Apoptotic transcriptional profile remains activated in late remodeled left ventricle after myocardial infarction in swine infarcted hearts with preserved ejection fraction

作者：Prescimone Tommaso; Lionetti Vincenzo; Cabiati Manuela; Caselli Chiara; Aquaro Giovanni D; Matteucci Marco; Del Ry Silvia; Giannessi Daniela^*

来源：Pharmacological Research, 2013, 70(1): 41-49.

DOI：10.1016/j.phrs.2012.12.007

• Apoptosis
• Myocardial infarction
• Border zone
• Remote zone
• Caspases
• Heat shock proteins

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.

• 出版日期2013-4