Can HIF-1 Alpha (Hypoxia- inducible factor-1 alpha) be a New Cardiac Hypoxia Marker in Acute Coronary Ischemia?

Abstract

Objective:Hypoxia- inducible factor-1 alpha (HIF-1 alpha) is a gene protein whose activation is a primary defensive mechanism against tissue hypoxia. It is the main regulator of cellular oxygen delivery and consumption. HIF-1 alpha activity is increased in tissue ischemia and this induces the angiogenic growth factor release that is needed for vascular remodeling and collateral formation, and contributes to improvement in cardiac functions. In this study, it was aimed to measure HIF-1 alpha levels in acute cardiac ischemia, to evaluate its relationship with inflammatory and biochemical parameters, and to investigate HIF-1 alpha as a possible cardiac hypoxia marker.Method:First 31 patients who were admitted to coronary ICU with Acute Coronary syndrome (ACS) diagnosis in March 2018 were included in the study and 22 (14 female, 8 male) age-gender-matched healthy control group were included in the study. In both case (coronary ICU patient) and control groups), after 12-hour hunger, venous blood samples were taken to measure HIF-1 alpha, biochemical parameters [glucose, urea, creatinine, uric acid, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT)], hemoglobin, platelets, platelet parameters [mean platelet volume (MPV), procalcitonin (PCT), platelet distribution width (PDW)], inflammatory parameters [C-reactive protein (CRP), neutrophil/lymphocyte ratio] and homocysteine levels. Results were evaluated using SPSS 22.0 program.Results:Thirty one patients in the case group and 22 patients in the control group, totally 53 patients, were included in the study. The mean age was 68.2±14.3 years in the case group and 63.6±9.6 years in the control group. Age and gender distribution, glucose, AST, ALT, PLT, MPV, PCT, PDW and homocysteine levels did not show any significant difference in the case and control groups (p>0.05). Urea, creatinine, uric acid, GGT, CRP, hemoglobin, and N/L levels were significantly higher in the case group when compared to the control group (p˂0.05). Although HIF-1 alpha level was higher in the case group when compared to the control group, it was not statistically significant.Conclusion:There are studies showing the role of HIF-1 alpha in myocardial remodeling, angiogenesis and cardiac function improvement. In hypoxic conditions, increase in HIF-1 alpha improves tissue oxygenation. Same adaptive mechanism was not observed in our study. We think the reasons underlying this situation could be that in our patients, ischemia was localized but not generalized like in hypoxia, medical therapy was started immediately after admission (e.g.oxygen, nitrates, acetyl salicylic acid, heparin), the patients were normotensive under treatment, they did not have anemia, and they were given specific medications (e.g. ACE inhibitors, ARB) that could decrease oxidative distress. New treatment modalities to protect the heart from ischemic damage will be available when our knowledge about cardiac functions at different oxygen levels and factors affecting them increases. Then, HIF-1 alpha might be re-evaluated as a potential cardiac hypoxia marker.

Keywords

• coronary ischemia
• hif-1 alpha
• hypoxia