Bioengineered analog of stromal cell-derived factor 1α preserves the biaxial mechanical properties of native myocardium after infarction

Hanjay Wang; Andrew Wisneski; Michael J Paulsen; Annabel Imbrie-Moore; Zhongjie Wang; Yue Xuan; Hector Lopez Hernandez; Haley J Lucian; Anahita Eskandari; Akshara D Thakore; Justin M Farry; Camille E Hironaka; Daniel von Bornstaedt; Amanda N Steele; Lyndsay M Stapleton; Kiah M Williams; Matthew A Wu; John W MacArthur Jr; Y Joseph Woo

doi:10.1016/j.jmbbm.2019.04.014

Bioengineered analog of stromal cell-derived factor 1α preserves the biaxial mechanical properties of native myocardium after infarction

J Mech Behav Biomed Mater. 2019 Aug:96:165-171. doi: 10.1016/j.jmbbm.2019.04.014. Epub 2019 Apr 17.

Authors

Hanjay Wang¹, Andrew Wisneski², Michael J Paulsen¹, Annabel Imbrie-Moore³, Zhongjie Wang², Yue Xuan², Hector Lopez Hernandez⁴, Haley J Lucian¹, Anahita Eskandari¹, Akshara D Thakore¹, Justin M Farry¹, Camille E Hironaka¹, Daniel von Bornstaedt¹, Amanda N Steele⁵, Lyndsay M Stapleton⁵, Kiah M Williams¹, Matthew A Wu¹, John W MacArthur Jr¹, Y Joseph Woo⁶

Affiliations

¹ Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA.
² Department of Surgery, University of California San Francisco, San Francisco, CA, USA.
³ Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA; Department of Mechanical Engineering, Stanford University, Stanford, CA, USA.
⁴ Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA.
⁵ Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA; Department of Bioengineering, Stanford University, Stanford, CA, USA.
⁶ Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA; Department of Bioengineering, Stanford University, Stanford, CA, USA. Electronic address: joswoo@stanford.edu.

Abstract

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 ± 0.05 mm vs 1.42 ± 0.08 mm, p = 0.008), smaller end-diastolic LV internal dimension (6.88 ± 0.29 mm vs 7.69 ± 0.22 mm, p = 0.044), and improved ejection fraction (62.8 ± 3.0% vs 49.4 ± 4.5%, p = 0.014). Histologic analysis revealed significantly reduced infarct size for ESA-treated hearts compared to saline controls (29.4 ± 2.9% vs 41.6 ± 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 ± 6.9 kPa vs 264.3 ± 12.5 kPa, p = 0.001) and longitudinal axes (194.5 ± 6.5 kPa vs 258.1 ± 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.

Keywords: Angiogenic therapy; Biaxial tension; Myocardial infarction; Ventricular remodeling.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biomechanical Phenomena / drug effects
Chemokine CXCL12 / genetics*
Chemokine CXCL12 / pharmacology*
Heart / drug effects*
Heart / physiopathology*
Male
Mechanical Phenomena / drug effects*
Myocardial Infarction / physiopathology*
Protein Engineering*
Rats
Rats, Wistar
Ventricular Remodeling / drug effects

Substances

Chemokine CXCL12

Abstract

Publication types

MeSH terms

Substances

Grants and funding