過氧化體增殖劑活化受器促進劑Rosiglitzaone對於大白鼠過度左心室後負荷所致心衰竭的心肌整體基因表現型態之影響
Other Title
Global gene expression profiling of congestive heart failure subsequent to
experimental left ventricular pressure overload pretreated with the peroxisome
proliferator-activated receptor-gama agonist Rosiglitazone
experimental left ventricular pressure overload pretreated with the peroxisome
proliferator-activated receptor-gama agonist Rosiglitazone
Date Issued
2005
Date
2005
Author(s)
黃瑞仁
DOI
932314B002224
Abstract
Aim of study: To explore the gene expression profiles of congestive heart failure (CHF)
subsequent to experimental pressure overload pretreated with peroxisome
proliferator-activated receptor-g (PPARg) agonist Rosiglitazone. And to elucidate the potential
benefits and mechanisms of PPARg agonist on pressure-overload hemodynamics, cardiac
remodeling, and CHF.
Background: Hypertension (HTN) continues to be of major public health concern. Increased
risks of several adverse neurological and cardiovascular outcomes were documented in the
population of HTN. Longstanding HTN increased the left ventricular (LV) afterload markedly,
and cardiac fibrosis evolves as an adaptive response to hemodyanamic overload. Subsequently,
interstitial fibrosis occurred and contributed to LV stiffening and impaired compliance.
Although initially the LV systolic function is well preserved with simply diastolic dysfunction,
however progression to decompenated stage congestive heart failure (CHF) with systolic
dysfunction is hastened. PPARs are nuclear receptors, which function as transcription factors
the regulate different genes expression. They control a variety of cellular functions and are
involved in control of vascular inflammation, thrombogenecity and inflammatory cytokines.
Several animal studies had shown that ligands of the PPARs can reduce infarct size and
potentially protect the heart against ischemia-reperfusion injury. PPARg ligands have also
been shown to suppress the development of cardiac myocyte hypertrophy both in vitro and in
the in vivo setting. However, knowledge about the influences of PPARs on pressure-loaded
CHF and cardiac remodeling process at cellular level is quite limited. cDNA microarray offers
a genome-wide simultaneous analysis of gene expression profiling changes in perturbed
physiological or pathological conditions. With the aid of this powerful tool, researches could
progress efficiently.
Experimental protocol: Rosiglitazone-pretreated or placebo-preteated rats undergo
abdominal aorta ligation resulting in left ventricular overload. Two-color cDNA microarray
system containing 7,600 clones from regional company is applied to explore the cardiac
differential gene expressions between Rosiglitzaone-pretreated and placebo-pretreated rat
pressure overload model. Serum biochemistry, hemodynamics, echocardiography, and clinical
conditions are also measured prior to sacrifice and will be analyzed.
Expected results: The two-color cDNA microarray data analysis will be validated utilizing
RT-PCR. Through this study, Rosigliazone pretreatment effects, whether beneficial or not, on
pressure overload cardiac remodeling and CHF course could be evaluated, and differential
cardiac gene expressions contributing to the probable beneficial effect of Rosiglitazone on CHF subsequent to pressure overload could be elucidated.
Subjects
peroxisome proliferator-activated receptor-g agonist
pressure overload
congestive heart failure
remodeling
cDNA microarray
gene expression profiling
SDGs
Publisher
臺北市：國立臺灣大學醫學院內科
Type
report
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