10.1152/japplphysiol.00685.2018
  40. https://rpstrength.com/blogs/articles/ab-hypertrophy-training-tips
  41. https://pubmed.ncbi.nlm.nih.gov/15075918/
  42. https://pmc.ncbi.nlm.nih.gov/articles/PMC7372125/
  43. https://pubmed.ncbi.nlm.nih.gov/35389932/
  44. https://www.jci.org/articles/view/69830
  45. https://pmc.ncbi.nlm.nih.gov/articles/PMC2300466/
  46. https://pubmed.ncbi.nlm.nih.gov/12746273/
  47. https://pubmed.ncbi.nlm.nih.gov/19566828/
  48. https://pubmed.ncbi.nlm.nih.gov/10368127/
  49. https://www.jacc.org/doi/10.1016/j.jacc.2010.09.040
  50. https://academic.oup.com/ajh/article/21/5/500/187625
  51. https://www.ahajournals.org/doi/10.1161/01.CIR.102.4.470
  52. https://www.ncbi.nlm.nih.gov/books/NBK557534/
  53. https://pmc.ncbi.nlm.nih.gov/articles/PMC3036484/
  54. https://pmc.ncbi.nlm.nih.gov/articles/PMC7017496/
  55. https://pmc.ncbi.nlm.nih.gov/articles/PMC7332829/
  56. https://pmc.ncbi.nlm.nih.gov/articles/PMC5898826/
  57. https://pmc.ncbi.nlm.nih.gov/articles/PMC3179830/
  58. https://www.ncbi.nlm.nih.gov/books/NBK558920/
  59. https://pmc.ncbi.nlm.nih.gov/articles/PMC3074887/
  60. https://pmc.ncbi.nlm.nih.gov/articles/PMC6346828/
  61. https://www.ahajournals.org/doi/10.1161/CIR.0000000000000937
  62. https://pmc.ncbi.nlm.nih.gov/articles/PMC7786033/
  63. https://www.ahajournals.org/doi/10.1161/JAHA.122.027618
  64. https://www.sciencedirect.com/science/article/abs/pii/S0167527316309354
  65. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243163
  66. https://pmc.ncbi.nlm.nih.gov/articles/PMC4040877/
  67. https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.1026884/full
  68. https://pmc.ncbi.nlm.nih.gov/articles/PMC2464755/
  69. https://www.ahajournals.org/doi/10.1161/hc3901.096700
  70. https://www.nature.com/articles/s41440-024-01634-6
  71. https://pmc.ncbi.nlm.nih.gov/articles/PMC1909123/
  72. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0027294
  73. https://www.ahajournals.org/doi/10.1161/hypertensionaha.106.079426
  74. https://pmc.ncbi.nlm.nih.gov/articles/PMC3732982/
  75. https://www.pnas.org/doi/10.1073/pnas.041614798
  76. https://journals.physiology.org/doi/full/10.1152/ajpheart.00683.2020?doi=10.1152/ajpheart.00683.2020
  77. https://pmc.ncbi.nlm.nih.gov/articles/PMC12429223/
  78. https://academic.oup.com/cardiovascres/article/121/3/424/7984767
  79. https://pmc.ncbi.nlm.nih.gov/articles/PMC4742605/
  80. https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.122.20732
  81. https://www.sciencedirect.com/science/article/pii/S0735109722065585
  82. https://pmc.ncbi.nlm.nih.gov/articles/PMC5538944/
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