Prostaglandins mediate the cardioprotective effects of atorvastatin against ischemia-reperfusion injury

Yochai Birnbaum, Yumei Ye, Salvatore Rosanio, Shahin Tavackoli, Zhao Yong Hu, Ernst R. Schwarz, Barry F. Uretsky

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

Statins attenuate myocardial ischemic injury by activating nitric oxide synthase (NOS). It is unknown whether cyclooxygenase-2 (COX2), which mediates late ischemic preconditioning, also mediates statins-induced cardioprotection. We investigated the involvement of the prostaglandins and NOS in the cardioprotective effect of atorvastatin (ATV) in the rat. Sprague-Dawley rats were randomized to a 3-day oral treatment with ATV 10 mg/kg, valdecoxib, a selective COX2 inhibitor (VAL) 3 mg/kg, ATV+VAL or water alone. Rats underwent 30-min myocardial ischemia followed by 4-h reperfusion. Infarct size was smaller in the ATV group (31.3±1.9%) than controls (44.5±3.1%; p=0.011) and VAL (44.5±3.1%; p=0.008). VAL attenuated the protective effect of ATV when administered together (40.2±2.5%). ATV pretreatment increased myocardial content of 6-keto-PGF (69.5±1.5 pg/mg) and PGE 2 (57.9±0.6 pg/mg) compared with controls (16.2±0.2 and 42.1±2.0 pg/mg, respectively) and ATV+VAL (15.8±0.3 and 39.9±1.9 pg/mg, respectively). ATV increased myocardial content of cytosolic phospholipase A 2 (cPLA 2) (174.8±0.5%), COX2 (446.2±0.9%), PGI 2 synthase (201.8±1.1%) and PGE 2 synthase (122±0.7%), whereas ATV+VAL did not (123.0±7.9%, 93.8±8.5%, 103.0±1.6% and 99.0±0%, respectively). ATV did not change the myocardial content of eNOS and nNOS, but increased the concentration of phosphorylated eNOS (231.8±2.4%) and iNOS (154.5±1.2%). This effect was not blocked by coadministration of VAL (231.5±3.0% and 154.5±1.8%, respectively). Our results suggest that the prostaglandins are essential for mediating the myocardial protective effects of ATV and their production is downstream to eNOS phosphorylation and iNOS.

Original languageEnglish (US)
Pages (from-to)345-355
Number of pages11
JournalCardiovascular Research
Volume65
Issue number2
DOIs
StatePublished - Feb 1 2005
Externally publishedYes

Fingerprint

Reperfusion Injury
Prostaglandins
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Cyclooxygenase 2
Prostaglandins E
Nitric Oxide Synthase
Atorvastatin Calcium
Ischemic Preconditioning
Phospholipases A
Cyclooxygenase 2 Inhibitors
Prostaglandins F
Reperfusion
Myocardial Ischemia
Sprague Dawley Rats
Phosphorylation
Control Groups
Water

Keywords

  • Cyclooxygenase
  • Infarction
  • Phospholipases
  • Prostaglandins
  • Statins

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Prostaglandins mediate the cardioprotective effects of atorvastatin against ischemia-reperfusion injury. / Birnbaum, Yochai; Ye, Yumei; Rosanio, Salvatore; Tavackoli, Shahin; Hu, Zhao Yong; Schwarz, Ernst R.; Uretsky, Barry F.

In: Cardiovascular Research, Vol. 65, No. 2, 01.02.2005, p. 345-355.

Research output: Contribution to journalArticle

Birnbaum, Yochai ; Ye, Yumei ; Rosanio, Salvatore ; Tavackoli, Shahin ; Hu, Zhao Yong ; Schwarz, Ernst R. ; Uretsky, Barry F. / Prostaglandins mediate the cardioprotective effects of atorvastatin against ischemia-reperfusion injury. In: Cardiovascular Research. 2005 ; Vol. 65, No. 2. pp. 345-355.
@article{2ce721cd73184d82b3bae540cae54ec1,
title = "Prostaglandins mediate the cardioprotective effects of atorvastatin against ischemia-reperfusion injury",
abstract = "Statins attenuate myocardial ischemic injury by activating nitric oxide synthase (NOS). It is unknown whether cyclooxygenase-2 (COX2), which mediates late ischemic preconditioning, also mediates statins-induced cardioprotection. We investigated the involvement of the prostaglandins and NOS in the cardioprotective effect of atorvastatin (ATV) in the rat. Sprague-Dawley rats were randomized to a 3-day oral treatment with ATV 10 mg/kg, valdecoxib, a selective COX2 inhibitor (VAL) 3 mg/kg, ATV+VAL or water alone. Rats underwent 30-min myocardial ischemia followed by 4-h reperfusion. Infarct size was smaller in the ATV group (31.3±1.9{\%}) than controls (44.5±3.1{\%}; p=0.011) and VAL (44.5±3.1{\%}; p=0.008). VAL attenuated the protective effect of ATV when administered together (40.2±2.5{\%}). ATV pretreatment increased myocardial content of 6-keto-PGF 1α (69.5±1.5 pg/mg) and PGE 2 (57.9±0.6 pg/mg) compared with controls (16.2±0.2 and 42.1±2.0 pg/mg, respectively) and ATV+VAL (15.8±0.3 and 39.9±1.9 pg/mg, respectively). ATV increased myocardial content of cytosolic phospholipase A 2 (cPLA 2) (174.8±0.5{\%}), COX2 (446.2±0.9{\%}), PGI 2 synthase (201.8±1.1{\%}) and PGE 2 synthase (122±0.7{\%}), whereas ATV+VAL did not (123.0±7.9{\%}, 93.8±8.5{\%}, 103.0±1.6{\%} and 99.0±0{\%}, respectively). ATV did not change the myocardial content of eNOS and nNOS, but increased the concentration of phosphorylated eNOS (231.8±2.4{\%}) and iNOS (154.5±1.2{\%}). This effect was not blocked by coadministration of VAL (231.5±3.0{\%} and 154.5±1.8{\%}, respectively). Our results suggest that the prostaglandins are essential for mediating the myocardial protective effects of ATV and their production is downstream to eNOS phosphorylation and iNOS.",
keywords = "Cyclooxygenase, Infarction, Phospholipases, Prostaglandins, Statins",
author = "Yochai Birnbaum and Yumei Ye and Salvatore Rosanio and Shahin Tavackoli and Hu, {Zhao Yong} and Schwarz, {Ernst R.} and Uretsky, {Barry F.}",
year = "2005",
month = "2",
day = "1",
doi = "10.1016/j.cardiores.2004.10.018",
language = "English (US)",
volume = "65",
pages = "345--355",
journal = "Cardiovascular Research",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - Prostaglandins mediate the cardioprotective effects of atorvastatin against ischemia-reperfusion injury

AU - Birnbaum, Yochai

AU - Ye, Yumei

AU - Rosanio, Salvatore

AU - Tavackoli, Shahin

AU - Hu, Zhao Yong

AU - Schwarz, Ernst R.

AU - Uretsky, Barry F.

PY - 2005/2/1

Y1 - 2005/2/1

N2 - Statins attenuate myocardial ischemic injury by activating nitric oxide synthase (NOS). It is unknown whether cyclooxygenase-2 (COX2), which mediates late ischemic preconditioning, also mediates statins-induced cardioprotection. We investigated the involvement of the prostaglandins and NOS in the cardioprotective effect of atorvastatin (ATV) in the rat. Sprague-Dawley rats were randomized to a 3-day oral treatment with ATV 10 mg/kg, valdecoxib, a selective COX2 inhibitor (VAL) 3 mg/kg, ATV+VAL or water alone. Rats underwent 30-min myocardial ischemia followed by 4-h reperfusion. Infarct size was smaller in the ATV group (31.3±1.9%) than controls (44.5±3.1%; p=0.011) and VAL (44.5±3.1%; p=0.008). VAL attenuated the protective effect of ATV when administered together (40.2±2.5%). ATV pretreatment increased myocardial content of 6-keto-PGF 1α (69.5±1.5 pg/mg) and PGE 2 (57.9±0.6 pg/mg) compared with controls (16.2±0.2 and 42.1±2.0 pg/mg, respectively) and ATV+VAL (15.8±0.3 and 39.9±1.9 pg/mg, respectively). ATV increased myocardial content of cytosolic phospholipase A 2 (cPLA 2) (174.8±0.5%), COX2 (446.2±0.9%), PGI 2 synthase (201.8±1.1%) and PGE 2 synthase (122±0.7%), whereas ATV+VAL did not (123.0±7.9%, 93.8±8.5%, 103.0±1.6% and 99.0±0%, respectively). ATV did not change the myocardial content of eNOS and nNOS, but increased the concentration of phosphorylated eNOS (231.8±2.4%) and iNOS (154.5±1.2%). This effect was not blocked by coadministration of VAL (231.5±3.0% and 154.5±1.8%, respectively). Our results suggest that the prostaglandins are essential for mediating the myocardial protective effects of ATV and their production is downstream to eNOS phosphorylation and iNOS.

AB - Statins attenuate myocardial ischemic injury by activating nitric oxide synthase (NOS). It is unknown whether cyclooxygenase-2 (COX2), which mediates late ischemic preconditioning, also mediates statins-induced cardioprotection. We investigated the involvement of the prostaglandins and NOS in the cardioprotective effect of atorvastatin (ATV) in the rat. Sprague-Dawley rats were randomized to a 3-day oral treatment with ATV 10 mg/kg, valdecoxib, a selective COX2 inhibitor (VAL) 3 mg/kg, ATV+VAL or water alone. Rats underwent 30-min myocardial ischemia followed by 4-h reperfusion. Infarct size was smaller in the ATV group (31.3±1.9%) than controls (44.5±3.1%; p=0.011) and VAL (44.5±3.1%; p=0.008). VAL attenuated the protective effect of ATV when administered together (40.2±2.5%). ATV pretreatment increased myocardial content of 6-keto-PGF 1α (69.5±1.5 pg/mg) and PGE 2 (57.9±0.6 pg/mg) compared with controls (16.2±0.2 and 42.1±2.0 pg/mg, respectively) and ATV+VAL (15.8±0.3 and 39.9±1.9 pg/mg, respectively). ATV increased myocardial content of cytosolic phospholipase A 2 (cPLA 2) (174.8±0.5%), COX2 (446.2±0.9%), PGI 2 synthase (201.8±1.1%) and PGE 2 synthase (122±0.7%), whereas ATV+VAL did not (123.0±7.9%, 93.8±8.5%, 103.0±1.6% and 99.0±0%, respectively). ATV did not change the myocardial content of eNOS and nNOS, but increased the concentration of phosphorylated eNOS (231.8±2.4%) and iNOS (154.5±1.2%). This effect was not blocked by coadministration of VAL (231.5±3.0% and 154.5±1.8%, respectively). Our results suggest that the prostaglandins are essential for mediating the myocardial protective effects of ATV and their production is downstream to eNOS phosphorylation and iNOS.

KW - Cyclooxygenase

KW - Infarction

KW - Phospholipases

KW - Prostaglandins

KW - Statins

UR - http://www.scopus.com/inward/record.url?scp=11444251238&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=11444251238&partnerID=8YFLogxK

U2 - 10.1016/j.cardiores.2004.10.018

DO - 10.1016/j.cardiores.2004.10.018

M3 - Article

VL - 65

SP - 345

EP - 355

JO - Cardiovascular Research

JF - Cardiovascular Research

SN - 0008-6363

IS - 2

ER -