A novel inducible cholesterol efflux peptide, FAMP, protects against myocardial ischemia reperfusion injury through a nitric oxide pathway

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• 作者：Yasunori Suematsu^a ; Shin-ichiro Miura^a ; ^b ; ^{miuras@cis.fukuoka-u.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Kohei Takata^a ; Tomohiko Shimizu^a ; Takashi Kuwano^a ; Satoshi Imaizumi^a ; Yoshino Matsuo^a ; Eiji Yahiro^a ; Yoshinari Uehara^a ; ^b ; Keijiro Saku^a ; ^b
• 关键词：Apolipoproteins ; High-density lipoprotein ; Nitric oxide ; Anti-apoptosis
• 刊名：International Journal of Cardiology
• 出版年：2016
• 出版时间：1 January 2016
• 年：2016
• 卷：202
• 期：Complete
• 页码：810-816
• 全文大小：898 K

文摘

We evaluated whether a novel inducible cholesterol efflux (iCE) peptide [Fukuoka University Apolipoprotein A-I Mimetic Peptide (FAMP)] protects against myocardial ischemia reperfusion injury (IRI) through a nitric oxide (NO) pathway by an improvement of high-density lipoprotein (HDL) functionality.

Methods and results

Male C57BL6/J mice were intraperitoneally injected with phosphate buffer as a control, low-dose (10 mg/kg) or high-dose (50 mg/kg) of FAMP before 18 h of IRI (n = 6–12 in each group). After 30 min of ischemia followed by 6 h of reperfusion, blood pressure, and infarct size were measured and cardiac function was evaluated by a Millar catheter. FAMP significantly improved stroke volume, cardiac output, left ventricular ejection fraction, and infarct size. FAMP significantly preserved cytochrome C in the mitochondrial fraction and inhibited its release into the cytosolic fraction in the heart, but did not significantly reduce mRNA levels of monocyte chemoattractant protein-1 or interluekin-6. In a TdT-mediated dUTP nick end labeling (TUNEL) assay, FAMP significantly suppressed the appearance of TUNEL-positive nuclear. We also performed same experiments with endothelial nitric oxide synthase-knockout (eNOS-KO) mice and FAMP-induced improvements of cardiac function were not observed in eNOS-KO mice.

Conclusions

FAMP activated HDL-functionality and improved cardiac function in a model of myocardial IRI. It may have anti-apoptotic effects by protecting mitochondria through a NO pathway as a pleiotropic effect.