Segmental aortic stiffening contributes to experimental abdominal aortic aneurysm development.

Autor:	Raaz U; From Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (U.R., I.N.S., R.T., F.N., Y.K., M.A., A.D., A.J., J.MS., P.S.T.); Cardiovascular Institute, Stanford University School of Medicine, CA (U.R., A.M.Z., F.N., M.B., F.C.E., Y.K., M.A., R.L.D., J.M.S., P.S.T.); VA Palo Alto Health Care System, CA (U.R., I.N.S., Y.K., M.A., A.D., A.J., J.M.S., P.S.T.); Department of Mechanical Engineering, Stanford University School of Medicine, CA (A.M.Z., E.K.); Department of Cardiothoracic Surgery, Stanford University School of Medicine, CA (F.C.E., E.K.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (S.E., L.M.); Center for Vascular Medicine, Zwickau, Germany (T.H.); Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.); Division of Vascular Surgery, Stanford University School of Medicine, CA (R.L.D.); and Department of Bioengineering, Stanford University School of Medicine, CA (E.K.)., Zöllner AM; From Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (U.R., I.N.S., R.T., F.N., Y.K., M.A., A.D., A.J., J.MS., P.S.T.); Cardiovascular Institute, Stanford University School of Medicine, CA (U.R., A.M.Z., F.N., M.B., F.C.E., Y.K., M.A., R.L.D., J.M.S., P.S.T.); VA Palo Alto Health Care System, CA (U.R., I.N.S., Y.K., M.A., A.D., A.J., J.M.S., P.S.T.); Department of Mechanical Engineering, Stanford University School of Medicine, CA (A.M.Z., E.K.); Department of Cardiothoracic Surgery, Stanford University School of Medicine, CA (F.C.E., E.K.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (S.E., L.M.); Center for Vascular Medicine, Zwickau, Germany (T.H.); Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.); Division of Vascular Surgery, Stanford University School of Medicine, CA (R.L.D.); and Department of Bioengineering, Stanford University School of Medicine, CA (E.K.)., Schellinger IN; From Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (U.R., I.N.S., R.T., F.N., Y.K., M.A., A.D., A.J., J.MS., P.S.T.); Cardiovascular Institute, Stanford University School of Medicine, CA (U.R., A.M.Z., F.N., M.B., F.C.E., Y.K., M.A., R.L.D., J.M.S., P.S.T.); VA Palo Alto Health Care System, CA (U.R., I.N.S., Y.K., M.A., A.D., A.J., J.M.S., P.S.T.); Department of Mechanical Engineering, Stanford University School of Medicine, CA (A.M.Z., E.K.); Department of Cardiothoracic Surgery, Stanford University School of Medicine, CA (F.C.E., E.K.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (S.E., L.M.); Center for Vascular Medicine, Zwickau, Germany (T.H.); Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.); Division of Vascular Surgery, Stanford University School of Medicine, CA (R.L.D.); and Department of Bioengineering, Stanford University School of Medicine, CA (E.K.)., Toh R; From Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (U.R., I.N.S., R.T., F.N., Y.K., M.A., A.D., A.J., J.MS., P.S.T.); Cardiovascular Institute, Stanford University School of Medicine, CA (U.R., A.M.Z., F.N., M.B., F.C.E., Y.K., M.A., R.L.D., J.M.S., P.S.T.); VA Palo Alto Health Care System, CA (U.R., I.N.S., Y.K., M.A., A.D., A.J., J.M.S., P.S.T.); Department of Mechanical Engineering, Stanford University School of Medicine, CA (A.M.Z., E.K.); Department of Cardiothoracic Surgery, Stanford University School of Medicine, CA (F.C.E., E.K.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (S.E., L.M.); Center for Vascular Medicine, Zwickau, Germany (T.H.); Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.); Division of Vascular Surgery, Stanford University School of Medicine, CA (R.L.D.); and Department of Bioengineering, Stanford University School of Medicine, CA (E.K.)., Nakagami F; From Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (U.R., I.N.S., R.T., F.N., Y.K., M.A., A.D., A.J., J.MS., P.S.T.); Cardiovascular Institute, Stanford University School of Medicine, CA (U.R., A.M.Z., F.N., M.B., F.C.E., Y.K., M.A., R.L.D., J.M.S., P.S.T.); VA Palo Alto Health Care System, CA (U.R., I.N.S., Y.K., M.A., A.D., A.J., J.M.S., P.S.T.); Department of Mechanical Engineering, Stanford University School of Medicine, CA (A.M.Z., E.K.); Department of Cardiothoracic Surgery, Stanford University School of Medicine, CA (F.C.E., E.K.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (S.E., L.M.); Center for Vascular Medicine, Zwickau, Germany (T.H.); Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.); Division of Vascular Surgery, Stanford University School of Medicine, CA (R.L.D.); and Department of Bioengineering, Stanford University School of Medicine, CA (E.K.)., Brandt M; From Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (U.R., I.N.S., R.T., F.N., Y.K., M.A., A.D., A.J., J.MS., P.S.T.); Cardiovascular Institute, Stanford University School of Medicine, CA (U.R., A.M.Z., F.N., M.B., F.C.E., Y.K., M.A., R.L.D., J.M.S., P.S.T.); VA Palo Alto Health Care System, CA (U.R., I.N.S., Y.K., M.A., A.D., A.J., J.M.S., P.S.T.); Department of Mechanical Engineering, Stanford University School of Medicine, CA (A.M.Z., E.K.); Department of Cardiothoracic Surgery, Stanford University School of Medicine, CA (F.C.E., E.K.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (S.E., L.M.); Center for Vascular Medicine, Zwickau, Germany (T.H.); Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.); Division of Vascular Surgery, Stanford University School of Medicine, CA (R.L.D.); and Department of Bioengineering, Stanford University School of Medicine, CA (E.K.)., Emrich FC; From Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (U.R., I.N.S., R.T., F.N., Y.K., M.A., A.D., A.J., J.MS., P.S.T.); Cardiovascular Institute, Stanford University School of Medicine, CA (U.R., A.M.Z., F.N., M.B., F.C.E., Y.K., M.A., R.L.D., J.M.S., P.S.T.); VA Palo Alto Health Care System, CA (U.R., I.N.S., Y.K., M.A., A.D., A.J., J.M.S., P.S.T.); Department of Mechanical Engineering, Stanford University School of Medicine, CA (A.M.Z., E.K.); Department of Cardiothoracic Surgery, Stanford University School of Medicine, CA (F.C.E., E.K.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (S.E., L.M.); Center for Vascular Medicine, Zwickau, Germany (T.H.); Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.); Division of Vascular Surgery, Stanford University School of Medicine, CA (R.L.D.); and Department of Bioengineering, Stanford University School of Medicine, CA (E.K.)., Kayama Y; From Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (U.R., I.N.S., R.T., F.N., Y.K., M.A., A.D., A.J., J.MS., P.S.T.); Cardiovascular Institute, Stanford University School of Medicine, CA (U.R., A.M.Z., F.N., M.B., F.C.E., Y.K., M.A., R.L.D., J.M.S., P.S.T.); VA Palo Alto Health Care System, CA (U.R., I.N.S., Y.K., M.A., A.D., A.J., J.M.S., P.S.T.); Department of Mechanical Engineering, Stanford University School of Medicine, CA (A.M.Z., E.K.); Department of Cardiothoracic Surgery, Stanford University School of Medicine, CA (F.C.E., E.K.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (S.E., L.M.); Center for Vascular Medicine, Zwickau, Germany (T.H.); Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.); Division of Vascular Surgery, Stanford University School of Medicine, CA (R.L.D.); and Department of Bioengineering, Stanford University School of Medicine, CA (E.K.)., Eken S; From Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (U.R., I.N.S., R.T., F.N., Y.K., M.A., A.D., A.J., J.MS., P.S.T.); Cardiovascular Institute, Stanford University School of Medicine, CA (U.R., A.M.Z., F.N., M.B., F.C.E., Y.K., M.A., R.L.D., J.M.S., P.S.T.); VA Palo Alto Health Care System, CA (U.R., I.N.S., Y.K., M.A., A.D., A.J., J.M.S., P.S.T.); Department of Mechanical Engineering, Stanford University School of Medicine, CA (A.M.Z., E.K.); Department of Cardiothoracic Surgery, Stanford University School of Medicine, CA (F.C.E., E.K.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (S.E., L.M.); Center for Vascular Medicine, Zwickau, Germany (T.H.); Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.); Division of Vascular Surgery, Stanford University School of Medicine, CA (R.L.D.); and Department of Bioengineering, Stanford University School of Medicine, CA (E.K.)., Adam M; From Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (U.R., I.N.S., R.T., F.N., Y.K., M.A., A.D., A.J., J.MS., P.S.T.); Cardiovascular Institute, Stanford University School of Medicine, CA (U.R., A.M.Z., F.N., M.B., F.C.E., Y.K., M.A., R.L.D., J.M.S., P.S.T.); VA Palo Alto Health Care System, CA (U.R., I.N.S., Y.K., M.A., A.D., A.J., J.M.S., P.S.T.); Department of Mechanical Engineering, Stanford University School of Medicine, CA (A.M.Z., E.K.); Department of Cardiothoracic Surgery, Stanford University School of Medicine, CA (F.C.E., E.K.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (S.E., L.M.); Center for Vascular Medicine, Zwickau, Germany (T.H.); Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.); Division of Vascular Surgery, Stanford University School of Medicine, CA (R.L.D.); and Department of Bioengineering, Stanford University School of Medicine, CA (E.K.)., Maegdefessel L; From Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (U.R., I.N.S., R.T., F.N., Y.K., M.A., A.D., A.J., J.MS., P.S.T.); Cardiovascular Institute, Stanford University School of Medicine, CA (U.R., A.M.Z., F.N., M.B., F.C.E., Y.K., M.A., R.L.D., J.M.S., P.S.T.); VA Palo Alto Health Care System, CA (U.R., I.N.S., Y.K., M.A., A.D., A.J., J.M.S., P.S.T.); Department of Mechanical Engineering, Stanford University School of Medicine, CA (A.M.Z., E.K.); Department of Cardiothoracic Surgery, Stanford University School of Medicine, CA (F.C.E., E.K.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (S.E., L.M.); Center for Vascular Medicine, Zwickau, Germany (T.H.); Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.); Division of Vascular Surgery, Stanford University School of Medicine, CA (R.L.D.); and Department of Bioengineering, Stanford University School of Medicine, CA (E.K.)., Hertel T; From Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (U.R., I.N.S., R.T., F.N., Y.K., M.A., A.D., A.J., J.MS., P.S.T.); Cardiovascular Institute, Stanford University School of Medicine, CA (U.R., A.M.Z., F.N., M.B., F.C.E., Y.K., M.A., R.L.D., J.M.S., P.S.T.); VA Palo Alto Health Care System, CA (U.R., I.N.S., Y.K., M.A., A.D., A.J., J.M.S., P.S.T.); Department of Mechanical Engineering, Stanford University School of Medicine, CA (A.M.Z., E.K.); Department of Cardiothoracic Surgery, Stanford University School of Medicine, CA (F.C.E., E.K.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (S.E., L.M.); Center for Vascular Medicine, Zwickau, Germany (T.H.); Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.); Division of Vascular Surgery, Stanford University School of Medicine, CA (R.L.D.); and Department of Bioengineering, Stanford University School of Medicine, CA (E.K.)., Deng A; From Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (U.R., I.N.S., R.T., F.N., Y.K., M.A., A.D., A.J., J.MS., P.S.T.); Cardiovascular Institute, Stanford University School of Medicine, CA (U.R., A.M.Z., F.N., M.B., F.C.E., Y.K., M.A., R.L.D., J.M.S., P.S.T.); VA Palo Alto Health Care System, CA (U.R., I.N.S., Y.K., M.A., A.D., A.J., J.M.S., P.S.T.); Department of Mechanical Engineering, Stanford University School of Medicine, CA (A.M.Z., E.K.); Department of Cardiothoracic Surgery, Stanford University School of Medicine, CA (F.C.E., E.K.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (S.E., L.M.); Center for Vascular Medicine, Zwickau, Germany (T.H.); Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.); Division of Vascular Surgery, Stanford University School of Medicine, CA (R.L.D.); and Department of Bioengineering, Stanford University School of Medicine, CA (E.K.)., Jagger A; From Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (U.R., I.N.S., R.T., F.N., Y.K., M.A., A.D., A.J., J.MS., P.S.T.); Cardiovascular Institute, Stanford University School of Medicine, CA (U.R., A.M.Z., F.N., M.B., F.C.E., Y.K., M.A., R.L.D., J.M.S., P.S.T.); VA Palo Alto Health Care System, CA (U.R., I.N.S., Y.K., M.A., A.D., A.J., J.M.S., P.S.T.); Department of Mechanical Engineering, Stanford University School of Medicine, CA (A.M.Z., E.K.); Department of Cardiothoracic Surgery, Stanford University School of Medicine, CA (F.C.E., E.K.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (S.E., L.M.); Center for Vascular Medicine, Zwickau, Germany (T.H.); Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.); Division of Vascular Surgery, Stanford University School of Medicine, CA (R.L.D.); and Department of Bioengineering, Stanford University School of Medicine, CA (E.K.)., Buerke M; From Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (U.R., I.N.S., R.T., F.N., Y.K., M.A., A.D., A.J., J.MS., P.S.T.); Cardiovascular Institute, Stanford University School of Medicine, CA (U.R., A.M.Z., F.N., M.B., F.C.E., Y.K., M.A., R.L.D., J.M.S., P.S.T.); VA Palo Alto Health Care System, CA (U.R., I.N.S., Y.K., M.A., A.D., A.J., J.M.S., P.S.T.); Department of Mechanical Engineering, Stanford University School of Medicine, CA (A.M.Z., E.K.); Department of Cardiothoracic Surgery, Stanford University School of Medicine, CA (F.C.E., E.K.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (S.E., L.M.); Center for Vascular Medicine, Zwickau, Germany (T.H.); Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.); Division of Vascular Surgery, Stanford University School of Medicine, CA (R.L.D.); and Department of Bioengineering, Stanford University School of Medicine, CA (E.K.)., Dalman RL; From Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (U.R., I.N.S., R.T., F.N., Y.K., M.A., A.D., A.J., J.MS., P.S.T.); Cardiovascular Institute, Stanford University School of Medicine, CA (U.R., A.M.Z., F.N., M.B., F.C.E., Y.K., M.A., R.L.D., J.M.S., P.S.T.); VA Palo Alto Health Care System, CA (U.R., I.N.S., Y.K., M.A., A.D., A.J., J.M.S., P.S.T.); Department of Mechanical Engineering, Stanford University School of Medicine, CA (A.M.Z., E.K.); Department of Cardiothoracic Surgery, Stanford University School of Medicine, CA (F.C.E., E.K.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (S.E., L.M.); Center for Vascular Medicine, Zwickau, Germany (T.H.); Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.); Division of Vascular Surgery, Stanford University School of Medicine, CA (R.L.D.); and Department of Bioengineering, Stanford University School of Medicine, CA (E.K.)., Spin JM; From Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (U.R., I.N.S., R.T., F.N., Y.K., M.A., A.D., A.J., J.MS., P.S.T.); Cardiovascular Institute, Stanford University School of Medicine, CA (U.R., A.M.Z., F.N., M.B., F.C.E., Y.K., M.A., R.L.D., J.M.S., P.S.T.); VA Palo Alto Health Care System, CA (U.R., I.N.S., Y.K., M.A., A.D., A.J., J.M.S., P.S.T.); Department of Mechanical Engineering, Stanford University School of Medicine, CA (A.M.Z., E.K.); Department of Cardiothoracic Surgery, Stanford University School of Medicine, CA (F.C.E., E.K.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (S.E., L.M.); Center for Vascular Medicine, Zwickau, Germany (T.H.); Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.); Division of Vascular Surgery, Stanford University School of Medicine, CA (R.L.D.); and Department of Bioengineering, Stanford University School of Medicine, CA (E.K.)., Kuhl E; From Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (U.R., I.N.S., R.T., F.N., Y.K., M.A., A.D., A.J., J.MS., P.S.T.); Cardiovascular Institute, Stanford University School of Medicine, CA (U.R., A.M.Z., F.N., M.B., F.C.E., Y.K., M.A., R.L.D., J.M.S., P.S.T.); VA Palo Alto Health Care System, CA (U.R., I.N.S., Y.K., M.A., A.D., A.J., J.M.S., P.S.T.); Department of Mechanical Engineering, Stanford University School of Medicine, CA (A.M.Z., E.K.); Department of Cardiothoracic Surgery, Stanford University School of Medicine, CA (F.C.E., E.K.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (S.E., L.M.); Center for Vascular Medicine, Zwickau, Germany (T.H.); Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.); Division of Vascular Surgery, Stanford University School of Medicine, CA (R.L.D.); and Department of Bioengineering, Stanford University School of Medicine, CA (E.K.)., Tsao PS; From Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (U.R., I.N.S., R.T., F.N., Y.K., M.A., A.D., A.J., J.MS., P.S.T.); Cardiovascular Institute, Stanford University School of Medicine, CA (U.R., A.M.Z., F.N., M.B., F.C.E., Y.K., M.A., R.L.D., J.M.S., P.S.T.); VA Palo Alto Health Care System, CA (U.R., I.N.S., Y.K., M.A., A.D., A.J., J.M.S., P.S.T.); Department of Mechanical Engineering, Stanford University School of Medicine, CA (A.M.Z., E.K.); Department of Cardiothoracic Surgery, Stanford University School of Medicine, CA (F.C.E., E.K.); Department of Medicine, Karolinska Institute, Stockholm, Sweden (S.E., L.M.); Center for Vascular Medicine, Zwickau, Germany (T.H.); Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.); Division of Vascular Surgery, Stanford University School of Medicine, CA (R.L.D.); and Department of Bioengineering, Stanford University School of Medicine, CA (E.K.). ptsao@stanford.edu.
Jazyk:	angličtina
Zdroj:	Circulation [Circulation] 2015 May 19; Vol. 131 (20), pp. 1783-95. Date of Electronic Publication: 2015 Apr 22.
DOI:	10.1161/CIRCULATIONAHA.114.012377
Abstrakt:	Background: Stiffening of the aortic wall is a phenomenon consistently observed in age and in abdominal aortic aneurysm (AAA). However, its role in AAA pathophysiology is largely undefined. Methods and Results: Using an established murine elastase-induced AAA model, we demonstrate that segmental aortic stiffening precedes aneurysm growth. Finite-element analysis reveals that early stiffening of the aneurysm-prone aortic segment leads to axial (longitudinal) wall stress generated by cyclic (systolic) tethering of adjacent, more compliant wall segments. Interventional stiffening of AAA-adjacent aortic segments (via external application of surgical adhesive) significantly reduces aneurysm growth. These changes correlate with the reduced segmental stiffness of the AAA-prone aorta (attributable to equalized stiffness in adjacent segments), reduced axial wall stress, decreased production of reactive oxygen species, attenuated elastin breakdown, and decreased expression of inflammatory cytokines and macrophage infiltration, and attenuated apoptosis within the aortic wall, as well. Cyclic pressurization of segmentally stiffened aortic segments ex vivo increases the expression of genes related to inflammation and extracellular matrix remodeling. Finally, human ultrasound studies reveal that aging, a significant AAA risk factor, is accompanied by segmental infrarenal aortic stiffening. Conclusions: The present study introduces the novel concept of segmental aortic stiffening as an early pathomechanism generating aortic wall stress and triggering aneurysmal growth, thereby delineating potential underlying molecular mechanisms and therapeutic targets. In addition, monitoring segmental aortic stiffening may aid the identification of patients at risk for AAA. (© 2015 American Heart Association, Inc.)
Databáze:	MEDLINE
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