Advertisement
Research Article| Volume 192, ISSUE 1, P9-14, May 2007

Coronary endothelium expresses a pathologic gene pattern compared to aortic endothelium: Correlation of asynchronous hemodynamics and pathology in vivo

  • Michael B. Dancu
    Affiliations
    Cardiovascular Dynamics and Biomolecular Transport Laboratory, Department of Biomedical Engineering, The City College of New York/CUNY, New York, NY 10031, United States
    Search for articles by this author
  • John M. Tarbell
    Correspondence
    Corresponding author. Tel.: +1 212 650 6841; fax: +1 212 650 6727.
    Affiliations
    Cardiovascular Dynamics and Biomolecular Transport Laboratory, Department of Biomedical Engineering, The City College of New York/CUNY, New York, NY 10031, United States
    Search for articles by this author

      Abstract

      Coronary arteries are the most disease prone arteries in the circulation and are characterized by unique hemodynamic features, wherein wall shear stress (WSS) induced by blood flow and circumferential strain (CS) driven by pressure are highly out-of-phase temporally (asynchronous hemodynamics). To investigate whether there is a correlation between asynchronous hemodynamics and pathology in vivo, we examined endothelial cell (EC) gene expression and nuclear morphology in two distinct hemodynamic regions of male New Zealand rabbits: coronary arteries (left anterior descending artery cLAD), and aorta (aortic arch inner curvature, outer curvature, and straight descending aorta).
      En face imaging showed strong similarities in EC nuclear length:width ratio and angle of orientation in the cLAD and aorta. Real-time RT-PCR, however, showed that coronary arteries had significantly reduced (>5-fold) eNOS mRNA levels compared to all aortic regions, while ET-1 showed an opposite trend (∼2.5-fold). Coronary arteries with characteristic asynchronous hemodynamics displayed pro-atherogenic eNOS and ET-1 gene expression profiles while the EC nuclei morphology did not differ from non-atherogenic regions in the aorta. This study demonstrates a correlation between asynchronous hemodynamics and pro-atherogenic gene expression patterns in vivo that is induced by hemodynamics inherent to the circulation.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Davies P.F.
        • Polacek D.C.
        • Handen J.S.
        • Helmke B.P.
        • DePaola N.
        A spatial approach to transcriptional profiling: mechanotransduction and the focal origin of atherosclerosis.
        Trends Biotechnol. 1999; 17: 347-351
        • Garcia-Cardena G.
        • Anderson K.R.
        • Mauri L.
        • Gimbrone Jr, M.A.
        Distinct mechanical stimuli differentially regulate the PI3K/Akt survival pathway in endothelial cells.
        Ann NY Acad Sci. 2000; 902: 294-297
        • Gimbrone Jr, M.A.
        • Topper J.N.
        • Nagel T.
        • Anderson K.R.
        • Garcia-Cardena G.
        Endothelial dysfunction, hemodynamic forces, and atherogenesis.
        Ann NY Acad Sci. 2000; 902 ([discussion 239–40]): 230-239
        • Chien S.
        • Li S.
        • Shyy Y.J.
        Effects of mechanical forces on signal transduction and gene expression in endothelial cells.
        Hypertension. 1998; 31: 162-169
        • Corti R.
        • Fuster V.
        • Badimon J.J.
        • Hutter R.
        • Fayad Z.A.
        New understanding of atherosclerosis (clinically and experimentally) with evolving MRI technology in vivo.
        Ann NY Acad Sci. 2001; 947 ([discussion 195–88]): 181-195
        • VanderLaan P.A.
        • Reardon C.A.
        • Getz G.S.
        Site specificity of atherosclerosis: site-selective responses to atherosclerotic modulators.
        Arterioscler Thromb Vasc Biol. 2004; 24: 12-22
        • Berk B.C.
        • Abe J.I.
        • Min W.
        • Surapisitchat J.
        • Yan C.
        Endothelial atheroprotective and anti-inflammatory mechanisms.
        Ann NY Acad Sci. 2001; 947 ([discussion 93–109]): 109-111
        • Aronow W.S.
        Management of peripheral arterial disease.
        Cardiol Rev. 2005; 13: 61-68
        • Qiu Y.
        • Tarbell J.M.
        Numerical simulation of pulsatile flow in a compliant curved tube model of a coronary artery.
        J Biomech Eng. 2000; 122: 77-85
        • Hoffman J.I.
        • Spaan J.A.
        Pressure-flow relations in coronary circulation.
        Physiol Rev. 1990; 70: 331-390
        • Davies P.F.
        • Shi C.
        • Depaola N.
        • Helmke B.P.
        • Polacek D.C.
        Hemodynamics and the focal origin of atherosclerosis: a spatial approach to endothelial structure, gene expression, and function.
        Ann NY Acad Sci. 2001; 947 ([discussion 16–17]): 7-16
        • Chen B.P.
        • Li Y.S.
        • Zhao Y.
        • et al.
        DNA microarray analysis of gene expression in endothelial cells in response to 24-h shear stress.
        Physiol Genomics. 2001; 7: 55-63
        • Garcia-Cardena G.
        • Comander J.
        • Anderson K.R.
        • Blackman B.R.
        • Gimbrone Jr, M.A.
        Biomechanical activation of vascular endothelium as a determinant of its functional phenotype.
        Proc Natl Acad Sci USA. 2001; 98: 4478-4485
        • McCormick S.M.
        • Eskin S.G.
        • McIntire L.V.
        • et al.
        DNA microarray reveals changes in gene expression of shear stressed human umbilical vein endothelial cells.
        Proc Natl Acad Sci USA. 2001; 98: 8955-8960
        • Wasserman S.M.
        • Mehraban F.
        • Komuves L.G.
        • et al.
        Gene expression profile of human endothelial cells exposed to sustained fluid shear stress.
        Physiol Genomics. 2002; 12: 13-23
        • Qiu Y.
        • Tarbell J.M.
        Numerical simulation of oxygen mass transfer in a compliant curved tube model of a coronary artery.
        Ann Biomed Eng. 2000; 28: 26-38
        • Tada S.
        • Tarbell J.M.
        A computational study of flow in a compliant carotid bifurcation-stress phase angle correlation with shear stress.
        Ann Biomed Eng. 2005; 33: 1202-1212
        • Joshi A.K.
        • Leask R.L.
        • Myers J.G.
        • et al.
        Intimal thickness is not associated with wall shear stress patterns in the human right coronary artery.
        Arterioscler Thromb Vasc Biol. 2004; 24: 2408-2413
        • Mombouli J.V.
        • Vanhoutte P.M.
        Endothelial dysfunction: from physiology to therapy.
        J Mol Cell Cardiol. 1999; 31: 61-74
        • Passerini A.G.
        • Polacek D.C.
        • Shi C.
        • et al.
        Coexisting proinflammatory and antioxidative endothelial transcription profiles in a disturbed flow region of the adult porcine aorta.
        Proc Natl Acad Sci USA. 2004; 101: 2482-2487
        • Tada S.
        • Tarbell J.M.
        Computational study of flow in a complaint carotid bifurcation—stress phase angle correlation with shear stress.
        Ann Biomed Eng. 2005; 33: 1202-1212
        • Qiu Y.
        • Tarbell J.M.
        Interaction between wall shear stress and circumferential strain affects endothelial cell biochemical production.
        J Vasc Res. 2000; 37: 147-157
        • Dancu M.B.
        • Berardi D.E.
        • Vanden Heuvel J.P.
        • Tarbell J.M.
        Asynchronous shear stress and circumferential strain reduces endothelial no synthase and cyclooxygenase-2 but induces endothelin-1 gene expression in endothelial cells.
        Arterioscler Thromb Vasc Biol. 2004; 24: 2088-2099
        • Al-Musawi S.L.
        • Bishton J.
        • Dean J.
        • et al.
        Evidence for a reversal with age in the pattern of near-wall blood flow around aortic branches.
        Atherosclerosis. 2004; 172: 79-84
        • Okano M.
        • Yoshida Y.
        Endothelial cell morphometry of atherosclerotic lesions and flow profiles at aortic bifurcations in cholesterol fed rabbits.
        J Biomech Eng. 1992; 114: 301-308
        • Levesque M.J.
        • Nerem R.M.
        The elongation and orientation of cultured endothelial cells in response to shear stress.
        J Biomech Eng. 1985; 107: 341-347
        • Vanden Heuvel J.P.
        Peroxisome proliferator-activated receptors (PPARS) and carcinogenesis.
        Toxicol Sci. 1999; 47: 1-8
        • Vanden Heuvel J.P.
        • Tyson F.L.
        • Bell D.A.
        Construction of recombinant RNA templates for use as internal standards in quantitative RT-PCR.
        Biotechniques. 1993; 14: 395-398
        • Awolesi M.A.
        • Sessa W.C.
        • Sumpio B.E.
        Cyclic strain upregulates nitric oxide synthase in cultured bovine aortic endothelial cells.
        J Clin Invest. 1995; 96: 1449-1454
        • Carosi J.A.
        • Eskin S.G.
        • McIntire L.V.
        Cyclical strain effects on production of vasoactive materials in cultured endothelial cells.
        J Cell Physiol. 1992; 151: 29-36
        • Kritchevsky D.
        • Tepper S.A.
        • Wright S.
        • Tso P.
        • Czarnecki S.K.
        Influence of conjugated linoleic acid (CLA) on establishment and progression of atherosclerosis in rabbits.
        J Am Coll Nutr. 2000; 19: 472S-477S