Stiffness of Left Ventricular Cardiac Fibroblasts Is Associated With Ventricular Dilation in Patients With Recent-Onset Nonischemic and Nonvalvular Cardiomyopathy

Abstract

Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp (LV) dilation. 1 This subgroup (ie, those with dilated cardiomyopathy: DCM) constitutes the third most common type of heart failure and is the most frequent indication for heart transplantation. 2 Etiological aspects of LV dilation in DCM are under intense current investigation. 3-5 Among other factors, imbalance in the cardiac extracellular matrix (ECM) is believed to be a key pathogenic factor of ventricular chamber dilation in heart failure. This includes increased accumulation of collagens, disturbance in ECM-regulating factors such as metalloecent-onset cardiomyopathy (ROCM), described as nonischemic and nonvalvular ventricular dysfunction with cardiac symptoms of less than 6 months' duration, is a relevant cause of heart failure and includes increased morbidity and mortality. 1 Patients with ROCM show great variation in the clinical course, which ranges from sufficient myocardial recovery to end-stage heart failure and increased mortality. Background: Ventricular dilation is known as a pivotal predictor in recent-onset cardiomyopathy (ROCM), but its pathophysiology is not fully understood. In the present study we investigated whether single-cell stiffness of right and left ventricular-derived fibroblasts has an effect on cardiac phenotype in patients with ROCM.

The stiffness‐controlled release of interleukin‐6 by cardiac fibroblasts is dependent on integrin α2β1

“…To explain the effect of the substrate stiffness on cardiac fibroblasts, polyacrylamide gels of varying stiffness were created 28,29 . A softer gel with an average Young's modulus of 2.23 ± 0.8 kPa was formed by the addition of 0.06% of bis‐acrylamide; its elasticity corresponds to the rigidity of the cardiac fibroblasts isolated from the left ventricle possessing Young's modulus of 3.38 ± 0.39 kPa 30 . A more rigid gel with Young's modulus of 8.28 ± 1.06 kPa was also created using 0.1% of bis‐acrylamide; its rigidity markedly exceeded the elasticity of the heart fibroblasts.…”

3D Micropillars Guide the Mechanobiology of Human Induced Pluripotent Stem Cell‐Derived Cardiomyocytes

“…Data Analysis : To resolve cell local Young's modulus E, force–displacement curves were analyzed using an in‐house script and the simple Hertz model as previously described . All data on elasticity measurement were expressed as means ± SE.…”

Human neutrophil antigen‐3a antibodies induce neutrophil stiffening and conformational activation of CD11b without shedding of L‐selectin

“…In this study we show that HNA‐3a antibodies, besides triggering neutrophil aggregation, also induce stiffening of neutrophils and activation of CD11b. We have recently applied AFM to characterize cell stiffness of ventricular fibroblasts from patients with recent‐onset cardiomyopathy . We now used this single‐cell AFM technique to assess the impact of HNA‐3a antibodies on the elasticity of neutrophils.…”

“…We have recently applied AFM to characterize cell stiffness of ventricular fibroblasts from patients with recent-onset cardiomyopathy. 32 We now used this single-cell AFM technique to assess the impact of HNA-3a antibodies on the elasticity of neutrophils. This allowed us to overcome the problem that HNA-3a antibodies induce neutrophil aggregation, which interferes with migration investigation using classic transmigration assays.…”