Augmented Cardiac Hypertrophy in Response to Pressure Overload in Mice Lacking the Prostaglandin I ₂ Receptor

Abstract

Background-In the heart, the expressions of several types of prostanoid receptors have been reported. However, their roles in cardiac hypertrophy in vivo remain unknown. We intended to clarify the roles of these receptors in pressure overload-induced cardiac hypertrophy using mice lacking each of their receptors. Methods and Results-We used a model of pressure overload-induced cardiac hypertrophy produced by banding of the transverse aorta in female mice. In wild-type mice subjected to the banding, cardiac hypertrophy developed during the observation period of 8 weeks. In mice lacking the prostaglandin (PG) I 2 receptor (IP Ϫ/Ϫ ), however, cardiac hypertrophy and cardiomyocyte hypertrophy were significantly greater than in wild-type mice at 2 and 4 weeks but not at 8 weeks, whereas there was no such augmentation in mice lacking the prostanoid receptors other than IP. In addition, cardiac fibrosis observed in wild-type hearts was augmented in IP Ϫ/Ϫ hearts, which persisted for up to 8 weeks. In IP Ϫ/Ϫ hearts, the expression level of mRNA for atrial natriuretic peptide, a representative marker of cardiac hypertrophy, was significantly higher than in wild-type hearts. In vitro, cicaprost, an IP agonist, reduced platelet-derived growth factor-induced proliferation of wild-type noncardiomyocytes, although it could not inhibit cardiotrophin-1-induced hypertrophy of cardiomyocytes. Accordingly, cicaprost increased cAMP concentration efficiently in noncardiomyocytes. Conclusions-IP

Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and function

“…Here, deletion of CM-COX-2 resulted in interstitial and perivascular fibrosis and both features were augmented as cardiac function recovered over time following aortic banding. The morphological response to banding was reminiscent of that observed in an earlier study of older (Ͼ 24 weeks) IP-deleted mice in whom cardiac function was not reported (36). As in the present study, formation of PGI 2 was not altered 1 week after banding.…”

Iloprost reverses established fibrosis in experimental right ventricular failure

“…FRANCOIS et al [46] and HARA et al [47] have demonstrated that transgenic mice lacking the IP receptor develop significant cardiac fibrosis, whereas mice lacking other prostaglandin receptors, such as EP [2][3][4], FP or TP, do not [47]. While these studies demonstrate a protective role for prostacyclins against cardiac fibrosis, it has not been investigated whether treatment with prostacyclins would be sufficient to reverse established fibrosis.…”

Eicosapentaenoic Acid (EPA) Reduces Cardiovascular Events: Relationship with the EPA/Arachidonic Acid Ratio

“…In active-phase patients with angina, platelet IP is reduced and the inhibitory effects of PGI2 on platelet aggregation are weakened, whereas the IP count is recovered in inactive-phase patients 87) . In IP-deficient mice, the size of the myocardial infarction caused by coronary artery ligation is significantly increased compared to that observed in wild-type mice, suggesting that PGI2 protects the myocardium from ischemia and reperfusion injury 88) . Meanwhile, the administration of hp-EPA-E (Epadel ® ) reduces neutrophil infiltration in ischemic regions caused by myocardial ischemia following left circumflex coronary artery ligation and reperfusion in pigs, thus helping to maintain the myocardial eNOS activity in the ischemic myocardium 89) .…”