Caloric restriction ameliorates angiotensin II-induced mitochondrial remodeling and cardiac hypertrophy

Piet Finckenberg, Ove Eriksson, Marc Baumann, Saara Merasto, Maciej M. Lalowski, Jouko Levijoki, Kristiina Haasio, Ville Kytö, Dominik N. Muller, Friedrich C. Luft, Matej Orešič, Eero Mervaala (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

37 Citations (Scopus)

Abstract

Angiotensin II-induced cardiac damage is associated with oxidative stress-dependent mitochondrial dysfunction. Caloric restriction (CR), a dietary regimen that increases mitochondrial activity and cellular stress resistance, could provide protection. We tested that hypothesis in double transgenic rats harboring human renin and angiotensinogen genes (dTGRs). CR (60% of energy intake for 4 weeks) decreased mortality in dTGRs. CR ameliorated angiotensin II-induced cardiomyocyte hypertrophy, vascular inflammation, cardiac damage and fibrosis, cardiomyocyte apoptosis, and cardiac atrial natriuretic peptide mRNA overexpression. The effects were blood pressure independent and were linked to increased endoplasmic reticulum stress, autophagy, serum adiponectin level, and 5' AMP-activated protein kinase phosphorylation. CR decreased cardiac p38 phosphorylation, nitrotyrosine expression, and serum insulin-like growth factor 1 levels. Mitochondria from dTGR hearts showed clustered mitochondrial patterns, decreased numbers, and volume fractions but increased trans-sectional areas. All of these effects were reduced in CR dTGRs. Mitochondrial proteomic profiling identified 43 dTGR proteins and 42 Sprague-Dawley proteins, of which 29 proteins were in common in response to CR. We identified 7 proteins in CR dTGRs that were not found in control dTGRs. In contrast, 6 mitochondrial proteins were identified from dTGRs that were not detected in any other group. Gene ontology annotations with the Panther protein classification system revealed downregulation of cytoskeletal proteins and enzyme modulators and upregulation of oxidoreductase activity in dTGRs. CR provides powerful, blood pressure-independent, protection against angiotensin II-induced mitochondrial remodeling and cardiac hypertrophy. The findings support the notion of modulating cardiac bioenergetics to ameliorate angiotensin II-induced cardiovascular complications.
Original languageEnglish
Pages (from-to)76-84
JournalHypertension
Volume59
Issue number1
DOIs
Publication statusPublished - 2012
MoE publication typeA1 Journal article-refereed

Fingerprint

Caloric Restriction
Cardiomegaly
Angiotensin II
Proteins
Cardiac Myocytes
Phosphorylation
Transgenic Rats
Blood Pressure
Molecular Sequence Annotation
Heart Mitochondria
Angiotensinogen
Gene Ontology
AMP-Activated Protein Kinases
Endoplasmic Reticulum Stress
Cytoskeletal Proteins
Mitochondrial Proteins
Adiponectin
Autophagy
Atrial Natriuretic Factor
Somatomedins

Keywords

  • hypertension
  • hypertrophy
  • caloric restriction
  • renin-angiotensin system
  • mitochondria
  • oxidative stress

Cite this

Finckenberg, P., Eriksson, O., Baumann, M., Merasto, S., Lalowski, M. M., Levijoki, J., ... Mervaala, E. (2012). Caloric restriction ameliorates angiotensin II-induced mitochondrial remodeling and cardiac hypertrophy. Hypertension, 59(1), 76-84. https://doi.org/10.1161/HYPERTENSIONAHA.111.179457
Finckenberg, Piet ; Eriksson, Ove ; Baumann, Marc ; Merasto, Saara ; Lalowski, Maciej M. ; Levijoki, Jouko ; Haasio, Kristiina ; Kytö, Ville ; Muller, Dominik N. ; Luft, Friedrich C. ; Orešič, Matej ; Mervaala, Eero. / Caloric restriction ameliorates angiotensin II-induced mitochondrial remodeling and cardiac hypertrophy. In: Hypertension. 2012 ; Vol. 59, No. 1. pp. 76-84.
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Finckenberg, P, Eriksson, O, Baumann, M, Merasto, S, Lalowski, MM, Levijoki, J, Haasio, K, Kytö, V, Muller, DN, Luft, FC, Orešič, M & Mervaala, E 2012, 'Caloric restriction ameliorates angiotensin II-induced mitochondrial remodeling and cardiac hypertrophy', Hypertension, vol. 59, no. 1, pp. 76-84. https://doi.org/10.1161/HYPERTENSIONAHA.111.179457

Caloric restriction ameliorates angiotensin II-induced mitochondrial remodeling and cardiac hypertrophy. / Finckenberg, Piet; Eriksson, Ove; Baumann, Marc; Merasto, Saara; Lalowski, Maciej M.; Levijoki, Jouko; Haasio, Kristiina; Kytö, Ville; Muller, Dominik N.; Luft, Friedrich C.; Orešič, Matej; Mervaala, Eero (Corresponding Author).

In: Hypertension, Vol. 59, No. 1, 2012, p. 76-84.

Research output: Contribution to journalArticleScientificpeer-review

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T1 - Caloric restriction ameliorates angiotensin II-induced mitochondrial remodeling and cardiac hypertrophy

AU - Finckenberg, Piet

AU - Eriksson, Ove

AU - Baumann, Marc

AU - Merasto, Saara

AU - Lalowski, Maciej M.

AU - Levijoki, Jouko

AU - Haasio, Kristiina

AU - Kytö, Ville

AU - Muller, Dominik N.

AU - Luft, Friedrich C.

AU - Orešič, Matej

AU - Mervaala, Eero

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N2 - Angiotensin II-induced cardiac damage is associated with oxidative stress-dependent mitochondrial dysfunction. Caloric restriction (CR), a dietary regimen that increases mitochondrial activity and cellular stress resistance, could provide protection. We tested that hypothesis in double transgenic rats harboring human renin and angiotensinogen genes (dTGRs). CR (60% of energy intake for 4 weeks) decreased mortality in dTGRs. CR ameliorated angiotensin II-induced cardiomyocyte hypertrophy, vascular inflammation, cardiac damage and fibrosis, cardiomyocyte apoptosis, and cardiac atrial natriuretic peptide mRNA overexpression. The effects were blood pressure independent and were linked to increased endoplasmic reticulum stress, autophagy, serum adiponectin level, and 5' AMP-activated protein kinase phosphorylation. CR decreased cardiac p38 phosphorylation, nitrotyrosine expression, and serum insulin-like growth factor 1 levels. Mitochondria from dTGR hearts showed clustered mitochondrial patterns, decreased numbers, and volume fractions but increased trans-sectional areas. All of these effects were reduced in CR dTGRs. Mitochondrial proteomic profiling identified 43 dTGR proteins and 42 Sprague-Dawley proteins, of which 29 proteins were in common in response to CR. We identified 7 proteins in CR dTGRs that were not found in control dTGRs. In contrast, 6 mitochondrial proteins were identified from dTGRs that were not detected in any other group. Gene ontology annotations with the Panther protein classification system revealed downregulation of cytoskeletal proteins and enzyme modulators and upregulation of oxidoreductase activity in dTGRs. CR provides powerful, blood pressure-independent, protection against angiotensin II-induced mitochondrial remodeling and cardiac hypertrophy. The findings support the notion of modulating cardiac bioenergetics to ameliorate angiotensin II-induced cardiovascular complications.

AB - Angiotensin II-induced cardiac damage is associated with oxidative stress-dependent mitochondrial dysfunction. Caloric restriction (CR), a dietary regimen that increases mitochondrial activity and cellular stress resistance, could provide protection. We tested that hypothesis in double transgenic rats harboring human renin and angiotensinogen genes (dTGRs). CR (60% of energy intake for 4 weeks) decreased mortality in dTGRs. CR ameliorated angiotensin II-induced cardiomyocyte hypertrophy, vascular inflammation, cardiac damage and fibrosis, cardiomyocyte apoptosis, and cardiac atrial natriuretic peptide mRNA overexpression. The effects were blood pressure independent and were linked to increased endoplasmic reticulum stress, autophagy, serum adiponectin level, and 5' AMP-activated protein kinase phosphorylation. CR decreased cardiac p38 phosphorylation, nitrotyrosine expression, and serum insulin-like growth factor 1 levels. Mitochondria from dTGR hearts showed clustered mitochondrial patterns, decreased numbers, and volume fractions but increased trans-sectional areas. All of these effects were reduced in CR dTGRs. Mitochondrial proteomic profiling identified 43 dTGR proteins and 42 Sprague-Dawley proteins, of which 29 proteins were in common in response to CR. We identified 7 proteins in CR dTGRs that were not found in control dTGRs. In contrast, 6 mitochondrial proteins were identified from dTGRs that were not detected in any other group. Gene ontology annotations with the Panther protein classification system revealed downregulation of cytoskeletal proteins and enzyme modulators and upregulation of oxidoreductase activity in dTGRs. CR provides powerful, blood pressure-independent, protection against angiotensin II-induced mitochondrial remodeling and cardiac hypertrophy. The findings support the notion of modulating cardiac bioenergetics to ameliorate angiotensin II-induced cardiovascular complications.

KW - hypertension

KW - hypertrophy

KW - caloric restriction

KW - renin-angiotensin system

KW - mitochondria

KW - oxidative stress

U2 - 10.1161/HYPERTENSIONAHA.111.179457

DO - 10.1161/HYPERTENSIONAHA.111.179457

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