Study On Relationship Between Hypoxia-inducible Factor1and Cardiovascular Disease

Part I The Relationship Between serum hypoxia-inducible factor la and Coronary Artery Calcification in Uncomplicated type2Diabetic patientsBackground:Hypoxia-inducible factor1(HIF-1), as master regulators of oxygen homeostasis, a heterodimers consists of the subunits HIF-1α and HIF-1β, was implicated in calcification of cartilage and vasculature. The goal of this study was to determine the relationship of serum HIF-1α with coronary artery calcification (CAC) in patients with type2diabetes.Methods:The subjects were405asymptomatic patients with type2diabetes mellitus, included262males and143females with a mean (±SD) age of51.3±6.4years old. Serum levels of HIF-1α and interleukin-6(IL-6) were measured by ELISA. CAC scores were assessed by a320-slice CT scanner. The subjects were divided into4quartiles depending on serum HIF-1α levels.Results:The average serum HIF-1α level was184.4±66.7pg/ml.AmongpatientswithhigherCAC scores, HIF-1α levels were also significantlyincreased (P<0.001). HIF-1α levels positively correlated withCRP, IL-6, UKPDS riskscore, HbAlc, FBG and CACS, but were not correlated with diabetesduration, age and LDL. According tomultivariate logic analyses, HIF-la levels still significantly independent predict the presence of CAC. Receiver-operating characteristic curve analysis showed that serum HIF-la level can predict the extent of CAC, but the specificity was lower than the traditional risk factors UKPDS and HbAlc.Conclusions:As a marker of hypoxia, serum HIF-la level may be an independent risk factor for presence of CAC. These findings indicate that elevated serum HIF-la may be involved in vascular calcification in patients with type2diabetes mellitus. Part II Relationship betweenHIF-laexpression andcardiac functionamongpatients with heart failureObjective:Hypoxia-inducible factor1(HIF-1)mediates many important physiologicalreactions athypoxia situation as a transcriptionfactor. Because of myocardialhypoxia,patients with heart failure caninduceover expressionofHIF-1in vivo. In the absence of hemodynamic or neurohormonal stimuli, hypoxia directly enhances the synthesis and secretion of B-type natriuretic peptide (BNP) in ventricular myocytes, through a HIF-la dependent mechanism. Thus, we designed the first clinical study in order to evaluate the expression of HIFla in patients with heart failure and to determine its relationship with the BNP. Methods:76subjects with congestive heart failure were consecutively enlisted, included47acute left heart failure patients. The participants mean age were73.4±13.4years old. Serum levels of HIF-1α and BNP were measured by ELISA. Patients were divided into two groups according to their cardiac function and then to carry out statistical analysis.Results:The average serum HIF-la level was2.83±0.52ng/ml. The NYHA Ⅲ patient’s serum HIF-1αlevels were2.67±0.48ng/ml. The NYHA Ⅳ patient’s serum HIF-lalevels were2.95±0.52ng/ml. A statistically significant differencebetween two groups(P=0.018). Inpatients withacuteleftheart failure, the serum HIF-lalevels were also significantlyhigher thanin patientswith chronic heart failure (3.02±0.44VS2.51±0.49ng/ml, P<0.01). Serum HIF-la levels positively correlated with SPO2, cardiac function and acuteleftheart failure, but were not correlated with age, SBP, DBP, BNP and TNI. According tomultivariate logic analyses, HIF-1α levels cannot independently predicts the cardiac function of heart failure patients.Conclusions:Atthe peripheral bloodcirculation ofpatients with heart failure, wefirstdiscovered the existence ofHIF-lawhichoriginally only exists in the intracellular. In ourstudy population,although theserumlevels ofHIF-la was related with cardiacfunction in patients with heart failure, but was notan independent predictorof cardiac function.