Healthy cardiomyocytes grown on extracellular matrix from hypertrophic cardiomyopathy hearts exhibited prolonged early relaxation time (190 vs 143 ms) compared to those grown on healthy matrix.
Does diseased extracellular matrix from hypertrophic myocardium impair twitch dynamics in healthy cardiomyocytes?
Extracellular matrix abnormalities in hypertrophic cardiomyopathy directly impair cardiomyocyte contraction and relaxation, suggesting that targeting the matrix is necessary for treating established HCM.
Absolute Event Rate: 190% vs 143%
p-value: p=0.0022
Hypertrophic cardiomyopathy (HCM) is often caused by single sarcomeric gene mutations that affect muscle contraction. Pharmacological correction of mutation effects prevents but does not reverse disease in mouse models. Suspecting that diseased extracellular matrix is to blame, we obtained myocardium from a miniature swine model of HCM, decellularized thin slices of the tissue, and re-seeded them with healthy human induced pluripotent stem cell-derived cardiomyocytes. Compared with cardiomyocytes grown on healthy extracellular matrix, those grown on the diseased matrix exhibited prolonged contractions and poor relaxation. This outcome suggests that extracellular matrix abnormalities must be addressed in therapies targeting established HCM.
Sewanan et al. (Wed,) conducted a other in Hypertrophic cardiomyopathy. Diseased extracellular matrix (MYH7 R403Q mutant) vs. Healthy extracellular matrix (wild-type) was evaluated on Early relaxation time (RT50) in milliseconds (p=0.0022). Healthy cardiomyocytes grown on extracellular matrix from hypertrophic cardiomyopathy hearts exhibited prolonged early relaxation time (190 vs 143 ms) compared to those grown on healthy matrix.