NO and PGI2 in coronary endothelial dysfunction in transgenic mice with dilated cardiomyopathy

Lukasz Drelicharz, Valery Kozlovski, Tomasz Skorka, Sylwia Heinze-Paluchowska, Andrzej Jasinski, Anna Gebska, Tomasz Guzik, Rafal Olszanecki, Leszek Wojnar, Ulrike Mende, Gabor Csanyi, Stefan Chlopicki

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Objective: The aim of the present work was to analyze coronary endothelial function in the transgenic mouse model of dilated cardiomyopathy (Tgαq*44 mice). Methods: Coronary vasodilatation, both NO-dependent (induced by bradykinin) and PGI2-dependent (induced by acetylcholine), was assessed in the isolated hearts of Tgαq*44 and FVB mice. Cardiac function was analyzed in vivo (MRI). Results: In Tgαq*44 mice at the age of 2-4 months cardiac function was preserved and there were no alterations in endothelial function. By contrast, in Tgαq*44 mice at the age of 14-16 months cardiac function was significantly impaired and NO, but not PGI2-dependent coronary function was altered. Interestingly, the basal level of PGI2 in coronary circulation increased fourfold as compared to FVB mice. Cardiac O2- production increased 1.5-fold and 3-fold in Tgαq*44 vs. FVB mice at the age of 2-6 and 14-16 months, respectively, and was inhibited by apocynin. Interestingly, inhibition of NADPH oxidase or NOS-3 normalized augmented PGI2 production in Tgαq*44 mice. There was also an increased expression of gp91phox in Tgαq*44 vs. FVB hearts, without evident alterations in the expression of COX-1, COX-2, NOS-3 and PGI2-synthase. Conclusions: In the mouse model of dilated cardiomyopathy, endothelial dysfunction in coronary circulation is present in the late but not the early stage of heart failure pathology and is characterized by a decrease in NO bioavailability and a compensatory increase in PGI2. Both the decrease in NO activity and the increase in PGI2 activity may result from excessive O2- production by cardiac NADPH oxidase in Tgαq*44 hearts.

Original languageEnglish (US)
Pages (from-to)417-430
Number of pages14
JournalBasic Research in Cardiology
Volume103
Issue number5
DOIs
StatePublished - Apr 23 2008

Fingerprint

Dilated Cardiomyopathy
Epoprostenol
Transgenic Mice
Coronary Circulation
NADPH Oxidase
Bradykinin
Vasodilation
Biological Availability
Acetylcholine
Heart Failure
Pathology

Keywords

  • Dilated cardiomyopathy
  • Endothelial dysfunction
  • Heart failure
  • Nitric oxide
  • Prostacyclin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Drelicharz, L., Kozlovski, V., Skorka, T., Heinze-Paluchowska, S., Jasinski, A., Gebska, A., ... Chlopicki, S. (2008). NO and PGI2 in coronary endothelial dysfunction in transgenic mice with dilated cardiomyopathy. Basic Research in Cardiology, 103(5), 417-430. https://doi.org/10.1007/s00395-008-0723-2

NO and PGI2 in coronary endothelial dysfunction in transgenic mice with dilated cardiomyopathy. / Drelicharz, Lukasz; Kozlovski, Valery; Skorka, Tomasz; Heinze-Paluchowska, Sylwia; Jasinski, Andrzej; Gebska, Anna; Guzik, Tomasz; Olszanecki, Rafal; Wojnar, Leszek; Mende, Ulrike; Csanyi, Gabor; Chlopicki, Stefan.

In: Basic Research in Cardiology, Vol. 103, No. 5, 23.04.2008, p. 417-430.

Research output: Contribution to journalArticle

Drelicharz, L, Kozlovski, V, Skorka, T, Heinze-Paluchowska, S, Jasinski, A, Gebska, A, Guzik, T, Olszanecki, R, Wojnar, L, Mende, U, Csanyi, G & Chlopicki, S 2008, 'NO and PGI2 in coronary endothelial dysfunction in transgenic mice with dilated cardiomyopathy', Basic Research in Cardiology, vol. 103, no. 5, pp. 417-430. https://doi.org/10.1007/s00395-008-0723-2
Drelicharz L, Kozlovski V, Skorka T, Heinze-Paluchowska S, Jasinski A, Gebska A et al. NO and PGI2 in coronary endothelial dysfunction in transgenic mice with dilated cardiomyopathy. Basic Research in Cardiology. 2008 Apr 23;103(5):417-430. https://doi.org/10.1007/s00395-008-0723-2
Drelicharz, Lukasz ; Kozlovski, Valery ; Skorka, Tomasz ; Heinze-Paluchowska, Sylwia ; Jasinski, Andrzej ; Gebska, Anna ; Guzik, Tomasz ; Olszanecki, Rafal ; Wojnar, Leszek ; Mende, Ulrike ; Csanyi, Gabor ; Chlopicki, Stefan. / NO and PGI2 in coronary endothelial dysfunction in transgenic mice with dilated cardiomyopathy. In: Basic Research in Cardiology. 2008 ; Vol. 103, No. 5. pp. 417-430.
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AU - Kozlovski, Valery

AU - Skorka, Tomasz

AU - Heinze-Paluchowska, Sylwia

AU - Jasinski, Andrzej

AU - Gebska, Anna

AU - Guzik, Tomasz

AU - Olszanecki, Rafal

AU - Wojnar, Leszek

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KW - Dilated cardiomyopathy

KW - Endothelial dysfunction

KW - Heart failure

KW - Nitric oxide

KW - Prostacyclin

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