Ablation of periostin inhibits post-infarction myocardial regeneration in neonatal mice mediated by the phosphatidylinositol 3 kinase/glycogen synthase kinase 3β/cyclin D1 signalling pathway

Abstract

AimsTo resolve the controversy as to whether periostin plays a role in myocardial regeneration after myocardial infarction (MI), we created a neonatal mouse model of MI to investigate the influence of periostin ablation on myocardial regeneration and clarify the underlying mechanisms.Methods and resultsNeonatal periostin-knockout mice and their wildtype littermates were subjected to MI or sham surgery. In the wildtype mice after MI, fibrosis was detectable at 3 days and fibrotic tissue was completely replaced by regenerated myocardium at 21 days. In contrast, in the knockout mice, significant fibrosis in the infarcted area was present at even 3 weeks after MI. Levels of phosphorylated-histone 3 and aurora B in the myocardium, detected by immunofluorescence and western blotting, were significantly lower in knockout than in wildtype mice at 7 days after MI. Similarly, angiogenesis was decreased in the knockout mice after MI. Expression of both the endothelial marker CD-31 and α-smooth muscle actin was markedly lower in the knockout than in wildtype mice at 7 days after MI. The knockout MI group had elevated levels of glycogen synthase kinase (GSK) 3β and decreased phosphatidylinositol 3-kinase (PI3K), phosphorylated serine/threonine protein kinase B (p-Akt), and cyclin D1, compared with the wildtype MI group. Similar effects were observed in experiments using cultured cardiomyocytes from neonatal wildtype or periostin knockout mice. Administration of SB216763, a GSK3β inhibitor, to knockout neonatal mice decreased myocardial fibrosis and increased angiogenesis in the infarcted area after MI.ConclusionAblation of periostin suppresses post-infarction myocardial regeneration by inhibiting the PI3K/GSK3β/cyclin D1 signalling pathway, indicating that periostin is essential for myocardial regeneration.

Periostin as a novel biomarker of cardiovascular disease: A systematic evidence landscape of preclinical and clinical studies

“…Furthermore, periostin also expressed myofibroblast in adult heart causes cardiac remodeling . In line with previous findings, neonatal mouse MI model also showed significantly increased mRNA expression of periostin at 1, 3, and 7 days after MI …”

“…There are several studies that have suggested that measurement of periostin may be of prognostic value. Such an association has been reported in CAD, HF, MI, and CVDs . In contrast, other study suggested that systemic periostin levels are largely determined by underlying pathogenesis of variety of cancer and allergic diseases, including asthma rather than cardiac function, and that prognostic significance does not remain after adjustment for underlying cardiac function .…”

“…25 In line with previous findings, neonatal mouse MI model also showed significantly increased mRNA expression of periostin at 1, 3, and 7 days after MI. 26 Additionally, in MI model of mouse, periostin acts similar as TGF-1 in mouse heart that affects myocardial fibrosis. 27 A transcriptional profiles of mice with HF identified a potential co-regulated gene as periostin, which is linked to the development of HF.…”

Epicardial therapy with atrial appendage micrografts salvages myocardium after infarction

“…Our findings demonstrate increased angiogenesis, vasculogenesis, and widespread prosurvival changes in the myocardium, which indicate induction of a protective and restorative myocardial environment by AAMs. Interestingly, our results from proteomics showed significantly increased expression levels of the cardiomyocyte mitogen and matricellular protein POSTN (33,34) in both the subtransplant and remote septal zones, thus further strengthening the cellular and molecular mechanisms behind the observed functional improvement after AAM patch transplantation.…”

“…However, in the AAM and ECM patch groups, the fall in LVEF seemed considerably smaller in magnitude than that observed in the MI group. The acute declines in LVEF at one-week time-point postoperatively in AAM patch, ECM patch and MI groups were as follows: 18.03 (from 54.49±2.93% to 36.69±2.56%), 19.77 (from 52.15±3.10% to 32.38±2.96%) and 34.94 percent points (from 58.72±2.58% to 23.78±3.16%), respectively, with significant difference perceptible only between AAM patch and MI groups. However, since prevention of acute HF seemed evident in both patch groups, we hypothesize a considerable protective effect to occur by direct mechanical support, i.e.…”