Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Inhibition of histone deacetylase as a treatment for cardiac hypertrophy

a technology of histone deacetylase and cardiac hypertrophy, which is applied in the field of development biology and molecular biology, can solve the problems of cardiac hypertrophy, which is still not fully understood, and achieve the effects of improving one or more symptoms of cardiac failure, increasing exercise capacity, and increasing blood ejection volum

Inactive Publication Date: 2006-02-02
LONG CARLIN +3
View PDF7 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

"The present invention provides a method for treating cardiac hypertrophy and heart failure by administering a histone deacetylase inhibitor to a patient. The treatment may improve symptoms of cardiac failure such as exercise capacity, blood ejection volume, and left ventricular end diastolic pressure. The method may involve administering the histone deacetylase inhibitor through various routes such as intravenous, oral, transdermal, or suppository. The invention also provides a method for identifying inhibitors of cardiac hypertrophy by measuring the expression of one or more cardiac hypertrophy parameters in a myocyte treated with the histone deacetylase inhibitor. The one or more cardiac hypertrophy parameters may include the expression level of target genes such as ANF, α-MyHC, β-MyHC, α-skeletal actin, or insulin growth factor binding protein. The invention provides a novel approach for treating cardiac hypertrophy and heart failure by targeting the underlying pathophysiological mechanism of the disease."

Problems solved by technology

All of these signals activate MEF2 and result in cardiac hypertrophy.
However, it is still not completely understood how the various signal systems exert their effects on MEF2 and modulate its hypertrophic signaling.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Inhibition of histone deacetylase as a treatment for cardiac hypertrophy
  • Inhibition of histone deacetylase as a treatment for cardiac hypertrophy
  • Inhibition of histone deacetylase as a treatment for cardiac hypertrophy

Examples

Experimental program
Comparison scheme
Effect test

example 1

Materials and Methods

[0099] Cell culture. Ventricular myocytes from one-day-old rats were plated at low density in MEM with 5% calf serum, and studied in serum-free MEM. Cultures were treated with PE (#P6126, Sigma-Aldrich Corp., St. Louis, Mo.), IL-1 (#501-RL, R&D Systems, Minneapolis, Minn.), TSA (#GR-309, BIOMOL Research Laboratories, Inc., Plymouth Meeting, Pa.) or their vehicles (ascorbic acid for PE; bovine serum albumin for IL-1; dimethyl sulfoxide for TSA).

[0100] Detection of acetylated lysine residues. Total cell extract was subjected to Western blot analysis using antibodies from Cell Signaling Technology (Beverly, MA) (acetylated lysine antibody: #9441, acetylated histone H3 antibody at Lysine 9: #9671, acetylated histone H3 antibody at Lysine 23: #9674, histone H3 antibody: #9712). Nuclear localization of acetylated histone H3 was examined by immunostaining using the same antibodies.

[0101] Quantification of myocyte hypertrophy and myocyte-specific mRNA expression. Gr...

example 2

Materials and Methods

[0106] Cardiomyocyte isolation. Hearts were harvested from 15-day timed-pregnant female Sprague-Dawley rats (Harlan, Houston, Tex.). After mincing in phosphate-buffered saline, cardiomyocytes were isolated from successive digestion fractions of 0.1% (w / v) Pancreatin (Sigma, St. Louis, Mo.) solution. Fractions were collected; resuspended in plating medium, pooled; and then plated for 2 hours to separate fibroblasts from cardiomyocyte population. Suspended cells were recollected and plated in 6-well dishes at 1×106 cells / well for transfection and immunofluorescence experiments, and 2×106 cells in 10 cm dishes for RNA analysis.

[0107] Transcription assay. Twenty-four hours after plating, cells were transfected with total of 1 μg / ml for 5 hrs using Lipofectamine Plus reagent (Invitrogen, Carlsbad, Calif.). Transfected cells were incubated 24 hrs then treated for an additional 24 hrs. Cells were lysed and their lysates assayed with the Luciferase Assay System (Prom...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
cell sizeaaaaaaaaaa
massaaaaaaaaaa
timeaaaaaaaaaa
Login to View More

Abstract

The present invention provides for methods of treating and preventing cardiac hypertrophy. Class II HDACs, which are known to participate in regulation of chromatin structure and gene expression, have been shown to have beneficial effects on cardiac hypertrophy. Surprisingly, the present invention demonstrates that HDAC inhibitors inhibit cardiac hypertrophy by inhibiting fetal cardiac gene expression and interfering with sarcomeric organization.

Description

[0001] The present invention claims benefit of priority to U.S. Provisional Ser. Nos. 60 / 325,311, filed Sep. 27, 2001, and 60 / 334,041, filed Oct. 31, 2001, the entire contents of which are hereby incorporated by reference without reservation.[0002] The government owns rights in the present invention pursuant to grant number NIH RO1 HL61544 from the National Institutes of Health.BACKGROUND OF THE INVENTION [0003] 1. Field of the Invention [0004] The present invention relates generally to the fields of developmental biology and molecular biology. More particularly, it concerns gene regulation and cellular physiology in cardiomyocytes. Specifically, the invention relates to the use of HDAC inhibitors to treat cardiac hypertrophy and heart failure. [0005] 2. Description of Related Art [0006] Cardiac hypertrophy in response to an increased workload imposed on the heart is a fundamental adaptive mechanism. It is a specialized process reflecting a quantitative increase in cell size and mas...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/12A61K31/19A61K31/16A61K31/165A61K31/167A61K31/18A61K31/336A61K31/40A61K31/4402A61K31/473A61K38/00A61K45/00A61K45/06A61P9/00A61P9/04G01N33/15G01N33/50
CPCA61K31/165A61K31/19A61K31/401A61K38/12A61K45/06A61K2300/00A61P43/00A61P9/00A61P9/04A61P9/10A61P9/12
Inventor LONG, CARLINOLSON, ERICBRISTOW, MICHAELMCKINSEY, TIMOTHY
Owner LONG CARLIN
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com