Y. Ikeda et al., PR-39, a proline/arginine-rich antimicrobial peptide, exerts cardioprotective effects in myocardial ischemia-reperfusion, CARDIO RES, 49(1), 2001, pp. 69-77
Citations number
38
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Objective: PR-39, a proline/arginine-rich antimicrobial peptide, has been s
hown to inhibit the NADPH oxidase activity of polymorphonuclear leukocytes
(PMNs) by blocking assembly of this enzyme. We hypothesized that PR-39 coul
d attenuate PMN-induced cardiac dysfunction by suppression of superoxide pr
oduction. Methods: We examined the effects of PR-39 in isolated ischemic (2
0 min) and reperfused (45 min) rat hearts administered PMNs at the onset of
reperfusion. Results: PR-39 (4 or 10 mug/ml) given i.v. 30 min prior to is
chemia-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% NaC
l. PR-39-treated PMNs (10 mug/ml) also significantly attenuated cardiac con
tractile dysfunction after I-R (P<0.01). Superoxide release was significant
ly reduced (P<0.01) in N-formylmethionyl-leucylphenylalanine stimulated PMN
s pretreated with 4 or 10 mug/ml PR-39. PR-39 also significantly attenuated
P-selectin expression on the rat coronary microvascular endothelium and CD
18 upregulation in rat PMNs. In addition, PR-39 significantly reduced PMN v
ascular adherence and infiltration into the post-ischemic myocardium. Concl
usion: These results provide evidence that PR-39 significantly attenuates P
MN-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. (C) 2001 Elsevier
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