Periostin peptide affects fibrosis in the myocardium.

<p>Periostin peptide affects fibrosis in the myocardium.</p

Study design: 20 kg female Yorkshire pigs underwent experimental MI and received epicardial control gelfoam (Ctr.) or periostin peptide gelfoam (PN) 2 days later. PN (<i>n</i> = 7); Ctr (<i>n</i> = 6).

<p>Study design: 20 kg female Yorkshire pigs underwent experimental MI and received epicardial control gelfoam (Ctr.) or periostin peptide gelfoam (PN) 2 days later. PN (<i>n</i> = 7); Ctr (<i>n</i> = 6).</p

Periostin peptide-treated animals have smaller infarct scars and have myocardial strips.

<p>(<b>a, b</b>) Quantification of scar volume by delayed enhancement (DE) MRI imaging 12 weeks after implantation of periostin peptide or control gelfoam. Representative examples showing DE in pink (<b>a</b>) and quantification as percentage of LV myocardium show smaller scar areas in periostin peptide-treated animals (<b>b</b>). (<b>c, d</b>) Quantification of scar volume by tetrazolium chloride (TTC) staining. Representative slabs of the left ventricle (<b>c</b>) and quantification (<b>d</b>) show smaller scar areas in periostin peptide-treated animals; Scale bars, 1 cm. Myocardial tissue was only detectable in the scar area of treated animals (<b>e, f</b>). The heart to body weight ratio remained unaffected, (<b>g</b>), while the expansion index was increased in swine receiving periostin (<b>h</b>). Statistical significance tested with t-test (b, d). Scale bars, 5 mm (e), 1 cm (c). PN (<i>n</i> = 7); Ctr (<i>n</i> = 6).</p

Periostin peptide improves vascularization in the peri-infarct area.

<p>An increase in CD31 positive and vWF positive endothelial cells is detected 3 months post-periostin treatment in the peri-infarcted area. Quantification reveals a significantly increase capillary density compared to control animals (P<0.05). Blue, DAPI-stained nuclei; red, alpha-sarcomeric actin; green, CD31/von-Willebrand-factor (vWf).</p

Periostin improves regional function.

<p>Analysis of regional function by strain analysis. (<b>a</b>) Example of division of mid-ventricular short-axis image into six segments to determine regional strain. (<b>b</b>) Representative example of segmental circumferential strain before initiation of therapy shows lack of contractility in infarcted anterior segment (yellow line, designated A). (<b>c</b>) Strain analysis after combination of infarcted segments (MA+MAS) and non-infarcted segments (MIS+MI+ML+MAL). Ctr., control hearts receiving gelfoam with buffer (<i>n</i> = 6); PN, hearts receiving gelfoam with periostin peptide (<i>n</i> = 7). Statistical comparison between control and periostin peptide groups by t-test (a–e, * <i>P</i><0.05), and two-way ANOVA.</p

Adult cardiac fibroblast proliferation is moderately increased after periostin stimulation.

<p>(<b>a</b>) The effect of periostin on cell proliferation was quantified by BrdU incorporation using a colorimetric detection assay. At 0.5 and 1 μg/ml concentration, periostin treatment results in statistically significant increase in proliferation (p = 0.01 and 0.02 respectively). Culture with 10% FBS resulted in robust proliferation. (* P<0.05, ** P<0.01 to Control) (<b>b</b>) Adult cardiac fibroblasts with (0.5 μg/ml) or without stimulation by periostin.</p

Periostin peptide induces sustained functional improvements after MI.

<p>Periostin peptide induces sustained functional improvements after MI.</p

Periostin peptide induces cardiomyocyte proliferation after MI.

<p>Confocal images of representative sections from infarcted hearts, one week (<b>a</b>) and three months (<b>b</b>) after MI in vehicle-treated and Periostin-treated animal groups. Frozen sections were stained with Aurora B, Ki67, phospho-histone-H3 (P-H3), and alpha-sarcomeric actin. Blue, DAPI-stained nuclei; red, Aurora B, Ki67, P-H3; green, alpha-sarcomeric actin. A global increase in proliferation expression markers was detected in the epicardial zone of the Periostin treated pigs, 1 week post-MI. Aurora B and P-H3 expression markers were also detected 3 months after periostin treatment.</p