PR-39, a proline/arginine-rich antimicrobial peptide, exerts cardioprotective effects in myocardial ischemia-reperfusion.

Abstract

OBJECTIVE:

PR-39, a proline/arginine-rich antimicrobial peptide, has been shown to inhibit the NADPH oxidase activity of polymorphonuclear leukocytes (PMNs) by blocking assembly of this enzyme. We hypothesized that PR-39 could attenuate PMN-induced cardiac dysfunction by suppression of superoxide production.

METHODS:

We examined the effects of PR-39 in isolated ischemic (20 min) and reperfused (45 min) rat hearts administered PMNs at the onset of reperfusion.

RESULTS:

PR-39 (4 or 10 microg/ml) given i.v. 30 min prior to ischemia-reperfusion (I-R) significantly improved left ventricular developed pressure (LVDP, P<0.01) and the maximal rate of development of LVDP (i.e. +dP/dt max, P<0.01) compared to I-R hearts obtained from rats given 0.9% NaCl. PR-39-treated PMNs (10 microg/ml) also significantly attenuated cardiac contractile dysfunction after I-R (P<0.01). Superoxide release was significantly reduced (P<0.01) in N-formylmethionyl-leucylphenylalanine stimulated PMNs pretreated with 4 or 10 microg/ml PR-39. PR-39 also significantly attenuated P-selectin expression on the rat coronary microvascular endothelium and CD18 upregulation in rat PMNs. In addition, PR-39 significantly reduced PMN vascular adherence and infiltration into the post-ischemic myocardium.

CONCLUSION:

These results provide evidence that PR-39 significantly attenuates PMN-induced cardiac contractile dysfunction in the I-R rat heart at least in part via suppression of superoxide release. This cardioprotection occurred both by inhibition of PMN and endothelial NADPH oxidase.

• Authors: Y Ikeda, L H Young, R Scalia, C R Ross, A M Lefer
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 49 Issue 1 Pg. 69-77 (Jan 2001) ISSN: 0008-6363 [Print] England
• PMID: 11121797 (Publication Type: Journal Article)

Chemical References

• Anti-Bacterial Agents
• Antimicrobial Cationic Peptides
• CD18 Antigens
• P-Selectin
• Superoxides
• PR 39

Topics

• Animals
• Anti-Bacterial Agents (therapeutic use)
• Antimicrobial Cationic Peptides (therapeutic use)
• CD18 Antigens (metabolism)
• Endothelium, Vascular (metabolism, pathology)
• Male
• Myocardial Contraction (drug effects)
• Myocardial Reperfusion Injury (metabolism, pathology, prevention & control)
• Myocardium (metabolism)
• Neutrophils (physiology, transplantation)
• Organ Culture Techniques
• P-Selectin (metabolism)
• Rats
• Rats, Sprague-Dawley
• Superoxides (metabolism)