Abstract
No effective medical treatment exists for heart failure with preserved ejection fraction (HFpEF), accounting for approximately half of all heart failure cases. The elevated passive myocardial stiffness in HFpEF is attributed to a combination of alterations in the extracellular matrix (ECM) collagen content and modifications in the sarcomeric protein titin. Here, we propose polylaminin, a biomimetic polymer of laminin, as a promising approach for manipulating the titin isoform shift and phosphorylation in cardiomyocytes. Exploring the pleiotropic effects of polylaminin may be a novel strategy for alleviating symptoms in HFpEF’s multifactorial pathophysiology.
Highlights
Heart failure (HF) is a final common pathway for many cardiovascular diseases
Because alterations alterations in in titin titin isoform isoform expression expression can can modulate modulate stiffness, stiffness, we we reasoned reasoned that that manipulating manipulatingbasement basementmembrane membraneproteins, proteins, specificallylaminin, laminin,could couldalter altercardiomyocyte cardiomyocytestiffness
End, our our group’s group’s preliminary preliminary in in vitro and ex vivo data show that modulating modulating basement basement membrane membrane laminin laminin isoforms isoforms can can alter alter gene gene expression—titin expression—titin isoform isoform expression, expression, —in —in human human induced induced pluripotent pluripotent stem stem cell cell-derived-derived cardiomyocytes
Summary
Heart failure (HF) is a final common pathway for many cardiovascular diseases. Around half of the HF population has heart failure with preserved ejection fraction (HFpEF), and its prevalence will likely grow with the increased age and longevity of the population. The hallmark pathophysiological finding with HFpEF is reduced cardiac compliance and increased diastolic passive stiffness. Because alterations alterations in in titin titin isoform isoform expression expression can can modulate modulate stiffness, stiffness, we we reasoned reasoned that that manipulating manipulatingbasement basementmembrane membraneproteins, proteins, specificallylaminin, laminin,could couldalter altercardiomyocyte cardiomyocytestiffness. To this this end, end, our our group’s group’s preliminary preliminary in in vitro and ex vivo data show that modulating modulating basement basement membrane membrane laminin laminin isoforms isoforms can can alter alter gene gene expression—titin expression—titin isoform isoform expression, expression, —in —in human human induced induced pluripotent pluripotent stem stem cell cell (hiPSC)-derived (hiPSC)-derived cardiomyocytes.
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