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Apoptosis is involved in both acute and chronic loss of cardiomyocytes after myocardial infarction (MI). To date, the pathophysiological significance of an apoptotic transcriptional profile activated in the post-ischemic remodeled myocardium, in the absence of hemodynamic factors secondary to left ventricular (LV) dysfunction, still remains to be determined. The mRNA expression of pro- and anti-apoptotic factors was determined in a swine model of non-reperfused MI with preserved LV ejection fraction. The extent of cell death was evaluated by histological analysis. Male adult farm pigs with MI (n=5), induced by permanent surgical ligation of the left anterior descending coronary artery and sham-operated adult farm pigs as control (n=7) were studied. Tissue samples were collected from the border (BZ) and remote zone (RZ) of the infarcted area to identify possible regional effects. After 4 weeks post-MI, the infarct size was 13±1% of the LV wall mass in absence of contractile dysfunction. In BZ, there was increased mRNA expression of Casp-3 (BZ vs Controls: 0.51±0.15 vs 1.39±0.04, p<0.001), a significant decrease in Bcl-2 (by 63%), associated with an increase in apoptotic cells, as revealed by TUNEL staining and cleaved-Casp-3 presence. In contrast, in the RZ there was a significant reduction of pro-apoptotic factors compared to BZ (by 80% for Casp-3), in presence of scattered apoptotic cells, increased gene expression of Hsp72 (1.82±0.21 vs 1.34±0.08, p=0.037) and iNOS (1.51±0.14 vs 1.19±0.05, p<0.05) compared to control. In conclusion, the LV distribution of apoptotic transcriptional profile revealed that apoptotic cell death is highly detectable in BZ, possibly explaining the local abnormalities of myocardial cell survival in a porcine model of MI with normal overall function., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The role of myocardial apoptosis during the development of heart failure (HF), in the absence of coronary artery stenosis, is still debated. The aim of the study was to evaluate whether (similar to functional impairment) the activation of myocardial apoptosis follows a regional pattern in an established model of pacing-induced HF. HF was induced in adult male minipigs by rapid and sustained left ventricular (LV) epicardial pacing (n=8; n=5 healthy controls). Progressive regional derangement of the contractile function and perfusion was assessed by magnetic resonance imaging as LV end-systolic wall thickening (LVESWT) and relative upslope of signal intensity (LVRUSI, %) in the anterior/anterior-lateral (pacing site, PS) and infero-septal LV region (opposite site, OS). LV tissue from PS and OS was analyzed for biomarkers of cell apoptosis and injury. After 21 days of LV pacing, LVESWT was lower in the PS compared to OS (7.6±3.7 vs 24.16±3.6%, p<0.05), and LV ejection fraction was 24.0±3.7 (p<0.05 vs control). The mRNA expression of caspase (Casp)-3 was significantly higher in the PS of HF hearts than in controls (1.28±0.125 vs 0.82±0.10), but not Casp-9. Bcl-2 and Hsp72 expression was significantly increased in PS compared to control (0.90±0.60 vs 0.63±0.033; 0.72±0.10 vs 0.28±0.098), in the presence of a TNF-α level increased by 50.7%. The regional myocardial apoptotic index, assessed by TUNEL, was unchanged in HF. In conclusion, the activators and inhibitors of cell apoptosis are equally expressed without affecting the survival of cardiomyocytes and the magnitude of regional myocardial dysfunction during development of non-ischemic HF., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

In humans, the Apelin gene is located on chromosome Xq25-26.1 and it encodes a 77-aminoacid prepropeptide. Considerable sequence homology exists across different mammalian species. Apelin is emerging as an important regulator of cardiovascular homeostasis but, at present, few data from humans are available and further studies are necessary to better define its role in cardiovascular pathophysiology. The role and function of Apelin in cardiovascular system could be reliably investigated in experimental models devoid of confounding effects reflecting only the natural history of the disease. The pig constitutes a model largely used in experimental pathology where it has a central role in "in vivo" clinical settings. Sus Scrofa genoma is not completely sequenced and Apelin gene is still lacking. Aim of this study was to sequence the Apelin in Sus Scrofa for future applications to molecular biology studies. Using the guanidinium thyocyanate-phenol-chloroform method, we extracted total RNA from samples obtained from heart of mouse and from atrium and ventricle of normal pigs. Pig Apelin mRNA was sequenced using polymerase chain reaction primers designed from mouse consensus sequences. A partial sequence of Sus Scrofa Apelin mRNA, 1-201 pb, was submitted to GenBank (accession number FJ362603). The bands obtained from pig cardiac tissue shared a 99% sequence identity with Mus musculus and 90% with Rattus norvegicus. The knowledge of Apelin sequence can be an useful starting point for future studies devoted to better understand the possible alterations of Apelin mRNA expression in different cardiac diseases.

Background: Overexpression of heat shock proteins (Hsps) is associated to myocardial protection and it has been suggested that they could be a marker of cardiac preservation in conditions such as extracorporeal circulation. Aim of this study was to evaluate if cardioplegic arrest can modify the expression of Hsps in the heart and if this alteration is associated to cardiac preservation., Method: The levels of Hsp 27, Hsp 60, and both the constitutive and the inducible form of Hsp 70 were measured in the cardiac tissue from right atrium of pediatric patients before and after aortic cross-clamping (ACC) during cardiopulmonary bypass surgery for correction of congenital heart disease (n=20). The quantitative evaluation of Hsps was made by Western blotting analysis after tissue extraction and protein separation. Hsp 72 mRNA expression was also evaluated in pre- and post-ACC samples of eight subjects by semiquantitative RT-PCR. Peripheral levels of Troponin I, Myoglobin, LDH, CK, CK-MB were measured in basal conditions and at 12 and 24h after cardiosurgery as markers of heart damage., Results: The cardioplegic arrest did not significantly modify the mean levels of all the Hsps measured. Hsp 72 levels increased after cardioplegia in the 40% of the patients and all Hsps in the 28% of subjects. The patients whose levels of Hsps are increased after cardioplegia are associated with lower post-surgery concentrations of all the markers of cardiac injury., Conclusions: This observation suggests a relationship between the increase of Hsps and the reduction of cardiac injury.