Myocardial tissue elastic properties determined by atomic force microscopy after stromal cell–derived factor 1α angiogenic therapy for acute myocardial infarction in a murine model

Abstract

BACKGROUND Ventricular remodeling after myocardial infarction begins with massive extracellular matrix deposition and resultant fibrosis. This loss of functional tissue and the stiffening of myocardial elastic and contractile elements starts the vicious cycle of mechanical inefficiency, adverse remodeling, and eventual heart failure. We hypothesize that SDF-1α therapy to microrevascularize ischemic myocardium will rescue salvageable peri-infarct tissue and subsequently improve myocardial elasticity. METHODS Immediately following LAD ligation, mice were randomized to receive peri-infarct injection of either saline or SDF. After six weeks, the animals were sacrificed and samples were taken from the peri-infarct borderzone, the infarct scar, and the left ventricle of non-infarcted control mice. Determination of the tissues’ elastic moduli was carried out by mechanical testing in an atomic force microscope. RESULTS SDF treated peri-infarct tissue most closely approximated the elasticity of normal ventricle and was significantly more elastic than saline treated myocardium (109 + 22.9 kPa vs. 295 + 42.3 kPa, p < 0.0001). The myocardial scar, the strength of which depends on matrix deposition from vasculature at the peri-infarct edge, was stiffer in SDF treated animals when compared to controls (804 + 102.2 kPa vs. 144 + 27.5 kPa, p < 0.0001). CONCLUSIONS This study, through direct quantification of myocardial elastic properties, has demonstrated the ability of SDF to re-engineer the evolving myocardial infarct and peri-infarct tissue. By increasing the elasticity of the ischemic and dysfunctional peri-infarct borderzone and bolstering the weak aneurysm prone scar, SDF therapy may confer a mechanical advantage to resist adverse remodeling following infarction.

Noncontact quantitative biomechanical characterization of cardiac muscle using shear wave imaging optical coherence tomography

“…Compared with AFM that has been generally used in cardiac tissue research with cellular level detection [47], SWI-OCT probes the group elastic effect of the cardiomyocytes that we believe can provide new information regarding the heart biomechanics, as an important assistance for better understanding of the properties of cardiac muscle. Also, the measurement scale and the procedure of SWI-OCT enable the potential studies of myocardium elasticity under different cardiomyosite status, such as during cell contraction and with different cardiomyosite directions, which are of great importance for the mechanical tests of regenerated or engineered cardiac muscle tissues.…”

The (dys)functional extracellular matrix

“…Increased elastic modulus of infarcted versus non-infarcted tissue and the border zone myocardium were found in a rat model of ischemic cardiomyopathy (Table 2). Increased stiffness was also observed in the peri-infarct zone in a mouse infarction model [169]. The extension of adverse biomechanical remodeling beyond the infarct zone is well known to be central to the development of HF.…”

The soft mechanical signature of glial scars in the central nervous system

“…In adult higher vertebrates, which cannot regenerate most of their organs, injuries often lead to fibrosis, and wounds result in some degree of scarring. Scars are typically rich in strongly cross-linked collagen-1, and as the amount of collagen-1 determines the stiffness of a tissue1, scars are normally considerably stiffer than healthy tissue in a variety of organs23, including skin45, heart678, blood vessel9 and liver10.…”