TY - JOUR
T1 - Atherogenic endothelial cell eNOS and ET-1 responses to asynchronous hemodynamics are mitigated by conjugated linoleic acid
AU - Dancu, Michael B.
AU - Berardi, Danielle E.
AU - Vanden Heuvel, John P.
AU - Tarbell, John M.
N1 - Funding Information:
This study was supported by National Heart Lung and Blood Institute Grant RO1-HL35549. We thank the Center for Carcinogenesis and Molecular Toxicology at Penn State University.
PY - 2007/7
Y1 - 2007/7
N2 - 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.
AB - 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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U2 - 10.1007/s10439-007-9290-1
DO - 10.1007/s10439-007-9290-1
M3 - Article
C2 - 17394083
AN - SCOPUS:34250759396
SN - 0090-6964
VL - 35
SP - 1111
EP - 1119
JO - Annals of Biomedical Engineering
JF - Annals of Biomedical Engineering
IS - 7
ER -