Effect of ovariectomy on cardiac gene expression: Inflammation and changes in SOCS gene expression

Karyn L. Hamilton, Li Lin, Yin Wang, Anne A Knowlton

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Basic research on estrogen-related changes in cardiomyocyte gene expression is needed to provide a greater understanding of the effects of estrogen, so that hormone replacement trials and treatment can be based on a true comprehension of estrogen's pleiotropic effects. Therefore, we compared gene expression in models of estrogen depletion and estrogen replacement. Using gene expression array analysis, we examined differences in expression in cardiac tissue from ovariectomized (OVX), ovariectomized with 17β-estradiol replacement (OVX/E2), and intact rats undergoing sham procedures (Sham). We found that OVX results in at least twofold changes in expression of genes involved in inflammation, vascular tone, apoptosis, and proteolysis compared with OVX/E2. With confirmation via real-time PCR, we found an OVX-induced increase in genes mediating inflammation (inhibin βa, IL-6, TNF-α, SOCS2, SOCS3), an OVX-related decrease in the myocardial mRNA expression of genes involved in regulating vasodilation (endothelial NOS, soluble guanyl cyclase), an OVX-associated increase in extracellular matrix genes (collagen12alpha1, connexin 43), and an OVX-related increase in proapoptotic genes (caspase 3, calpain). Because details of cardiac signaling by SOCS genes are virtually unknown, we examined the protein expression for these genes via Western analyses. Although we observed OVX-related increases in SOCS2 and SOCS3 mRNA, SOCS2 and SOCS3 protein did not differ among groups. In light of these findings, investigation into the net effect of OVX on inflammation is warranted. These experiments add to existing evidence that estrogen can protect against negative changes associated with estrogen removal.

Original languageEnglish (US)
Pages (from-to)254-263
Number of pages10
JournalPhysiological Genomics
Volume32
Issue number2
DOIs
StatePublished - Jan 17 2008

Fingerprint

Ovariectomy
Estrogens
Inflammation
Gene Expression
Genes
Messenger RNA
Connexin 43
Inhibins
Estrogen Replacement Therapy
Calpain
Guanylate Cyclase
Cardiac Myocytes
Vasodilation
Caspase 3
Proteolysis
Extracellular Matrix
Blood Vessels
Real-Time Polymerase Chain Reaction
Estradiol
Interleukin-6

Keywords

  • Cardiovascular
  • Cytokine
  • Estrogen
  • Menopause

ASJC Scopus subject areas

  • Physiology
  • Genetics

Cite this

Effect of ovariectomy on cardiac gene expression : Inflammation and changes in SOCS gene expression. / Hamilton, Karyn L.; Lin, Li; Wang, Yin; Knowlton, Anne A.

In: Physiological Genomics, Vol. 32, No. 2, 17.01.2008, p. 254-263.

Research output: Contribution to journalArticle

@article{2f3f662d2fd645beabe8402c4ad69a49,
title = "Effect of ovariectomy on cardiac gene expression: Inflammation and changes in SOCS gene expression",
abstract = "Basic research on estrogen-related changes in cardiomyocyte gene expression is needed to provide a greater understanding of the effects of estrogen, so that hormone replacement trials and treatment can be based on a true comprehension of estrogen's pleiotropic effects. Therefore, we compared gene expression in models of estrogen depletion and estrogen replacement. Using gene expression array analysis, we examined differences in expression in cardiac tissue from ovariectomized (OVX), ovariectomized with 17β-estradiol replacement (OVX/E2), and intact rats undergoing sham procedures (Sham). We found that OVX results in at least twofold changes in expression of genes involved in inflammation, vascular tone, apoptosis, and proteolysis compared with OVX/E2. With confirmation via real-time PCR, we found an OVX-induced increase in genes mediating inflammation (inhibin βa, IL-6, TNF-α, SOCS2, SOCS3), an OVX-related decrease in the myocardial mRNA expression of genes involved in regulating vasodilation (endothelial NOS, soluble guanyl cyclase), an OVX-associated increase in extracellular matrix genes (collagen12alpha1, connexin 43), and an OVX-related increase in proapoptotic genes (caspase 3, calpain). Because details of cardiac signaling by SOCS genes are virtually unknown, we examined the protein expression for these genes via Western analyses. Although we observed OVX-related increases in SOCS2 and SOCS3 mRNA, SOCS2 and SOCS3 protein did not differ among groups. In light of these findings, investigation into the net effect of OVX on inflammation is warranted. These experiments add to existing evidence that estrogen can protect against negative changes associated with estrogen removal.",
keywords = "Cardiovascular, Cytokine, Estrogen, Menopause",
author = "Hamilton, {Karyn L.} and Li Lin and Yin Wang and Knowlton, {Anne A}",
year = "2008",
month = "1",
day = "17",
doi = "10.1152/physiolgenomics.00039.2007",
language = "English (US)",
volume = "32",
pages = "254--263",
journal = "Physiological Genomics",
issn = "1094-8341",
publisher = "American Physiological Society",
number = "2",

}

TY - JOUR

T1 - Effect of ovariectomy on cardiac gene expression

T2 - Inflammation and changes in SOCS gene expression

AU - Hamilton, Karyn L.

AU - Lin, Li

AU - Wang, Yin

AU - Knowlton, Anne A

PY - 2008/1/17

Y1 - 2008/1/17

N2 - Basic research on estrogen-related changes in cardiomyocyte gene expression is needed to provide a greater understanding of the effects of estrogen, so that hormone replacement trials and treatment can be based on a true comprehension of estrogen's pleiotropic effects. Therefore, we compared gene expression in models of estrogen depletion and estrogen replacement. Using gene expression array analysis, we examined differences in expression in cardiac tissue from ovariectomized (OVX), ovariectomized with 17β-estradiol replacement (OVX/E2), and intact rats undergoing sham procedures (Sham). We found that OVX results in at least twofold changes in expression of genes involved in inflammation, vascular tone, apoptosis, and proteolysis compared with OVX/E2. With confirmation via real-time PCR, we found an OVX-induced increase in genes mediating inflammation (inhibin βa, IL-6, TNF-α, SOCS2, SOCS3), an OVX-related decrease in the myocardial mRNA expression of genes involved in regulating vasodilation (endothelial NOS, soluble guanyl cyclase), an OVX-associated increase in extracellular matrix genes (collagen12alpha1, connexin 43), and an OVX-related increase in proapoptotic genes (caspase 3, calpain). Because details of cardiac signaling by SOCS genes are virtually unknown, we examined the protein expression for these genes via Western analyses. Although we observed OVX-related increases in SOCS2 and SOCS3 mRNA, SOCS2 and SOCS3 protein did not differ among groups. In light of these findings, investigation into the net effect of OVX on inflammation is warranted. These experiments add to existing evidence that estrogen can protect against negative changes associated with estrogen removal.

AB - Basic research on estrogen-related changes in cardiomyocyte gene expression is needed to provide a greater understanding of the effects of estrogen, so that hormone replacement trials and treatment can be based on a true comprehension of estrogen's pleiotropic effects. Therefore, we compared gene expression in models of estrogen depletion and estrogen replacement. Using gene expression array analysis, we examined differences in expression in cardiac tissue from ovariectomized (OVX), ovariectomized with 17β-estradiol replacement (OVX/E2), and intact rats undergoing sham procedures (Sham). We found that OVX results in at least twofold changes in expression of genes involved in inflammation, vascular tone, apoptosis, and proteolysis compared with OVX/E2. With confirmation via real-time PCR, we found an OVX-induced increase in genes mediating inflammation (inhibin βa, IL-6, TNF-α, SOCS2, SOCS3), an OVX-related decrease in the myocardial mRNA expression of genes involved in regulating vasodilation (endothelial NOS, soluble guanyl cyclase), an OVX-associated increase in extracellular matrix genes (collagen12alpha1, connexin 43), and an OVX-related increase in proapoptotic genes (caspase 3, calpain). Because details of cardiac signaling by SOCS genes are virtually unknown, we examined the protein expression for these genes via Western analyses. Although we observed OVX-related increases in SOCS2 and SOCS3 mRNA, SOCS2 and SOCS3 protein did not differ among groups. In light of these findings, investigation into the net effect of OVX on inflammation is warranted. These experiments add to existing evidence that estrogen can protect against negative changes associated with estrogen removal.

KW - Cardiovascular

KW - Cytokine

KW - Estrogen

KW - Menopause

UR - http://www.scopus.com/inward/record.url?scp=38749120250&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38749120250&partnerID=8YFLogxK

U2 - 10.1152/physiolgenomics.00039.2007

DO - 10.1152/physiolgenomics.00039.2007

M3 - Article

C2 - 17986523

AN - SCOPUS:38749120250

VL - 32

SP - 254

EP - 263

JO - Physiological Genomics

JF - Physiological Genomics

SN - 1094-8341

IS - 2

ER -