The young mouse heart is composed of myocytes heterogeneous in age and function

Marcello Rota, Toru Hosoda, Antonella De Angelis, Michael L. Arcarese, Grazia Esposito, Roberto Rizzi, Jochen Tillmanns, Derin Tugal, Ezio Musso, Ornella Rimoldi, Claudia Bearzi, Konrad Urbanek, Piero Anversa, Annarosa Leri, Jan Kajstura

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

The recognition that the adult heart continuously renews its myocyte compartment raises the possibility that the age and lifespan of myocytes does not coincide with the age and lifespan of the organ and organism. If this were the case, myocyte turnover would result at any age in a myocardium composed by a heterogeneous population of parenchymal cells which are structurally integrated but may contribute differently to myocardial performance. To test this hypothesis, left ventricular myocytes were isolated from mice at 3 months of age and the contractile, electrical, and calcium cycling characteristics of these cells were determined together with the expression of the senescence-associated protein p16 and telomere length. The heart was characterized by the coexistence of young, aged, and senescent myocytes. Old nonreplicating, p16-positive, hypertrophied myocytes with severe telomeric shortening were present together with young, dividing, p16-negative, small myocytes with long telomeres. A class of myocytes with intermediate properties was also found. Physiologically, evidence was obtained in favor of the critical role that action potential (AP) duration and ICaL play in potentiating Ca cycling and the mechanical behavior of young myocytes or in decreasing Ca transients and the performance of senescent hypertrophied cells. The characteristics of the AP appeared to be modulated by the transient outward K current Ito which was influenced by the different expression of the K channels subunits. Collectively, these observations at the physiological and structural cellular level document that by necessity the heart has to constantly repopulate its myocyte compartment to replace senescent poorly contracting myocytes with younger more efficient cells. Thus, cardiac homeostasis and myocyte turnover regulate cardiac function.

Original languageEnglish
Pages (from-to)387-399
Number of pages13
JournalCirculation Research
Volume101
Issue number4
DOIs
Publication statusPublished - Aug 2007

Fingerprint

Muscle Cells
Telomere
Action Potentials
Cardiac Myocytes
Myocardium
Homeostasis
Calcium

Keywords

  • Action potential profile
  • Excitation-contraction coupling
  • Myocyte volume
  • Senescence-associated proteins
  • Telomere length

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Rota, M., Hosoda, T., De Angelis, A., Arcarese, M. L., Esposito, G., Rizzi, R., ... Kajstura, J. (2007). The young mouse heart is composed of myocytes heterogeneous in age and function. Circulation Research, 101(4), 387-399. https://doi.org/10.1161/CIRCRESAHA.107.151449

The young mouse heart is composed of myocytes heterogeneous in age and function. / Rota, Marcello; Hosoda, Toru; De Angelis, Antonella; Arcarese, Michael L.; Esposito, Grazia; Rizzi, Roberto; Tillmanns, Jochen; Tugal, Derin; Musso, Ezio; Rimoldi, Ornella; Bearzi, Claudia; Urbanek, Konrad; Anversa, Piero; Leri, Annarosa; Kajstura, Jan.

In: Circulation Research, Vol. 101, No. 4, 08.2007, p. 387-399.

Research output: Contribution to journalArticle

Rota, M, Hosoda, T, De Angelis, A, Arcarese, ML, Esposito, G, Rizzi, R, Tillmanns, J, Tugal, D, Musso, E, Rimoldi, O, Bearzi, C, Urbanek, K, Anversa, P, Leri, A & Kajstura, J 2007, 'The young mouse heart is composed of myocytes heterogeneous in age and function', Circulation Research, vol. 101, no. 4, pp. 387-399. https://doi.org/10.1161/CIRCRESAHA.107.151449
Rota M, Hosoda T, De Angelis A, Arcarese ML, Esposito G, Rizzi R et al. The young mouse heart is composed of myocytes heterogeneous in age and function. Circulation Research. 2007 Aug;101(4):387-399. https://doi.org/10.1161/CIRCRESAHA.107.151449
Rota, Marcello ; Hosoda, Toru ; De Angelis, Antonella ; Arcarese, Michael L. ; Esposito, Grazia ; Rizzi, Roberto ; Tillmanns, Jochen ; Tugal, Derin ; Musso, Ezio ; Rimoldi, Ornella ; Bearzi, Claudia ; Urbanek, Konrad ; Anversa, Piero ; Leri, Annarosa ; Kajstura, Jan. / The young mouse heart is composed of myocytes heterogeneous in age and function. In: Circulation Research. 2007 ; Vol. 101, No. 4. pp. 387-399.
@article{ec66db5867be49b9a7be58c4e0184db1,
title = "The young mouse heart is composed of myocytes heterogeneous in age and function",
abstract = "The recognition that the adult heart continuously renews its myocyte compartment raises the possibility that the age and lifespan of myocytes does not coincide with the age and lifespan of the organ and organism. If this were the case, myocyte turnover would result at any age in a myocardium composed by a heterogeneous population of parenchymal cells which are structurally integrated but may contribute differently to myocardial performance. To test this hypothesis, left ventricular myocytes were isolated from mice at 3 months of age and the contractile, electrical, and calcium cycling characteristics of these cells were determined together with the expression of the senescence-associated protein p16 and telomere length. The heart was characterized by the coexistence of young, aged, and senescent myocytes. Old nonreplicating, p16-positive, hypertrophied myocytes with severe telomeric shortening were present together with young, dividing, p16-negative, small myocytes with long telomeres. A class of myocytes with intermediate properties was also found. Physiologically, evidence was obtained in favor of the critical role that action potential (AP) duration and ICaL play in potentiating Ca cycling and the mechanical behavior of young myocytes or in decreasing Ca transients and the performance of senescent hypertrophied cells. The characteristics of the AP appeared to be modulated by the transient outward K current Ito which was influenced by the different expression of the K channels subunits. Collectively, these observations at the physiological and structural cellular level document that by necessity the heart has to constantly repopulate its myocyte compartment to replace senescent poorly contracting myocytes with younger more efficient cells. Thus, cardiac homeostasis and myocyte turnover regulate cardiac function.",
keywords = "Action potential profile, Excitation-contraction coupling, Myocyte volume, Senescence-associated proteins, Telomere length",
author = "Marcello Rota and Toru Hosoda and {De Angelis}, Antonella and Arcarese, {Michael L.} and Grazia Esposito and Roberto Rizzi and Jochen Tillmanns and Derin Tugal and Ezio Musso and Ornella Rimoldi and Claudia Bearzi and Konrad Urbanek and Piero Anversa and Annarosa Leri and Jan Kajstura",
year = "2007",
month = "8",
doi = "10.1161/CIRCRESAHA.107.151449",
language = "English",
volume = "101",
pages = "387--399",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - The young mouse heart is composed of myocytes heterogeneous in age and function

AU - Rota, Marcello

AU - Hosoda, Toru

AU - De Angelis, Antonella

AU - Arcarese, Michael L.

AU - Esposito, Grazia

AU - Rizzi, Roberto

AU - Tillmanns, Jochen

AU - Tugal, Derin

AU - Musso, Ezio

AU - Rimoldi, Ornella

AU - Bearzi, Claudia

AU - Urbanek, Konrad

AU - Anversa, Piero

AU - Leri, Annarosa

AU - Kajstura, Jan

PY - 2007/8

Y1 - 2007/8

N2 - The recognition that the adult heart continuously renews its myocyte compartment raises the possibility that the age and lifespan of myocytes does not coincide with the age and lifespan of the organ and organism. If this were the case, myocyte turnover would result at any age in a myocardium composed by a heterogeneous population of parenchymal cells which are structurally integrated but may contribute differently to myocardial performance. To test this hypothesis, left ventricular myocytes were isolated from mice at 3 months of age and the contractile, electrical, and calcium cycling characteristics of these cells were determined together with the expression of the senescence-associated protein p16 and telomere length. The heart was characterized by the coexistence of young, aged, and senescent myocytes. Old nonreplicating, p16-positive, hypertrophied myocytes with severe telomeric shortening were present together with young, dividing, p16-negative, small myocytes with long telomeres. A class of myocytes with intermediate properties was also found. Physiologically, evidence was obtained in favor of the critical role that action potential (AP) duration and ICaL play in potentiating Ca cycling and the mechanical behavior of young myocytes or in decreasing Ca transients and the performance of senescent hypertrophied cells. The characteristics of the AP appeared to be modulated by the transient outward K current Ito which was influenced by the different expression of the K channels subunits. Collectively, these observations at the physiological and structural cellular level document that by necessity the heart has to constantly repopulate its myocyte compartment to replace senescent poorly contracting myocytes with younger more efficient cells. Thus, cardiac homeostasis and myocyte turnover regulate cardiac function.

AB - The recognition that the adult heart continuously renews its myocyte compartment raises the possibility that the age and lifespan of myocytes does not coincide with the age and lifespan of the organ and organism. If this were the case, myocyte turnover would result at any age in a myocardium composed by a heterogeneous population of parenchymal cells which are structurally integrated but may contribute differently to myocardial performance. To test this hypothesis, left ventricular myocytes were isolated from mice at 3 months of age and the contractile, electrical, and calcium cycling characteristics of these cells were determined together with the expression of the senescence-associated protein p16 and telomere length. The heart was characterized by the coexistence of young, aged, and senescent myocytes. Old nonreplicating, p16-positive, hypertrophied myocytes with severe telomeric shortening were present together with young, dividing, p16-negative, small myocytes with long telomeres. A class of myocytes with intermediate properties was also found. Physiologically, evidence was obtained in favor of the critical role that action potential (AP) duration and ICaL play in potentiating Ca cycling and the mechanical behavior of young myocytes or in decreasing Ca transients and the performance of senescent hypertrophied cells. The characteristics of the AP appeared to be modulated by the transient outward K current Ito which was influenced by the different expression of the K channels subunits. Collectively, these observations at the physiological and structural cellular level document that by necessity the heart has to constantly repopulate its myocyte compartment to replace senescent poorly contracting myocytes with younger more efficient cells. Thus, cardiac homeostasis and myocyte turnover regulate cardiac function.

KW - Action potential profile

KW - Excitation-contraction coupling

KW - Myocyte volume

KW - Senescence-associated proteins

KW - Telomere length

UR - http://www.scopus.com/inward/record.url?scp=34547938711&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547938711&partnerID=8YFLogxK

U2 - 10.1161/CIRCRESAHA.107.151449

DO - 10.1161/CIRCRESAHA.107.151449

M3 - Article

C2 - 17601802

AN - SCOPUS:34547938711

VL - 101

SP - 387

EP - 399

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 4

ER -