Author + information
- Angelos Tsipis2,2,
- Anna Maria Athanassiadou1,
- Emmanouil Petrou2,
- Dimitrios Miliopoulos2,
- Aggeliki Gkouziouta2,
- Pauline Athanassiadou1 and
- Polixeni Nikolopoulou1
HIF1-α is a transcription factor, sensitive to hypoxia and is up-regulated in regions of myocardial ischemia. HIF1-α regulates several pathways critical for cellular response to hypoxia. Under hypoxia, HIF1-α protein rapidly induces the expression of genes that increase the oxygen availability to cells such as the expression of vascular endothelial growth factor (VEGF). HIF1-α also regulates the expression of a battery of genes involved in the promotion or inhibition of apoptotic pathway. The aim of the present study was to investigate the expression of HIF1-α in myocardial infarction and the relation with VEGF and the apoptotic proteins.
We studied myocardial samples of hearts with histologic findings of acute myocardial infarction (group A, n=100), old myocardial infraction (group B, n=100) and myocardial samples of normal heart (control group, n=20). An immunohistochemical method was performed with the use of HIF1-α, VEGF, Bax, Bcl-2 antibodies, in order to investigate the expression of HIF1-α and apoptosis-related proteins bax, bcl-2 in ischemic cardiac disorders.
HIF1-α expression was intensive at the risk areas of samples with acute myocardial infarction. In old myocardial infraction the HIF1-α expression decreased and the positive samples demonstrated weak staining. VEGFis expressed in cardiomyocytes at the risk areas of acute myocardial infarction in 80% of cases. High concordance of HIF1-α and VEGF expression was detected (71,5% of cases, p = 0.020). Bcl-2 positive expression was moderate at the risk areas in 75% of samples with acute myocardial infarction. In old myocardial infraction the bcl-2 positive samples demonstrated weak staining as in the control group. Bax staining was weak in 80% of samples with acute myocardial infraction and intensive in 60% of samples with old myocardial infraction. Bax positive expression was weak in 50% of samples of the control group.
Increased levels of HIF1-α were associated with intense expression of antiapoptotic bcl-2 protein in acute myocardial infraction. Decreased levels of HIF1-α and intensive expression of proapoptotic bax were found in cases of old myocardial infraction. The decreased expression of HIF1-α is associated with the progressive loss of myocytes by apoptosis. The increased expression of HIF1-α and bcl-2 in acute myocardial infraction represents a possible compensatory mechanism of salvaged myocytes. The prevalence of the apoptotic mechanism or this of compensatory antiapoptotic may influence the progression of heart failure.