Skeletal actin mRNA increases in the human heart during ontogenic development and is the major isoform of control and failing adult hearts

Kenneth R. Boheler, Lucie Carrier, Diane De La Bastie, Paul D. Allen, Michel Komajda, Jean Jacques Mercadier, Ketty Schwartz

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Expression of the two sarcomeric actins, α-skeletal and α-cardiac, is regulated in the rodent heart in response to developmental, hormonal, and hemodynamic stimuli. Little is known in man, except that both isogenes were found to be coexpressed in three adult ventricles. In this report, we investigated the isoactin mRNA composition in ventricles from 21 control patients (4 fetal, 5 juvenile, 12 adult) and from 15 patients undergoing cardiac transplantation (5 idiopathic dilated cardiomyopathies, 5 ischemic myopathies with myocardial infarcts, 5 diverse etiologies) by two different and complementary techniques: RNA dot blot analysis with specific cDNA probes, and primer extensions with an oligonucleotide common to α-cardiac and α-skeletal actins. In the case of dot blot analysis, quantification of each isoform was performed by using as standards RNA transcripts obtained from cloned human α-actin sequences, and the total amount of sarcomeric actin mRNA was evaluated as a function of total poly (A+) RNA. We found that both isogenes are always coexpressed, and that the isoactin pattern changes during development. In utero and in neonatal hearts, α-skeletal actin mRNA represents ≤ 20% of sarcomeric actins, it increases to 48±6% during the first decade after birth and becomes the predominant isoform of adult hearts (60.4±8.5%). The 15 adult failing hearts exhibited the same isoactin pattern as the control ones (62.84±11.06%), and there was no difference in expression between patients with dilated cardiomyopathy or ischemic heart disease. These observations demonstrate that cardiac development in man, in contrast to rodent heart, is characterized by an up-regulation of the skeletal actin gene, the expression of which does not change in hypertrophied and failing hearts, and suggest that the actin and myosin heavy chain families are independently regulated in human heart. (J. Clin. Invest. 1991. 88:323-330.).

Original languageEnglish (US)
Pages (from-to)323-330
Number of pages8
JournalJournal of Clinical Investigation
Volume88
Issue number1
StatePublished - 1991
Externally publishedYes

Fingerprint

Actins
Protein Isoforms
Messenger RNA
Dilated Cardiomyopathy
Rodentia
Complementary RNA
Myosin Heavy Chains
Muscular Diseases
Heart Transplantation
Oligonucleotides
Myocardial Ischemia
Up-Regulation
Complementary DNA
Hemodynamics
Myocardial Infarction
Parturition
RNA
Gene Expression

Keywords

  • Adult human hearts
  • Cardiac actin mRNAs
  • Dot blot analysis, fetal
  • End-stage heart failure
  • Neonatal
  • Primer extension assay
  • Skeletal

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Boheler, K. R., Carrier, L., De La Bastie, D., Allen, P. D., Komajda, M., Mercadier, J. J., & Schwartz, K. (1991). Skeletal actin mRNA increases in the human heart during ontogenic development and is the major isoform of control and failing adult hearts. Journal of Clinical Investigation, 88(1), 323-330.

Skeletal actin mRNA increases in the human heart during ontogenic development and is the major isoform of control and failing adult hearts. / Boheler, Kenneth R.; Carrier, Lucie; De La Bastie, Diane; Allen, Paul D.; Komajda, Michel; Mercadier, Jean Jacques; Schwartz, Ketty.

In: Journal of Clinical Investigation, Vol. 88, No. 1, 1991, p. 323-330.

Research output: Contribution to journalArticle

Boheler, KR, Carrier, L, De La Bastie, D, Allen, PD, Komajda, M, Mercadier, JJ & Schwartz, K 1991, 'Skeletal actin mRNA increases in the human heart during ontogenic development and is the major isoform of control and failing adult hearts', Journal of Clinical Investigation, vol. 88, no. 1, pp. 323-330.
Boheler, Kenneth R. ; Carrier, Lucie ; De La Bastie, Diane ; Allen, Paul D. ; Komajda, Michel ; Mercadier, Jean Jacques ; Schwartz, Ketty. / Skeletal actin mRNA increases in the human heart during ontogenic development and is the major isoform of control and failing adult hearts. In: Journal of Clinical Investigation. 1991 ; Vol. 88, No. 1. pp. 323-330.
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abstract = "Expression of the two sarcomeric actins, α-skeletal and α-cardiac, is regulated in the rodent heart in response to developmental, hormonal, and hemodynamic stimuli. Little is known in man, except that both isogenes were found to be coexpressed in three adult ventricles. In this report, we investigated the isoactin mRNA composition in ventricles from 21 control patients (4 fetal, 5 juvenile, 12 adult) and from 15 patients undergoing cardiac transplantation (5 idiopathic dilated cardiomyopathies, 5 ischemic myopathies with myocardial infarcts, 5 diverse etiologies) by two different and complementary techniques: RNA dot blot analysis with specific cDNA probes, and primer extensions with an oligonucleotide common to α-cardiac and α-skeletal actins. In the case of dot blot analysis, quantification of each isoform was performed by using as standards RNA transcripts obtained from cloned human α-actin sequences, and the total amount of sarcomeric actin mRNA was evaluated as a function of total poly (A+) RNA. We found that both isogenes are always coexpressed, and that the isoactin pattern changes during development. In utero and in neonatal hearts, α-skeletal actin mRNA represents ≤ 20{\%} of sarcomeric actins, it increases to 48±6{\%} during the first decade after birth and becomes the predominant isoform of adult hearts (60.4±8.5{\%}). The 15 adult failing hearts exhibited the same isoactin pattern as the control ones (62.84±11.06{\%}), and there was no difference in expression between patients with dilated cardiomyopathy or ischemic heart disease. These observations demonstrate that cardiac development in man, in contrast to rodent heart, is characterized by an up-regulation of the skeletal actin gene, the expression of which does not change in hypertrophied and failing hearts, and suggest that the actin and myosin heavy chain families are independently regulated in human heart. (J. Clin. Invest. 1991. 88:323-330.).",
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