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Bioengineered analog of stromal cell-derived factor 1α preserves the biaxial mechanical properties of native myocardium after infarction.
Wang, Hanjay; Wisneski, Andrew; Paulsen, Michael J; Imbrie-Moore, Annabel; Wang, Zhongjie; Xuan, Yue; Hernandez, Hector Lopez; Lucian, Haley J; Eskandari, Anahita; Thakore, Akshara D; Farry, Justin M; Hironaka, Camille E; von Bornstaedt, Daniel; Steele, Amanda N; Stapleton, Lyndsay M; Williams, Kiah M; Wu, Matthew A; MacArthur, John W; Woo, Y Joseph.
Afiliación
  • Wang H; Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA.
  • Wisneski A; Department of Surgery, University of California San Francisco, San Francisco, CA, USA.
  • Paulsen MJ; Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA.
  • Imbrie-Moore A; Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA; Department of Mechanical Engineering, Stanford University, Stanford, CA, USA.
  • Wang Z; Department of Surgery, University of California San Francisco, San Francisco, CA, USA.
  • Xuan Y; Department of Surgery, University of California San Francisco, San Francisco, CA, USA.
  • Hernandez HL; Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA.
  • Lucian HJ; Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA.
  • Eskandari A; Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA.
  • Thakore AD; Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA.
  • Farry JM; Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA.
  • Hironaka CE; Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA.
  • von Bornstaedt D; Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA.
  • Steele AN; Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA; Department of Bioengineering, Stanford University, Stanford, CA, USA.
  • Stapleton LM; Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA; Department of Bioengineering, Stanford University, Stanford, CA, USA.
  • Williams KM; Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA.
  • Wu MA; Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA.
  • MacArthur JW; Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA.
  • Woo YJ; Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA; Department of Bioengineering, Stanford University, Stanford, CA, USA. Electronic address: joswoo@stanford.edu.
J Mech Behav Biomed Mater ; 96: 165-171, 2019 08.
Article en En | MEDLINE | ID: mdl-31035067
Adverse remodeling of the left ventricle (LV) after myocardial infarction (MI) results in abnormal tissue biomechanics and impaired cardiac function, often leading to heart failure. We hypothesized that intramyocardial delivery of engineered stromal cell-derived factor 1α analog (ESA), our previously-developed supra-efficient pro-angiogenic chemokine, preserves biaxial LV mechanical properties after MI. Male Wistar rats (n = 45) underwent sham surgery (n = 15) or permanent left anterior descending coronary artery ligation. Rats sustaining MI were randomized for intramyocardial injections of either saline (100 µL, n = 15) or ESA (6 µg/kg, n = 15), delivered at four standardized borderzone sites. After 4 weeks, echocardiography was performed, and the hearts were explanted. Tensile testing of the anterolateral LV wall was performed using a displacement-controlled biaxial load frame, and modulus was determined after constitutive modeling. At 4 weeks post-MI, compared to saline controls, ESA-treated hearts had greater wall thickness (1.68 ±â€¯0.05 mm vs 1.42 ±â€¯0.08 mm, p = 0.008), smaller end-diastolic LV internal dimension (6.88 ±â€¯0.29 mm vs 7.69 ±â€¯0.22 mm, p = 0.044), and improved ejection fraction (62.8 ±â€¯3.0% vs 49.4 ±â€¯4.5%, p = 0.014). Histologic analysis revealed significantly reduced infarct size for ESA-treated hearts compared to saline controls (29.4 ±â€¯2.9% vs 41.6 ±â€¯3.1%, p = 0.021). Infarcted hearts treated with ESA exhibited decreased modulus compared to those treated with saline in both the circumferential (211.5 ±â€¯6.9 kPa vs 264.3 ±â€¯12.5 kPa, p = 0.001) and longitudinal axes (194.5 ±â€¯6.5 kPa vs 258.1 ±â€¯14.4 kPa, p < 0.001). In both principal directions, ESA-treated infarcted hearts possessed similar tissue compliance as sham non-infarcted hearts. Overall, intramyocardial ESA therapy improves post-MI ventricular remodeling and function, reduces infarct size, and preserves native LV biaxial mechanical properties.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Ingeniería de Proteínas / Quimiocina CXCL12 / Fenómenos Mecánicos / Corazón / Infarto del Miocardio Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Mech Behav Biomed Mater Asunto de la revista: ENGENHARIA BIOMEDICA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Ingeniería de Proteínas / Quimiocina CXCL12 / Fenómenos Mecánicos / Corazón / Infarto del Miocardio Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Mech Behav Biomed Mater Asunto de la revista: ENGENHARIA BIOMEDICA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos