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Medicine and Science in Sports and... Sep 2022Skeletal muscle plays a critical role in physical function and metabolic health. Muscle is a highly adaptable tissue that responds to resistance exercise (RE; loading)... (Review)
Review
Skeletal muscle plays a critical role in physical function and metabolic health. Muscle is a highly adaptable tissue that responds to resistance exercise (RE; loading) by hypertrophying, or during muscle disuse, RE mitigates muscle loss. Resistance exercise training (RET)-induced skeletal muscle hypertrophy is a product of external (e.g., RE programming, diet, some supplements) and internal variables (e.g., mechanotransduction, ribosomes, gene expression, satellite cells activity). RE is undeniably the most potent nonpharmacological external variable to stimulate the activation/suppression of internal variables linked to muscular hypertrophy or countering disuse-induced muscle loss. Here, we posit that despite considerable research on the impact of external variables on RET and hypertrophy, internal variables (i.e., inherent skeletal muscle biology) are dominant in regulating the extent of hypertrophy in response to external stimuli. Thus, identifying the key internal skeletal muscle-derived variables that mediate the translation of external RE variables will be pivotal to determining the most effective strategies for skeletal muscle hypertrophy in healthy persons. Such work will aid in enhancing function in clinical populations, slowing functional decline, and promoting physical mobility. We provide up-to-date, evidence-based perspectives of the mechanisms regulating RET-induced skeletal muscle hypertrophy.
Topics: Exercise; Humans; Hypertrophy; Mechanotransduction, Cellular; Muscle, Skeletal; Resistance Training
PubMed: 35389932
DOI: 10.1249/MSS.0000000000002929 -
Canadian Journal of Physiology and... Feb 2020The heart is capable of responding to stressful situations by increasing muscle mass, which is broadly defined as cardiac hypertrophy. This phenomenon minimizes... (Review)
Review
The heart is capable of responding to stressful situations by increasing muscle mass, which is broadly defined as cardiac hypertrophy. This phenomenon minimizes ventricular wall stress for the heart undergoing a greater than normal workload. At initial stages, cardiac hypertrophy is associated with normal or enhanced cardiac function and is considered to be adaptive or physiological; however, at later stages, if the stimulus is not removed, it is associated with contractile dysfunction and is termed as pathological cardiac hypertrophy. It is during physiological cardiac hypertrophy where the function of subcellular organelles, including the sarcolemma, sarcoplasmic reticulum, mitochondria, and myofibrils, may be upregulated, while pathological cardiac hypertrophy is associated with downregulation of these subcellular activities. The transition of physiological cardiac hypertrophy to pathological cardiac hypertrophy may be due to the reduction in blood supply to hypertrophied myocardium as a consequence of reduced capillary density. Oxidative stress, inflammatory processes, Ca-handling abnormalities, and apoptosis in cardiomyocytes are suggested to play a critical role in the depression of contractile function during the development of pathological hypertrophy.
Topics: Animals; Apoptosis; Calcium; Cardiomegaly; Cytokines; Humans; Intracellular Space
PubMed: 31815523
DOI: 10.1139/cjpp-2019-0566 -
Nephrology (Carlton, Vic.) Dec 2019Following surgical removal of one kidney, the other enlarges and increases its function. The mechanism for the sensing of this change and the growth is incompletely... (Review)
Review
Following surgical removal of one kidney, the other enlarges and increases its function. The mechanism for the sensing of this change and the growth is incompletely understood but begins within days and compensatory renal hypertrophy (CRH) is the dominant contributor to the growth. In many individuals undergoing nephrectomy for cancer or kidney donation this produces a substantial and helpful increase in renal function. Two main mechanisms have been proposed, one in which increased activity by the remaining kidney leads to hypertrophy, the second in which there is release of a kidney specific factor in response to a unilateral nephrectomy that initiates CRH. Whilst multiple growth factors and pathways such as the mTORC pathway have been implicated in experimental studies, their roles and the precise mechanism of CRH are not defined. Unrestrained hypoxia inducible factor activation in renal cancer promotes growth and may play an important role in driving CRH.
Topics: Adaptation, Physiological; Animals; Cell Enlargement; Cell Proliferation; Humans; Hypertrophy; Kidney; Nephrectomy; Organ Size; Postoperative Period
PubMed: 30809888
DOI: 10.1111/nep.13578 -
Journal of Clinical Hypertension... Apr 2017Systemic hypertension and physical exercise are both associated with cardiac adaptations. The impact is most prominent on the left side of the heart, which hypertrophies... (Review)
Review
Systemic hypertension and physical exercise are both associated with cardiac adaptations. The impact is most prominent on the left side of the heart, which hypertrophies leading to left ventricular hypertrophy. This article reviews structural and functional cardiac changes seen in hypertensive and athlete's hearts.
Topics: Athletes; Exercise; Humans; Hypertension; Hypertrophy, Left Ventricular
PubMed: 28247560
DOI: 10.1111/jch.12977 -
Anatomy and Embryology 1990Smooth muscles of viscera undergo a large increase in volume when there is a chronic, partial obstruction impairing the flow of lumenal contents. Hypertrophy of smooth... (Review)
Review
Smooth muscles of viscera undergo a large increase in volume when there is a chronic, partial obstruction impairing the flow of lumenal contents. Hypertrophy of smooth muscle occurs in various medical conditions and several methods are available for inducing it experimentally in laboratory animals, especially in urinary bladder, small intestine and ureter. The hypertrophic response differs somewhat with the type of organ, the animal species, the age of the subject, and the experimental procedure. Ten- to fifteen-fold increases in muscle volume develop within a few weeks in the urinary bladder or the ileum of adult animals, a growth that would not have occurred in the lifespan of the animal without the experimental intervention. The general architecture of the muscle and the boundaries with adjacent tissues are well preserved. In intestinal hypertrophy, muscle cells increase in number: mitoses are found in mature, fully differentiated muscle cells. Cell division by full longitudinal splitting of muscle cells may also occur. Enlargement of muscle cells accounts for most of the muscle hypertrophy. The hypertrophic muscle cell has an irregular profile with deep indentations of the cell membrane, bearing caveolae and dense bands; however, the cell surface grows less than the cell volume (reduction of surface-to-volume ratio). The nucleus is crenated and is much less enlarged than the cell (reduction of the nucleo-plasmatic ratio). Mitochondria grow in number but in some muscles their spatial density decreases; intermediate filaments increase more than myofilaments. The spatial density of sarcoplasmic reticulum is generally increased. In the hypertrophic intestine, gap junctions increase in number and size; in the bladder, gap junctions are absent both in control and in hypertrophy. Thus the hypertrophic muscle cell is not only larger than a control cell, but has a different pattern of its structural components. Extensive neo-angiogenesis maintains a good blood supply to the hypertrophic muscle. The density of innervation is much decreased in the hypertrophic intestine, whereas it appears well maintained in the bladder. Neuronal enlargement is found in the intramural ganglia of the intestine and in the pelvic ganglion. The mechanisms involved in hypertrophic growth are unknown. Three possible factors, mechanical factors, especially stretch, altered nerve discharge, and trophic factors are discussed.
Topics: Animals; Humans; Hypertrophy; Muscle, Smooth; Viscera
PubMed: 2291488
DOI: 10.1007/BF00178906 -
Circulation Journal : Official Journal... 2016Left ventricular hypertrophy (LVH) is growth in left ventricular mass caused by increased cardiomyocyte size. LVH can be a physiological adaptation to strenuous physical... (Review)
Review
Left ventricular hypertrophy (LVH) is growth in left ventricular mass caused by increased cardiomyocyte size. LVH can be a physiological adaptation to strenuous physical exercise, as in athletes, or it can be a pathological condition, which is either genetic or secondary to LV overload. Physiological LVH is usually benign and regresses upon reduction/cessation of physical activity. Pathological LVH is a compensatory phenomenon, which eventually may become maladaptive and evolve towards progressive LV dysfunction and heart failure (HF). Both interstitial and replacement fibrosis play a major role in the progressive decompensation of the hypertrophied LV. Coronary microvascular dysfunction (CMD) and myocardial ischemia, which have been demonstrated in most forms of pathological LVH, have an important pathogenetic role in the formation of replacement fibrosis and both contribute to the evolution towards LV dysfunction and HF. Noninvasive imaging allows detection of myocardial fibrosis and CMD, thus providing unique information for the stratification of patients with LVH. (Circ J 2016; 80: 555-564).
Topics: Fibrosis; Heart Failure; Humans; Hypertrophy, Left Ventricular; Ventricular Dysfunction, Left
PubMed: 26853555
DOI: 10.1253/circj.CJ-16-0062 -
American Heart Journal Jul 1991Major advances in left ventricular hypertrophy (LVH) and hypertension have occurred in recent years. The ability to diagnose LVH has been improved by echocardiography,... (Review)
Review
Major advances in left ventricular hypertrophy (LVH) and hypertension have occurred in recent years. The ability to diagnose LVH has been improved by echocardiography, and with this technique it has been shown that evidence of LVH is an important independent risk factor for cardiovascular disease. The major cause of death in patients with hypertension and LVH is coronary artery disease. Therefore an understanding of the interrelationships between these two disorders is fundamental, and it is now clear that the hypertrophied ventricle is vulnerable to myocardial ischemia. Appreciation of the mechanisms of sudden death has also increased, although the exact situation in patients with LVH remains to be clarified. Regression of LVH is known to occur with the use of several different antihypertensive drugs. Recent studies indicate that the calcium blocking agent nicardipine, in addition to beta-blocking drugs and angiotensin-converting enzyme inhibitors, brings about LVH regression without any deterioration of left ventricular function. However, further studies are needed to assess the long-term benefits of this regression.
Topics: Calcium Channel Blockers; Cardiomegaly; Coronary Disease; Death, Sudden; Echocardiography; Humans; Hypertension; Remission Induction
PubMed: 1828935
DOI: 10.1016/0002-8703(91)90840-e -
Circulation Jun 1991Left ventricular hypertrophy (LVH) is the major risk factor associated with myocardial failure. An explanation for why a presumptive adaptation such as LVH would prove... (Review)
Review
Left ventricular hypertrophy (LVH) is the major risk factor associated with myocardial failure. An explanation for why a presumptive adaptation such as LVH would prove pathological has been elusive. Insights into the impairment in contractility of the hypertrophied myocardium have been sought in the biochemistry of cardiac myocyte contraction. Equally compelling is a consideration of abnormalities in myocardial structure that impair organ contractile function while preserving myocyte contractility. For example, in the LVH that accompanies hypertension, the extracellular space is frequently the site of an abnormal accumulation of fibrillar collagen. This reactive and progressive interstitial and perivascular fibrosis accounts for abnormal myocardial stiffness and ultimately ventricular dysfunction and is likely a result of cardiac fibroblast growth and enhanced collagen synthesis. The disproportionate involvement of this nonmyocyte cell, however, is not a uniform accompaniment to myocyte hypertrophy and LVH, suggesting that the growth of myocyte and nonmyocyte cells is independent of each other. This has now been demonstrated in in vivo studies of experimental hypertension in which the abnormal fibrous tissue response was found in the hypertensive, hypertrophied left ventricle as well as in the normotensive, nonhypertrophied right ventricle. These findings further suggest that a circulating substance that gained access to the common coronary circulation of the ventricles was involved. This hypothesis has been tested in various animal models in which plasma concentrations of angiotensin II and aldosterone were varied. Based on morphometric and morphological findings, it can be concluded that arterial hypertension (i.e., an elevation in coronary perfusion pressure) together with elevated circulating aldosterone are associated with cardiac fibroblast involvement and the resultant heterogeneity in tissue structure. Nonmyocyte cells of the cardiac interstitium represent an important determinant of pathological LVH. The mechanisms that invoke short- (e.g., collagen metabolism) and long-term (e.g., mitosis) responses of cardiac fibroblasts require further investigation and integration of in vitro with in vivo studies. The stage is set, however, to prevent pathological LVH resulting from myocardial fibrosis as well as to reverse it.
Topics: Aldosterone; Animals; Cardiomegaly; Fibrosis; Humans; Hypertension; Models, Cardiovascular; Myocardium; Renin-Angiotensin System
PubMed: 1828192
DOI: 10.1161/01.cir.83.6.1849 -
Heart Failure Reviews Sep 2013Normal cardiac function requires high and continuous supply with ATP. As mitochondria are the major source of ATP production, it is apparent that mitochondrial function... (Review)
Review
Normal cardiac function requires high and continuous supply with ATP. As mitochondria are the major source of ATP production, it is apparent that mitochondrial function and cardiac function need to be closely related to each other. When subjected to overload, the heart hypertrophies. Initially, the development of hypertrophy is a compensatory mechanism, and contractile function is maintained. However, when the heart is excessively and/or persistently stressed, cardiac function may deteriorate, leading to the onset of heart failure. There is considerable evidence that alterations in mitochondrial function are involved in the decompensation of cardiac hypertrophy. Here, we review metabolic changes occurring at the mitochondrial level during the development of cardiac hypertrophy and the transition to heart failure. We will focus on changes in mitochondrial substrate metabolism, the electron transport chain and the role of oxidative stress. We will demonstrate that, with respect to mitochondrial adaptations, a clear distinction between hypertrophy and heart failure cannot be made because most of the findings present in overt heart failure can already be found in the various stages of hypertrophy.
Topics: Animals; Cardiomegaly; Heart Failure; Humans; Mitochondria, Heart; Oxidative Stress
PubMed: 22968404
DOI: 10.1007/s10741-012-9346-7 -
Current Hypertension Reports Dec 2004Cardiac hypertrophy is a response to long-term pathologic (eg, hypertension) or physiologic (eg, exercise) hemodynamic overload accompanied by changes in energy... (Review)
Review
Cardiac hypertrophy is a response to long-term pathologic (eg, hypertension) or physiologic (eg, exercise) hemodynamic overload accompanied by changes in energy substrate utilization. The pattern of substrate utilization (or metabolic phenotype) differs dramatically between pathologic and physiologic cardiac hypertrophy with directionally opposite changes in oxidation of fatty acids and glucose and glycolysis. These findings indicate that the metabolic response to long-term alterations in hemodynamic workload is not stereotypical, but is influenced by the nature of the stimulus leading to cardiac hypertrophy. Although the changes in substrate utilization are adaptive, in the case of pathologic stimuli, the changes in metabolism interfere with functional resiliency of the heart to metabolic stress, as occurs during ischemia-reperfusion. The distinct metabolic phenotypes of hearts hypertrophied in response to pathologic or physiologic stimuli are due not only to alteration in expression of metabolic enzymes and proteins, but also to post-translational modulation of metabolic enzymes and proteins.
Topics: Cardiomegaly; Energy Metabolism; Humans; Phenotype
PubMed: 15527686
DOI: 10.1007/s11906-004-0036-2