Methods and compositions for controlling cardiac fibrosis and remodeling

A heart, cardiology technology, applied in the field of control of myocardial fibrosis and remodeling and composition

Pending Publication Date: 2020-04-17
UNIVERSITY OF LAUSANNE
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Antifibrotic agents, including blockers of the renin-angiotensin-aldosterone system (RAAS) and mineralocorticoid receptor antagonists, are ineffective in most fibrotic disorders (5)

Method used

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  • Methods and compositions for controlling cardiac fibrosis and remodeling
  • Methods and compositions for controlling cardiac fibrosis and remodeling
  • Methods and compositions for controlling cardiac fibrosis and remodeling

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0137] Materials and methods

[0138] Primary cell culture and transfection

[0139] CM and fibroblast isolation from neonatal mice: Neonatal C57B6 mice were sacrificed within 24 h after birth, and beating hearts were harvested. Carefully excise the atria and great vessels and place them on ice in ADS buffer (H 2 O, NaCl 116mM, HEPES 20mM, NaH 2 PO 4 1mM, KCl 5.4mM, MgSO 4 0.8mM, glucose 5.5mM). Mince the heart using a sterile sharp blade and place the heart in 1.5 ml of PIB digestion buffer (ADS buffer; 0.05 mg / ml collagenase type II (Worthington); 1 mg / ml trypsin; Sigma). ml tubes (5-6 hearts per tube). The tissue was incubated with shaking at 37°C for 15 minutes. Then the supernatant was collected in a medium containing complete medium (DMEM 75%, M199 25% ml, penicillin / streptavidin 1x, L-glutamine 1x, horse serum 10%, fetal bovine serum 5%; Gibco ) in the tube. PIB buffer was added to undigested tissue fragments and digestion was repeated twice. Cells were harv...

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Abstract

The present invention provides methods and compositions for controlling cardiac fibrosis and heart remodeling in a subject via modulating the expression of one or more lncRNA associated with cardiac-specific super-enhancers (SEs).

Description

technical field [0001] The present invention provides methods and compositions for controlling myocardial fibrosis and cardiac remodeling in a subject by modulating the expression of one or more lncRNAs associated with cardiac-specific super-enhancers (SE). Background technique [0002] Acute myocardial infarction (MI) due to coronary artery disease often results in maladaptive myocardial remodeling and heart failure (HF) (1,2). HF imposes an enormous economic and clinical burden on industrialized countries, and in the United States alone, HF is responsible for more than 400,000 deaths and more than $20 billion in healthcare costs annually (3). Initial translational research has focused on the heart's contractile cells, the cardiomyocytes (CMs), as targets for therapeutic approaches aimed at restoring myocardial function. Despite the widespread belief that acute and chronic injury trigger tissue remodeling, this invariably leads to and ultimately contributes to the developm...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00C12N15/113A61K31/7088C12N15/63
CPCA61K31/7088C12N15/113C12N2310/11A61P9/00C12N2310/20C12N9/22C12N2310/141
Inventor S·奥扎因T·佩德拉齐尼
Owner UNIVERSITY OF LAUSANNE
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