Atherogenic endothelial cell eNOS and ET-1 responses to asynchronous hemodynamics are mitigated by conjugated linoleic acid

Michael B. Dancu, Danielle E. Berardi, John Patrick Vanden Heuvel, John M. Tarbell

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Although local wall shear stress (WSS) induced by blood flow has been implicated in atherogenesis, another prominent and often neglected hemodynamic feature, circumferential strain (CS) driven by pressure, is induced concurrently. To investigate endothelial cell (EC) responses to pathologic hemodynamics and their possible manipulation by pharmaceuticals, we simulated complete hemodynamic conditions comprised of simultaneous WSS and CS during treatment with conjugated linoleic acid (CLA), a known PPAR (-α and -γ) activator and anti-atherogenic agent, on cultured EC and examined effects on gene and metabolite expression. Two hemodynamic conditions representative of distinct regions of the circulation, coronary arteries: pro-atherogenic (asynchronous WSS and CS) and straight descending aorta: non-atherogenic (synchronous WSS and CS), were applied to cultured EC during treatment with the nutraceutical CLA. Competitive-quantitative RT-PCR showed that asynchronous hemodynamics significantly reduced (2-fold) eNOS and PPAR-γ mRNA levels compared to synchronous hemodynamics at 5 and 12h. ET-1 showed an opposite trend at 12h. CLA treatment mitigated pro-atherogenic eNOS, ET-1, PPAR-α and -γ mRNA expression profiles and NO and ET-1 secretion patterns during asynchronous hemodynamics. This study demonstrates the potential for a pharmacological treatment (CLA) to normalize pro-atherogenic gene expression profiles induced by hemodynamics inherent to the circulation.

Original languageEnglish (US)
Pages (from-to)1111-1119
Number of pages9
JournalAnnals of Biomedical Engineering
Volume35
Issue number7
DOIs
StatePublished - Jul 1 2007

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Linoleic acid
Endothelial cells
Hemodynamics
Shear stress
Metabolites
Gene expression
Drug products
Blood
Genes

All Science Journal Classification (ASJC) codes

  • Biomedical Engineering

Cite this

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abstract = "Although local wall shear stress (WSS) induced by blood flow has been implicated in atherogenesis, another prominent and often neglected hemodynamic feature, circumferential strain (CS) driven by pressure, is induced concurrently. To investigate endothelial cell (EC) responses to pathologic hemodynamics and their possible manipulation by pharmaceuticals, we simulated complete hemodynamic conditions comprised of simultaneous WSS and CS during treatment with conjugated linoleic acid (CLA), a known PPAR (-α and -γ) activator and anti-atherogenic agent, on cultured EC and examined effects on gene and metabolite expression. Two hemodynamic conditions representative of distinct regions of the circulation, coronary arteries: pro-atherogenic (asynchronous WSS and CS) and straight descending aorta: non-atherogenic (synchronous WSS and CS), were applied to cultured EC during treatment with the nutraceutical CLA. Competitive-quantitative RT-PCR showed that asynchronous hemodynamics significantly reduced (2-fold) eNOS and PPAR-γ mRNA levels compared to synchronous hemodynamics at 5 and 12h. ET-1 showed an opposite trend at 12h. CLA treatment mitigated pro-atherogenic eNOS, ET-1, PPAR-α and -γ mRNA expression profiles and NO and ET-1 secretion patterns during asynchronous hemodynamics. This study demonstrates the potential for a pharmacological treatment (CLA) to normalize pro-atherogenic gene expression profiles induced by hemodynamics inherent to the circulation.",
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Atherogenic endothelial cell eNOS and ET-1 responses to asynchronous hemodynamics are mitigated by conjugated linoleic acid. / Dancu, Michael B.; Berardi, Danielle E.; Vanden Heuvel, John Patrick; Tarbell, John M.

In: Annals of Biomedical Engineering, Vol. 35, No. 7, 01.07.2007, p. 1111-1119.

Research output: Contribution to journalArticle

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