当前位置： SCI文献检索 > JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY期刊下所有文献 > Myofibroblast Phenotype and Reversibility of Fibrosis in Patients With End-Stage Heart Failure.

Myofibroblast Phenotype and Reversibility of Fibrosis in Patients With End-Stage Heart Failure.

Abstract：

BACKGROUND:Interstitial fibrosis is an important component of diastolic, and systolic, dysfunction in heart failure (HF) and depends on activation and differentiation of fibroblasts into myofibroblasts (MyoFb). Recent clinical evidence suggests that in late-stage HF, fibrosis is not reversible. OBJECTIVES:The study aims to examine the degree of differentiation of cardiac MyoFb in end-stage HF and the potential for their phenotypic reversibility. METHODS:Fibroblasts were isolated from the left ventricle of the explanted hearts of transplant recipients (ischemic and dilated cardiomyopathy), and from nonused donor hearts. Fibroblasts were maintained in culture without passaging for 4 or 8 days (treatment studies). Phenotyping included functional testing, immunostaining, and expression studies for markers of differentiation. These data were complemented with immunohistology and expression studies in tissue samples. RESULTS:Interstitial fibrosis with cross-linked collagen is prominent in HF hearts, with presence of activated MyoFbs. Tissue levels of transforming growth factor (TGF)-β1, lysyl oxidase, periostin, and osteopontin are elevated. Fibroblastic cells isolated from HF hearts are predominantly MyoFb, proliferative or nonproliferative, with mature α-smooth muscle actin stress fibers. HF MyoFb express high levels of profibrotic cytokines and the TGF-β1 pathway is activated. Inhibition of TGF-β1 receptor kinase in HF MyoFb promotes dedifferentiation of MyoFb with loss of α-smooth muscle actin and depolymerization of stress fibers, and reduces the expression of profibrotic genes and cytokines levels to non-HF levels. CONCLUSION:MyoFb in end-stage HF have a variable degree of differentiation and retain the capacity to return to a less activated state, validating the potential for developing antifibrotic therapy targeting MyoFb.

journal_name

J Am Coll Cardiol

journal_title

Journal of the American College of Cardiology

authors

Nagaraju CK,Robinson EL,Abdesselem M,Trenson S,Dries E,Gilbert G,Janssens S,Van Cleemput J,Rega F,Meyns B,Roderick HL,Driesen RB,Sipido KR

doi

10.1016/j.jacc.2019.02.049

subject

Has Abstract

pub_date

2019-05-14 00:00:00

pages

2267-2282

issue

eissn

0735-1097

issn

1558-3597

pii

S0735-1097(19)34430-4

journal_volume

pub_type

杂志文章

在线工具

Myofibroblast Phenotype and Reversibility of Fibrosis in Patients With End-Stage Heart Failure.