Exercise-Induced Cardiac Remodeling

doi:10.1016/j.pcad.2012.01.006

Progress in Cardiovascular Diseases

Volume 54, Issue 5, March–April 2012, Pages 380-386

https://doi.org/10.1016/j.pcad.2012.01.006 Get rights and content

Abstract

Early investigations in the late 1890s and early 1900s documented cardiac enlargement in athletes with above-normal exercise capacity and no evidence of cardiovascular disease. Such findings have been reported for more than a century and continue to intrigue scientists and clinicians. It is well recognized that repetitive participation in vigorous physical exercise results in significant changes in myocardial structure and function. This process, termed exercise-induced cardiac remodeling (EICR), is characterized by structural cardiac changes including left ventricular hypertrophy with sport-specific geometry (eccentric vs concentric). Associated alterations in both systolic and diastolic functions are emerging as recognized components of EICR. The increasing popularity of recreational exercise and competitive athletics has led to a growing number of individuals exhibiting these findings in routine clinical practice. This review will provide an overview of EICR in athletes.

Section snippets

Overview of relevant exercise physiology

All forms of exercise require an increase in skeletal muscle work. There is a direct relationship between exercise intensity (external work) and the body's demand for oxygen. The oxygen demand during exercise is met by increasing pulmonary oxygen uptake (Vo₂). In addition, the cardiovascular system is responsible for transporting oxygen-rich blood from the lungs to the skeletal muscles, a process quantified as cardiac output (in liters per minute). Exercise-induced cardiac remodeling enhances

Determinants of EICR magnitude

The extent of EICR varies considerably across individual athletes. Obvious explanatory factors including sport-type, prior exercise exposure, and training-intensity/duration do not explain all of this variability.⁴⁷ Additional factors including sex, ethnicity, and genetics are contributory. Available data suggest that female athletes exhibit quantitatively less physiologic remodeling than their male counterparts.44, 48, 49, 50, 51, 52, 53 This appears to be true even when cardiac dimensions are

Cellular mechanisms of EICR

The cellular pathways responsible for EICR remain poorly understood. There are currently no mechanistic studies in humans that explain why the myocardial cells remodel in the face of repeated exercise bouts. The lack of in vivo data relates to the numerous challenges, most notably, the acquisition of cardiac tissue from healthy subjects, inherent in study design. However, animal data examining pathologic forms of ventricular hypertrophy during experimental exercise intervention may be

EICR: adaptive physiology vs pathologic myopathy

The significance of cardiac enlargement in athletes has been debated since the time of its initial description. Although EICR is most often regarded as a beneficial adaptation to exercise, this view has not been universally accepted. It was postulated as early as 1902 that cardiac enlargement in athletes is a form of overuse pathology and that prolonged participation in sport could lead to premature cardiovascular system collapse.⁶³ This concept has resurfaced numerous times over the last

Conclusions

Participation in vigorous recreational exercise and competitive athletics continues to gain popularity worldwide because of factors including the documented health benefits of regular physical exercise, increasing availability of community-based athletic programs, and growing numbers of open-enrollment sport events (ie, community-based road running races). This increasing sport participation will be paralleled by increases in the number of people with features of EICR. The practicing

Statement of Conflict of Interest

The authors declare that there are no conflicts of interest.

References (72)

B.J. Maron et al.
Introduction: eligibility recommendations for competitive athletes with cardiovascular abnormalities—general considerations
J Am Coll Cardiol
(2005)
S. Sharma et al.
Physiologic limits of left ventricular hypertrophy in elite junior athletes: relevance to differential diagnosis of athlete's heart and hypertrophic cardiomyopathy
J Am Coll Cardiol
(2002)
E.Z. Fisman et al.
Effect of intensive resistance training on isotonic exercise Doppler indexes of left ventricular systolic function
Am J Cardiol
(2002)
P.S. Douglas et al.
Left ventricular structure and function by echocardiography in ultraendurance athletes
Am J Cardiol
(1986)
C.A. Gilbert et al.
Echocardiographic study of cardiac dimensions and function in the endurance-trained athlete
Am J Cardiol
(1977)
E. Abergel et al.
Serial left ventricular adaptations in world-class professional cyclists: implications for disease screening and follow-up
J Am Coll Cardiol
(2004)
V. Richand et al.
An ultrasound speckle tracking (two-dimensional strain) analysis of myocardial deformation in professional soccer players compared with healthy subjects and hypertrophic cardiomyopathy
Am J Cardiol
(2007)
N. Cardim et al.
Doppler tissue imaging: regional myocardial function in hypertrophic cardiomyopathy and in athlete's heart
J Am Soc Echocardiogr
(2003)
R.B. Weiner et al.
The impact of endurance exercise training on left ventricular torsion
JACC Cardiovasc Imaging
(2010)
P. Caso et al.
Pulsed Doppler tissue imaging in endurance athletes: relation between left ventricular preload and myocardial regional diastolic function
Am J Cardiol
(2000)

A. Prasad et al.

The effects of aging and physical activity on Doppler measures of diastolic function

Am J Cardiol

(2007)

A. D'Andrea et al.

Left ventricular myocardial velocities and deformation indexes in top-level athletes

J Am Soc Echocardiogr

(2010)

A.M. Hauser et al.

Symmetric cardiac enlargement in highly trained endurance athletes: a two-dimensional echocardiographic study

Am Heart J

(1985)

J. Scharhag et al.

Athlete's heart: right and left ventricular mass and function in male endurance athletes and untrained individuals determined by magnetic resonance imaging

J Am Coll Cardiol

(2002)

J.H. Kim et al.

Significance of electrocardiographic right bundle branch block in trained athletes

Am J Cardiol

(2011)

M. Scharf et al.

Cardiac magnetic resonance assessment of left and right ventricular morphologic and functional adaptations in professional soccer players

Am Heart J

(2010)

A. Pelliccia et al.

Prevalence and clinical significance of left atrial remodeling in competitive athletes

J Am Coll Cardiol

(2005)

A. D'Andrea et al.

Left atrial volume index in highly trained athletes

Am Heart J

(2010)

M. Wilhelm et al.

Atrial remodeling, autonomic tone, and lifetime training hours in nonelite athletes

Am J Cardiol

(2011)

T. Rowland et al.

Influence of sex on the “Athlete's Heart” in trained cyclists

J Sci Med Sport

(2010)

S. Basavarajaiah et al.

Ethnic differences in left ventricular remodeling in highly-trained athletes relevance to differentiating physiologic left ventricular hypertrophy from hypertrophic cardiomyopathy

J Am Coll Cardiol

(2008)

J. Karjalainen et al.

Angiotensinogen gene M235T polymorphism predicts left ventricular hypertrophy in endurance athletes

J Am Coll Cardiol

(1999)

A.L. Baggish et al.

Impact of family hypertension history on exercise-induced cardiac remodeling

Am J Cardiol

(2009)

R.W. Harper et al.

Exercise-induced right ventricular dysplasia/cardiomyopathy–an emerging condition distinct from arrhythmogenic right ventricular dysplasia/cardiomyopathy

Heart Lung Circ

(2009)

A. Pelliccia et al.

Long-term clinical consequences of intense, uninterrupted endurance training in olympic athletes

J Am Coll Cardiol

(2010)

S. Henschen

Skidlauf und Skidwettlauf. Eine medizinische Sportstudie

Mitt Med Klin Upsala

(1899)

E.A. Darling

The effects of training. A study of the Harvard University crews

Boston Med Surg J

(1899)

H. Roskamm et al.

Relations between heart size and physical efficiency in male and female athletes in comparison with normal male and female subjects

Arch Kreislaufforsch

(1961)

H. Reindell et al.

The heart and blood circulation in athletes

Med Welt

(1960)

V.V. Bulychev et al.

Roentgenological and instrumental examination of the heart in athletes

Klin Med

(1965)

L.B. Rowell

Human circulation: regulation during physical stress

(1986)

A.D. Jose et al.

The normal range and determinants of the intrinsic heart rate in man

Cardiovasc Res

(1970)

A.L. Uusitalo et al.

Exhaustive endurance training for 6-9 weeks did not induce changes in intrinsic heart rate and cardiac autonomic modulation in female athletes

Int J Sports Med

(1998)

W.R. Roeske et al.

Noninvasive evaluation of ventricular hypertrophy in professional athletes

Circulation

(1976)

A. Pelliccia et al.

Physiologic left ventricular cavity dilatation in elite athletes

Ann Intern Med

(1999)

A. Pelliccia et al.

The upper limit of physiologic cardiac hypertrophy in highly trained elite athletes

N Engl J Med

(1991)

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The athlete's heart is a well-known phenomenon characterized by a harmonic remodelling that affects the cardiac chambers. However, whether mild-to-moderate aortic dilatation can be considered normal in athletes is debated. This study aimed to evaluate the ratio between left ventricular (LV) size and aortic dimensions, reporting the normal values of the ratio between the aortic root diameters at the level of the sinuses of Valsalva and LV diameters (AoD/LVEDD ratio) in a wide cohort of competitive athletes.
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Citation Excerpt :
The positive effects of physical exercise in suppressing cardiac hypertrophy and improving cardiac function have been documented in patients with heart failure.10,11 Exercise could directly trigger intrinsic myocardial changes, including increased cytosolic antioxidant capacity, mitochondrial biogenesis, and cardioprotective cardiac growth, by activating signaling pathways, such as insulin-like growth factor 1/ Phosphatidylinositol 3-kinase/protein kinase B (IGF1/PI3K/Akt) pathway,12,13 and modulating gene expression via microRNAs (miR-17-3p, miR-222, etc.),14–17 which promote physiological cardiac remodeling and resist pathological remodeling.18–20 Exercise also orchestrates multisystemic effects, such as cardiovascular adaptions, by provoking the muscle and other tissues to exert endocrine effects and release various signaling molecules named “exerkines” into the circulation.21–23
Exercise training protects the heart against pathological cardiac remodeling and confers cardioprotection from heart failure. However, the underlying mechanism is still elusive.
An integrative analysis of multi-omics data of the skeletal muscle in response to exercise is performed to search for potential exerkine. Then, CCDC80tide is examined in humans after acute exercise. The role of CCDC80tide is assessed in a mouse model of hypertensive cardiac remodeling and in hypertension-mediated cell injury models. The transcriptomic analysis and immunoprecipitation assay are conducted to explore the mechanism.
The coiled-coil domain-containing protein 80 (CCDC80) is found strongly positively associated with exercise. Interestingly, exercise stimuli induce the secretion of C-terminal CCDC80 (referred as CCDC80tide hereafter) via EVs-encapsulated CCDC80tide into the circulation. Importantly, cardiac-specific expression of CCDC80tide protects against angiotensin II (Ang II)-induced cardiac hypertrophy and fibrosis in mice. In in vitro studies, the expression of CCDC80tide reduces Ang II-induced cardiomyocyte hypertrophy, cardiac microvascular endothelial cell (CMEC) inflammation, and mitigated vascular smooth muscle cell (VSMC) proliferation and collagen formation. To understand the cardioprotective effect of CCDC80tide, a transcriptomic analysis reveals a dramatic inhibition of the STAT3 (Signal transducer and activator of transcription 3) signaling pathway in CCDC80tide overexpressing cells. Mechanistically, CCDC80tide selectively interacts with the kinase-active form of JAK2 (Janus kinase 2) and consequently inhibits its kinase activity to phosphorylate and activate STAT3.
The results provide new insights into exercise-afforded cardioprotection in pathological cardiac remodeling and highlight the therapeutic potential of CCDC80tide in heart failure treatment.
This work was supported by the National Natural Science Foundation of China [Grant/Award Numbers: 81770428, 81830010, 82130012, 81900438, 82100447); Shanghai Science and Technology Committee [Grant/Award Numbers: 21S11903000, 19JC1415702]; Emerging and Advanced Technology Programs of Hospital Development Center of Shanghai [Grant/Award Number: SHDC12018129]; China Postdoctoral Science Foundation [2021M692108]; and China National Postdoctoral Program for Innovative Talents [BX20200211].
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View all citing articles on Scopus

: Statement of Conflict of Interest. See page 384.

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Exercise-Induced Cardiac Remodeling

Abstract

Section snippets

Overview of relevant exercise physiology

Determinants of EICR magnitude

Cellular mechanisms of EICR

EICR: adaptive physiology vs pathologic myopathy

Conclusions

Statement of Conflict of Interest

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

Am J Cardiol

Am J Cardiol

J Am Coll Cardiol

Am J Cardiol

J Am Soc Echocardiogr

JACC Cardiovasc Imaging

Am J Cardiol

Am J Cardiol

J Am Soc Echocardiogr

Am Heart J

J Am Coll Cardiol

Am J Cardiol

Am Heart J

J Am Coll Cardiol

Am Heart J

Am J Cardiol

J Sci Med Sport

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

Heart Lung Circ

J Am Coll Cardiol

Skidlauf und Skidwettlauf. Eine medizinische Sportstudie

Mitt Med Klin Upsala

The effects of training. A study of the Harvard University crews

Boston Med Surg J

Relations between heart size and physical efficiency in male and female athletes in comparison with normal male and female subjects

Arch Kreislaufforsch

The heart and blood circulation in athletes

Med Welt

Roentgenological and instrumental examination of the heart in athletes

Klin Med

Human circulation: regulation during physical stress

The normal range and determinants of the intrinsic heart rate in man

Cardiovasc Res

Exhaustive endurance training for 6-9 weeks did not induce changes in intrinsic heart rate and cardiac autonomic modulation in female athletes

Int J Sports Med

Noninvasive evaluation of ventricular hypertrophy in professional athletes

Circulation

Physiologic left ventricular cavity dilatation in elite athletes

Ann Intern Med

The upper limit of physiologic cardiac hypertrophy in highly trained elite athletes

N Engl J Med