Effect of Heme Oxygenase-1 on the smooth muscle cells growth

the biological function of heme oxygena

se

Heme oxygenase

+

heme

Biliverdin Bilirubin

Fe2+ CO

three isoforms of heme oxygenase (HO)

HO-1 : an inducible isoform

HO-2: a constitutive isoform

HO-3: closely resembles HO-2

hypoxia

UV radition

IL-10NO

15-PGJ2

Heat shock proteins

Protection effect of HO-1 by many mechnisms

Anti-

inflammation

Anti-apoptotisis Anti-

proliferation

the effect of HO-1 on the smooth muscle cells growth

Hmox1–/–

Hmox1+/+

HO-1 gene deletion (Hmox1-/-) results in enhanced cell growth

+

SMC

Transfer AdHO-1 (adenovirus containing the rat HO-1 gene) to SMCs

AdHO-1 HO-1

2% serum 5% serum

Infection of SMCs with AdHO-1 inhibit the proliferative response to serum in a concentration-dependent manner

Mechanism Ⅰ

HO-1 blocks the proliferation of vascular SMCs by stimulating programmed cell death

DNA laddering caspase-3 activity

DNA laddering investigate the effect of

CO and Fe on cell apoptosis

Bilirubin Production Administration of biliverdin and bilirubin

the effect of bilirubin on cell apoptosis

HO-1

Apoptosis

CO Febilirubin

AdHO-1: AdHO-1 AdHO-1 AdHO-1 AdHO-1 AdHO-1

Inhibitor: - +ZnPPIX +L-NAME +ODQ +Rp8BrcGMP

Target: - (HO-1) (NOS) (sGC) (cGMP)

[3H

] c.p

.m.

(%co

ntro

l)

Mechanism Ⅱ

Cell

num

ber

Fluorescence intensity

Control Ad-ΔE1 AdHO-1

Summary